Joel N Hirschhorn

Summary

Affiliation: Harvard University
Country: USA

Publications

  1. ncbi request reprint Genetic approaches to studying common diseases and complex traits
    Joel N Hirschhorn
    Program in Genomics and Division of Endocrinology, Children s Hospital, Boston, Massachusetts 02115, USA
    Pediatr Res 57:74R-77R. 2005
  2. ncbi request reprint Genome-wide association studies for common diseases and complex traits
    Joel N Hirschhorn
    Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02139, USA
    Nat Rev Genet 6:95-108. 2005
  3. ncbi request reprint Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels
    Richa Saxena
    Broad Institute of Harvard and Massachusetts Institute of Technology MIT, Cambridge, MA 02142, USA
    Science 316:1331-6. 2007
  4. ncbi request reprint Association of common variation in the HNF1alpha gene region with risk of type 2 diabetes
    Wendy Winckler
    Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA
    Diabetes 54:2336-42. 2005
  5. ncbi request reprint Association studies of BMI and type 2 diabetes in the neuropeptide Y pathway: a possible role for NPY2R as a candidate gene for type 2 diabetes in men
    Catarina D Campbell
    Program in Genomics and Division of Endocrinology, Children s Hospital, Boston, Massachusetts 021115, USA
    Diabetes 56:1460-7. 2007
  6. ncbi request reprint The Krüppel-like factor 11 (KLF11) Q62R polymorphism is not associated with type 2 diabetes in 8,676 people
    Jose C Florez
    Simches Research Building, CPZN 6820, Diabetes Unit Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA 02114, USA
    Diabetes 55:3620-4. 2006
  7. ncbi request reprint Transferability of tag SNPs in genetic association studies in multiple populations
    Paul I W de Bakker
    Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Seven Cambridge Center, Cambridge, Massachusetts, 02142, USA
    Nat Genet 38:1298-303. 2006
  8. ncbi request reprint Association testing of variants in the hepatocyte nuclear factor 4alpha gene with risk of type 2 diabetes in 7,883 people
    Wendy Winckler
    Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA
    Diabetes 54:886-92. 2005
  9. ncbi request reprint Common variants in the ENPP1 gene are not reproducibly associated with diabetes or obesity
    Helen N Lyon
    Division of Genetics, Children s Hospital Boston, Enders 561, 300 Longwood Ave, Boston, MA 02115, USA
    Diabetes 55:3180-4. 2006
  10. pmc Association studies of common variants in 10 hypogonadotropic hypogonadism genes with age at menarche
    Zofia K Z Gajdos
    Program in Genomics and Division of Endocrinology, Children s Hospital, and Department of Genetics, Harvard Medical School, 300 Longwood Avenue, Boston, Massachusetts 02115, USA
    J Clin Endocrinol Metab 93:4290-8. 2008

Detail Information

Publications113 found, 100 shown here

  1. ncbi request reprint Genetic approaches to studying common diseases and complex traits
    Joel N Hirschhorn
    Program in Genomics and Division of Endocrinology, Children s Hospital, Boston, Massachusetts 02115, USA
    Pediatr Res 57:74R-77R. 2005
    ..Finally, population genetic methods, including searching for genes under selection, may provide clues to the location of the genes for common disease and complex traits...
  2. ncbi request reprint Genome-wide association studies for common diseases and complex traits
    Joel N Hirschhorn
    Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02139, USA
    Nat Rev Genet 6:95-108. 2005
    ..Genome-wide association studies will soon become possible, and could open new frontiers in our understanding and treatment of disease. However, the execution and analysis of such studies will require great care...
  3. ncbi request reprint Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels
    Richa Saxena
    Broad Institute of Harvard and Massachusetts Institute of Technology MIT, Cambridge, MA 02142, USA
    Science 316:1331-6. 2007
    ..The discovery of associated variants in unsuspected genes and outside coding regions illustrates the ability of genome-wide association studies to provide potentially important clues to the pathogenesis of common diseases...
  4. ncbi request reprint Association of common variation in the HNF1alpha gene region with risk of type 2 diabetes
    Wendy Winckler
    Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA
    Diabetes 54:2336-42. 2005
    ....
  5. ncbi request reprint Association studies of BMI and type 2 diabetes in the neuropeptide Y pathway: a possible role for NPY2R as a candidate gene for type 2 diabetes in men
    Catarina D Campbell
    Program in Genomics and Division of Endocrinology, Children s Hospital, Boston, Massachusetts 021115, USA
    Diabetes 56:1460-7. 2007
    ..73 x 10(-4), OR = 1.36) and not in women. Variation in this pathway likely does not have a major influence on BMI, although small effects cannot be ruled out; NPY2R should be considered a candidate gene for type 2 diabetes in men...
  6. ncbi request reprint The Krüppel-like factor 11 (KLF11) Q62R polymorphism is not associated with type 2 diabetes in 8,676 people
    Jose C Florez
    Simches Research Building, CPZN 6820, Diabetes Unit Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA 02114, USA
    Diabetes 55:3620-4. 2006
    ..We conclude that the KLF11 A347S and T220M mutations do not contribute to increased risk of diabetes in European-derived populations and that the Q62R polymorphism has, at best, a minor effect on diabetes risk...
  7. ncbi request reprint Transferability of tag SNPs in genetic association studies in multiple populations
    Paul I W de Bakker
    Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Seven Cambridge Center, Cambridge, Massachusetts, 02142, USA
    Nat Genet 38:1298-303. 2006
    ..These results demonstrate that the HapMap DNA samples can be used to select tags for genome-wide association studies in many samples around the world...
  8. ncbi request reprint Association testing of variants in the hepatocyte nuclear factor 4alpha gene with risk of type 2 diabetes in 7,883 people
    Wendy Winckler
    Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA
    Diabetes 54:886-92. 2005
    ....
  9. ncbi request reprint Common variants in the ENPP1 gene are not reproducibly associated with diabetes or obesity
    Helen N Lyon
    Division of Genetics, Children s Hospital Boston, Enders 561, 300 Longwood Ave, Boston, MA 02115, USA
    Diabetes 55:3180-4. 2006
    ..6 [0.42-0.88], P = 0.007). However, these findings are not supported by other studies. We did not observe a reproducible association between these three ENPP1 variants and BMI or type 2 diabetes...
  10. pmc Association studies of common variants in 10 hypogonadotropic hypogonadism genes with age at menarche
    Zofia K Z Gajdos
    Program in Genomics and Division of Endocrinology, Children s Hospital, and Department of Genetics, Harvard Medical School, 300 Longwood Avenue, Boston, Massachusetts 02115, USA
    J Clin Endocrinol Metab 93:4290-8. 2008
    ..Several genes have been identified that, when mutated, cause disorders of delayed or absent puberty such as hypogonadotropic hypogonadism (HH)...
  11. ncbi request reprint The ENPP1 K121Q polymorphism is associated with type 2 diabetes in European populations: evidence from an updated meta-analysis in 42,042 subjects
    Jarred B McAteer
    Diabetes Unit Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA 02114, USA
    Diabetes 57:1125-30. 2008
    ..We therefore conducted a new meta-analysis that includes novel unpublished data from the ENPP1 Consortium and recent negative findings from large association studies to address the contribution of K121Q to type 2 diabetes...
  12. pmc PNPLA3 variants specifically confer increased risk for histologic nonalcoholic fatty liver disease but not metabolic disease
    Elizabeth K Speliotes
    Department of Gastroenterology, Massachusetts General Hospital, Boston, MA 02114, USA
    Hepatology 52:904-12. 2010
    ..We did not observe any association of this variant with body mass index, triglyceride levels, high- and low-density lipoprotein levels, or diabetes (P > 0.05). None of the variants at the other 6 loci were associated with NAFLD...
  13. pmc An excess of risk-increasing low-frequency variants can be a signal of polygenic inheritance in complex diseases
    Yingleong Chan
    Department of Genetics, Harvard Medical School, Boston, MA 02115, USA Program in Medical and Population Genetics, Broad Institute, Cambridge, MA 02142, USA Department of Endocrinology, Boston Children s Hospital, Boston, MA 02115, USA
    Am J Hum Genet 94:437-52. 2014
    ..Thus, our method may also help guide the design of future genetic studies of various traits and diseases...
  14. ncbi request reprint A common genetic variant is associated with adult and childhood obesity
    Alan Herbert
    Department of Genetics and Genomics, Boston University Medical School, E613, 715 Albany Street, Boston, MA 02118, USA
    Science 312:279-83. 2006
    ..The obesity-predisposing genotype is present in 10% of individuals. Our study suggests that common genetic polymorphisms are important determinants of obesity...
  15. pmc Candidate gene association resource (CARe): design, methods, and proof of concept
    Kiran Musunuru
    Broad Institute, Cambridge, MA 02142, USA
    Circ Cardiovasc Genet 3:267-75. 2010
    ..The goals of CARe include the discovery of new variants associated with traits using a candidate gene approach and the discovery of new variants using the genome-wide association mapping approach specifically in African Americans...
  16. ncbi request reprint High-density haplotype structure and association testing of the insulin-degrading enzyme (IDE) gene with type 2 diabetes in 4,206 people
    Jose C Florez
    Diabetes Unit, Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA
    Diabetes 55:128-35. 2006
    ..Nominally significant differences in quantitative traits are consistent with statistical noise. We conclude that common genetic variation at IDE is unlikely to confer clinically significant risk of type 2 diabetes in Caucasians...
  17. pmc Use of weighted reference panels based on empirical estimates of ancestry for capturing untyped variation
    Matthew R L Egyud
    Children s Hospital, Boston, MA 02115, USA
    Hum Genet 125:295-303. 2009
    ....
  18. ncbi request reprint Evaluation of common variants in the six known maturity-onset diabetes of the young (MODY) genes for association with type 2 diabetes
    Wendy Winckler
    Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA
    Diabetes 56:685-93. 2007
    ..We conclude that although rare variants in these six genes explain most cases of MODY, common variants in these same genes contribute very modestly, if at all, to the common form of type 2 diabetes...
  19. pmc Assessing the phenotypic effects in the general population of rare variants in genes for a dominant Mendelian form of diabetes
    Jason Flannick
    1 Program in Medical and Population Genetics, Broad Institute of Harvard and Massachusetts Institute of Technology MIT, Cambridge, Massachusetts, USA 2 Department of Molecular Biology, Massachusetts General Hospital, Boston, Massachusetts, USA 3 Diabetes Unit, Massachusetts General Hospital, Boston, Massachusetts, USA 4
    Nat Genet 45:1380-5. 2013
    ..Accurate estimates of variant effect sizes from population-based sequencing are needed to avoid falsely predicting a substantial fraction of individuals as being at risk for MODY or other Mendelian diseases...
  20. ncbi request reprint Common single nucleotide polymorphisms in TCF7L2 are reproducibly associated with type 2 diabetes and reduce the insulin response to glucose in nondiabetic individuals
    Richa Saxena
    Program in Medical and Population Genetics, Broad Institute of Harvard and Massachusetts Institute of Technology, MA, USA
    Diabetes 55:2890-5. 2006
    ..003) but not with increased insulin resistance. These results suggest that TCF7L2 variants may act through insulin secretion to increase the risk of type 2 diabetes...
  21. pmc Association of common variants in NPPA and NPPB with circulating natriuretic peptides and blood pressure
    Christopher Newton-Cheh
    Center for Human Genetic Research, Massachusetts General Hospital, 55 Fruit Street, Boston, Massachusetts 02114, USA
    Nat Genet 41:348-53. 2009
    ..85-0.95, P = 2 x 10(-4), respectively). Common genetic variants at the NPPA-NPPB locus found to be associated with circulating natriuretic peptide concentrations contribute to interindividual variation in blood pressure and hypertension...
  22. doi request reprint Human fetal hemoglobin expression is regulated by the developmental stage-specific repressor BCL11A
    Vijay G Sankaran
    Division of Hematology Oncology, Children s Hospital Boston, Harvard Stem Cell Institute, Harvard Medical School, Boston, MA 02115, USA
    Science 322:1839-42. 2008
    ..BCL11A emerges as a therapeutic target for reactivation of HbF in beta-hemoglobin disorders...
  23. pmc Ultraconserved elements in the human genome: association and transmission analyses of highly constrained single-nucleotide polymorphisms
    Charleston W K Chiang
    Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA
    Genetics 192:253-66. 2012
    ..Our study also illustrated the importance of carefully modeling potential technical confounders when analyzing genotype data of rare variants...
  24. pmc Enhanced statistical tests for GWAS in admixed populations: assessment using African Americans from CARe and a Breast Cancer Consortium
    Bogdan Pasaniuc
    Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA
    PLoS Genet 7:e1001371. 2011
    ..Our methods and our publicly available software are broadly applicable to GWAS in admixed populations...
  25. ncbi request reprint Common genetic variation in eight genes of the GH/IGF1 axis does not contribute to adult height variation
    Guillaume Lettre
    Program in Medical and Population Genetics, Broad Institute of Harvard and Massachusetts Institute of Technology, Seven Cambridge Center, Cambridge, MA 02142, USA
    Hum Genet 122:129-39. 2007
    ....
  26. pmc Systematic evaluation of genetic variation at the androgen receptor locus and risk of prostate cancer in a multiethnic cohort study
    Matthew L Freedman
    Department of Genetics, Harvard Medical School, Massachusetts General Hospital, Boston, MA 02114, USA
    Am J Hum Genet 76:82-90. 2005
    ..A systematic approach that assesses both coding and noncoding genetic variation in large and diverse patient samples can help clarify hypotheses about association between genetic variants and disease...
  27. pmc Comprehensive association testing of common mitochondrial DNA variation in metabolic disease
    Richa Saxena
    Center for Human Genetic Research, Massachusetts General Hospital, Boston, 02114, USA
    Am J Hum Genet 79:54-61. 2006
    ..More generally, this comprehensive association-testing framework can readily be applied to other diseases for which mitochondrial dysfunction has been implicated...
  28. pmc The association of a SNP upstream of INSIG2 with body mass index is reproduced in several but not all cohorts
    Helen N Lyon
    Program in Genomics, Divisions of Genetics and Endocrinology, Children s Hospital, Boston, Massachusetts, USA
    PLoS Genet 3:e61. 2007
    ....
  29. pmc The efficacy of detecting variants with small effects on the Affymetrix 6.0 platform using pooled DNA
    Charleston W K Chiang
    Department of Genetics, Harvard Medical School, Boston, MA 02115, USA
    Hum Genet 130:607-21. 2011
    ..While our conclusions were based on the specific technology and study design we employed, the approach presented here will be useful for evaluating the utility of other or future genome-wide genotyping platforms in pooled DNA studies...
  30. ncbi request reprint Haplotype structures and large-scale association testing of the 5' AMP-activated protein kinase genes PRKAA2, PRKAB1, and PRKAB2 [corrected] with type 2 diabetes
    Maria W Sun
    Dept of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA
    Diabetes 55:849-55. 2006
    ..Several nominal associations of variants in PRKAA2 and PRKAB1 with BMI appear to be consistent with statistical noise...
  31. ncbi request reprint Common variation in BRCA2 and breast cancer risk: a haplotype-based analysis in the Multiethnic Cohort
    Matthew L Freedman
    The Broad Institute of MIT and Harvard, Cambridge, MA, USA
    Hum Mol Genet 13:2431-41. 2004
    ..However, a significant elevation in risk was observed among approximately 6% of women who carried a specific haplotype pattern and may harbor a susceptibility allele at the BRCA2 locus...
  32. pmc Simulation of Finnish population history, guided by empirical genetic data, to assess power of rare-variant tests in Finland
    Sophie R Wang
    Division of Endocrinology, Boston Children s Hospital, Boston, MA 02115, USA Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA Department of Genetics, Harvard Medical School, Boston, MA 02115, USA
    Am J Hum Genet 94:710-20. 2014
    ..As genetic studies probe sequence variation at greater depth in more diverse populations, our simulation approach provides a framework for evaluating various study designs for gene discovery. ..
  33. pmc Increased burden of cardiovascular disease in carriers of APOL1 genetic variants
    Kaoru Ito
    From the Department of Genetics, Harvard Medical School, Boston, MA K I, A G B, M G P, S R D, J N H, J G S, C S Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge K I, A G B, J F, G G, N G, S B G, C N C, S K, J N H, D M A, M R P, J G S, C S Center for Human Genetic Research, Massachusetts General Hospital, Boston J F, C N C, S K, D M A Division of Nephrology, Department of Medicine D J F, G G, M R P and Center for Vascular Biology Research, Department of Medicine D J F, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston
    Circ Res 114:845-50. 2014
    ..Approximately 14% of Americans with African ancestry carry 2 APOL1 risk alleles, accounting for the high chronic kidney disease burden in this population...
  34. pmc Identification of ten loci associated with height highlights new biological pathways in human growth
    Guillaume Lettre
    Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA
    Nat Genet 40:584-91. 2008
    ..These results expand the picture of the biological regulation of human height and of the genetic architecture of this classical complex trait...
  35. ncbi request reprint Association testing in 9,000 people fails to confirm the association of the insulin receptor substrate-1 G972R polymorphism with type 2 diabetes
    Jose C Florez
    Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA
    Diabetes 53:3313-8. 2004
    ..15 [1.05-1.26], P = 0.001). Despite genotyping 9,000 people and >95% power to reproduce the estimated OR from the recent meta-analysis, we were unable to replicate the association of the IRS-1 G972R polymorphism with type 2 diabetes...
  36. doi request reprint What controls the timing of puberty? An update on progress from genetic investigation
    Zofia Kz Gajdos
    Division of Endocrinology, Children s Hospital, Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA
    Curr Opin Endocrinol Diabetes Obes 16:16-24. 2009
    ..However, although genetic variation is known to influence the normal spectrum of pubertal timing, the specific genes involved remain unknown...
  37. ncbi request reprint Demonstrating stratification in a European American population
    Catarina D Campbell
    Program in Genomics and Division of Endocrinology, Children s Hospital, 300 Longwood Avenue, Boston, Massachusetts 02115, USA
    Nat Genet 37:868-72. 2005
    ..The failure of standard methods to detect this stratification indicates that new methods may be required...
  38. ncbi request reprint Genetic model testing and statistical power in population-based association studies of quantitative traits
    Guillaume Lettre
    Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA
    Genet Epidemiol 31:358-62. 2007
    ..Our observations were confirmed by analyzing an existing genetic association dataset in which we detect the effect of a KCNJ11 variant on insulinogenic index in unrelated non-diabetic individuals...
  39. pmc SCRIB and PUF60 are primary drivers of the multisystemic phenotypes of the 8q24.3 copy-number variant
    Andrew Dauber
    Division of Endocrinology, Boston Children s Hospital, Boston, MA 02115, USA Program in Medical and Population Genetics, Broad Institute, Cambridge, MA 02115, USA
    Am J Hum Genet 93:798-811. 2013
    ....
  40. pmc Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index
    Elizabeth K Speliotes
    Metabolism Initiative and Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, USA
    Nat Genet 42:937-48. 2010
    ..Furthermore, genes in other newly associated loci may provide new insights into human body weight regulation...
  41. pmc Lin28a transgenic mice manifest size and puberty phenotypes identified in human genetic association studies
    Hao Zhu
    Stem Cell Transplantation Program, Division of Pediatric Hematology Oncology, Children s Hospital Boston and Dana Farber Cancer Institute, Department of Pathology, Harvard Medical School, Boston, Massachusetts, USA
    Nat Genet 42:626-30. 2010
    ..Here we report a mouse that models the human phenotypes associated with genetic variation in the Lin28-Let-7 pathway...
  42. pmc Replication and fine mapping of asthma-associated loci in individuals of African ancestry
    David B Kantor
    Division of Critical Care Medicine, Department of Anesthesiology, Perioperative and Pain Medicine, Boston Children s Hospital, 300 Longwood Avenue, Boston, MA, 02115, USA
    Hum Genet 132:1039-47. 2013
    ..These results improve the understanding of asthma genetics and further demonstrate the utility of genetic studies in populations other than those of largely European ancestry. ..
  43. ncbi request reprint Meta-analysis of genetic association studies supports a contribution of common variants to susceptibility to common disease
    Kirk E Lohmueller
    Whitehead Massachuetts Institute of Technology Center for Genome Research, Cambridge, Massachusetts 02139, USA
    Nat Genet 33:177-82. 2003
    ..We conclude that there are probably many common variants in the human genome with modest but real effects on common disease risk, and that studies using large samples will convincingly identify such variants...
  44. pmc DNA polymorphisms at the BCL11A, HBS1L-MYB, and beta-globin loci associate with fetal hemoglobin levels and pain crises in sickle cell disease
    Guillaume Lettre
    Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
    Proc Natl Acad Sci U S A 105:11869-74. 2008
    ..We also have shown that HbF-associated SNPs associate with pain crisis rate in SCD patients. These results provide a clear example of inherited common sequence variants modifying the severity of a monogenic disease...
  45. ncbi request reprint Determination of sequence variation and haplotype structure for the gonadotropin-releasing hormone (GnRH) and GnRH receptor genes: investigation of role in pubertal timing
    Ines L Sedlmeyer
    Division of Endocrinology and Genetics, Department of Medicine, Children s Hospital, Hravard Medical School, Boston, MA 02115, USA
    J Clin Endocrinol Metab 90:1091-9. 2005
    ..We conclude that genetic variation in GNRH1 and GNRHR is not likely to be a substantial modulator of pubertal timing in the general population...
  46. pmc A survey of allelic imbalance in F1 mice
    Catarina D Campbell
    Program in Genomics and Division of Endocrinology, Children s Hospital, Boston, Massachusetts 02115, USA
    Genome Res 18:555-63. 2008
    ..Finally, we observed that the presence of AI in human genes was correlated to the presence of AI in the mouse orthologs (one-tailed P = 0.003), suggesting that certain genes may be more tolerant of cis-acting variation across species...
  47. pmc Genetic signatures of strong recent positive selection at the lactase gene
    Todd Bersaglieri
    Divisions of Genetics and Endocrinology, Harvard Medical School, Boston, MA 02115, USA
    Am J Hum Genet 74:1111-20. 2004
    ....
  48. pmc Improved ancestry inference using weights from external reference panels
    Chia Yen Chen
    Department of Epidemiology, Department of Biostatistics, Harvard School of Public Health, Boston, MA 02115, USA
    Bioinformatics 29:1399-406. 2013
    ....
  49. pmc Common body mass index-associated variants confer risk of extreme obesity
    Chris Cotsapas
    Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA 02114, USA
    Hum Mol Genet 18:3502-7. 2009
    ..Our results suggest that variants influencing BMI also contribute to severe obesity, a condition at the extreme of the phenotypic spectrum rather than a distinct condition...
  50. doi request reprint Modifier genes in Mendelian disorders: the example of hemoglobin disorders
    Vijay G Sankaran
    Division of Hematology Oncology, Children s Hospital Boston, Boston, Massachusetts, USA
    Ann N Y Acad Sci 1214:47-56. 2010
    ..We finally go on to discuss future avenues of research that may allow us to gain further insight into the poorly understood clinical heterogeneity of this fascinating set of common genetic diseases...
  51. pmc Genome-wide association of early-onset myocardial infarction with single nucleotide polymorphisms and copy number variants
    Sekar Kathiresan
    Cardiovascular Research Center and Cardiology Division, Massachusetts General Hospital, Boston, Massachusetts 02114, USA
    Nat Genet 41:334-41. 2009
    ..SNPs at nine loci were reproducibly associated with myocardial infarction, but tests of common and rare CNVs failed to identify additional associations with myocardial infarction risk...
  52. pmc A novel deletion of IGF1 in a patient with idiopathic short stature provides insight Into IGF1 haploinsufficiency
    Lara Batey
    Division of Endocrinology L B, J E M, J N H, A D, Boston Children s Hospital, Boston, Massachusetts 02115 Shanghai Children s Medical Center Y Y, Shanghai Jiaotong University School of Medicine, Shanghai 200127, China Pediatrics Institute B W, Key Laboratory of Neonatal Diseases, Ministry of Health, Children s Hospital of Fudan University, Shanghai 201102, PR China Program in Medical and Population Genetics J N H, Broad Institute, Cambridge, Massachusetts 02142 Department of Genetics J N H, Harvard Medical School, Boston, Massachusetts 02115 Department of Pathology Y S, Harvard Medical School, and Department of Laboratory Medicine, Boston Children s Hospital, Boston, Massachusetts 02115 and Shanghai Children s Medical Center Y S, Shanghai Jiaotong University School of Medicine, Shanghai 200127, China
    J Clin Endocrinol Metab 99:E153-9. 2014
    ..Frequently, the underlying etiology of short stature is unknown, resulting in a diagnosis of idiopathic short stature. Rare genetic defects in the GH/IGF-1 axis have been found to cause short stature...
  53. pmc Loss of function of the melanocortin 2 receptor accessory protein 2 is associated with mammalian obesity
    Masato Asai
    Division of Endocrinology, Department of Medicine, Boston Children s Hospital, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA
    Science 341:275-8. 2013
    ..In a study of humans with severe, early-onset obesity, we found four rare, potentially pathogenic genetic variants in MRAP2, suggesting that the gene may also contribute to body weight regulation in humans. ..
  54. pmc Large-scale pooled next-generation sequencing of 1077 genes to identify genetic causes of short stature
    Sophie R Wang
    Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Clin Endocrinol Metab 98:E1428-37. 2013
    ..The majority of patients presenting with short stature do not receive a definitive diagnosis. Advances in genetic sequencing allow for large-scale screening of candidate genes, potentially leading to genetic diagnoses...
  55. ncbi request reprint Haplotype structure and genotype-phenotype correlations of the sulfonylurea receptor and the islet ATP-sensitive potassium channel gene region
    Jose C Florez
    Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA
    Diabetes 53:1360-8. 2004
    ....
  56. pmc Genetic defect in CYP24A1, the vitamin D 24-hydroxylase gene, in a patient with severe infantile hypercalcemia
    Andrew Dauber
    Division of Endocrinology, Children s Hospital Boston, Clinical Investigator Training Program, Boston, Massachusetts 02115, USA
    J Clin Endocrinol Metab 97:E268-74. 2012
    ..Idiopathic infantile hypercalcemia (IIH) is a disorder the genetic etiology and physiological basis of which are not well understood...
  57. pmc Genetic determinants of pubertal timing in the general population
    Zofia K Z Gajdos
    Program in Genomics and Division of Endocrinology, Children s Hospital, Boston, MA 02115, United States
    Mol Cell Endocrinol 324:21-9. 2010
    ....
  58. pmc Fatty liver is associated with dyslipidemia and dysglycemia independent of visceral fat: the Framingham Heart Study
    Elizabeth K Speliotes
    Department of Gastroenterology, Massachusetts General Hospital, Boston, MA 02114, USA
    Hepatology 51:1979-87. 2010
    ..001), whereas associations with SBP and DBP were attenuated (P > 0.05)...
  59. doi request reprint Progress in genome-wide association studies of human height
    Joel N Hirschhorn
    Divisions of Endocrinology and Genetics and Program in Genomics, Children s Hospital, Boston, MA 2115 USA
    Horm Res 71:5-13. 2009
    ....
  60. pmc MEF2A sequence variants and coronary artery disease: a change of heart?
    David Altshuler
    Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA
    J Clin Invest 115:831-3. 2005
    ..These results do not support the hypothesis that mutations in MEF2A are a cause of CAD and/or MI but do illustrate general principles regarding the difficulty of connecting genetic variation to common diseases...
  61. ncbi request reprint Genetic association studies of complex traits: design and analysis issues
    Christopher Newton-Cheh
    Broad Institute of Harvard and MIT, One Kendall Square, Building 300, Cambridge, MA 02139, USA
    Mutat Res 573:54-69. 2005
    ..Heritable and accurately measured phenotypes, carefully matched large samples, well-chosen genetic markers, and adequate standards in genotyping, analysis, and interpretation are all integral parts of a high-quality association study...
  62. doi request reprint Genome-wide association studies: results from the first few years and potential implications for clinical medicine
    Joel N Hirschhorn
    Department of Genetics, Harvard Medical School, Program in Genomics and Division of Genetics, Children s Hospital, Boston, Massachusetts 02115, USA
    Annu Rev Med 62:11-24. 2011
    ..The greatest impact of GWA studies may not be in predictive medicine but rather in the development over the next decades of therapies based on novel biological insights...
  63. pmc Ultraconserved elements: analyses of dosage sensitivity, motifs and boundaries
    Charleston W K Chiang
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Genetics 180:2277-93. 2008
    ....
  64. pmc Burden of rare sarcomere gene variants in the Framingham and Jackson Heart Study cohorts
    Alexander G Bick
    Department of Genetics, Harvard Medical School, Boston, MA 02115, USA
    Am J Hum Genet 91:513-9. 2012
    ..3) in the FHS cohort, suggesting that cardiovascular risk assessment in the general population can benefit from rare variant analysis...
  65. pmc Whole exome sequencing reveals a novel mutation in CUL7 in a patient with an undiagnosed growth disorder
    Andrew Dauber
    Division of Endocrinology, Children s Hospital Boston, Boston, MA, 02115, USA
    J Pediatr 162:202-4.e1. 2013
    ..Whole exome sequencing demonstrated a novel homozygous frameshift mutation in CUL7, one of the causative genes of 3-M syndrome. We discuss the utility of exome sequencing in diagnosing rare disorders...
  66. pmc Association testing of previously reported variants in a large case-control meta-analysis of diabetic nephropathy
    Winfred W Williams
    Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, USA
    Diabetes 61:2187-94. 2012
    ..In conclusion, we were unable to replicate most of the previously reported genetic associations for DN, and significance for the EPO promoter association was attenuated...
  67. pmc Genome-wide association of copy-number variation reveals an association between short stature and the presence of low-frequency genomic deletions
    Andrew Dauber
    Division of Endocrinology, Children s Hospital Boston, Boston, MA 02115, USA
    Am J Hum Genet 89:751-9. 2011
    ..Additionally, copy-number variation might contribute to genetic variation in stature in the general population...
  68. ncbi request reprint Lactose and lactase--who is lactose intolerant and why?
    Robert K Montgomery
    Division of Genetics, Department of Medicine, Program in Genomics, Children s Hospital, Boston, MA 02115, USA
    J Pediatr Gastroenterol Nutr 45:S131-7. 2007
    ..Any hypothesis for the control of lactase expression must reconcile the presence of high levels of activity in early life in all humans and the characteristic loss of activity found subsequently in many but not all people...
  69. ncbi request reprint PGC-1alpha-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes
    Vamsi K Mootha
    Whitehead Institute MIT Center for Genome Research, Cambridge, Massachusetts, USA
    Nat Genet 34:267-73. 2003
    ..Our results associate this gene set with clinically important variation in human metabolism and illustrate the value of pathway relationships in the analysis of genomic profiling experiments...
  70. doi request reprint Genome-wide association studies in pediatric endocrinology
    Andrew Dauber
    Division of Endocrinology, Children s Hospital Boston, Boston, MA 02115, USA
    Horm Res Paediatr 75:322-8. 2011
    ..We then discuss the present and future implications of these findings with regards to disease prediction, uncovering basic biology, and the development of novel therapeutic agents...
  71. ncbi request reprint Conserved noncoding sequences are selectively constrained and not mutation cold spots
    Jared A Drake
    Program in Genomics and Division of Endocrinology, Children s Hospital, Boston, Massachusetts 02115, USA
    Nat Genet 38:223-7. 2006
    ..Thus, conserved noncoding variants are more likely to be functional. Allele frequency distributions highlight selectively constrained genomic regions that should be intensively surveyed for functionally important variation...
  72. ncbi request reprint Assessing the impact of population stratification on genetic association studies
    Matthew L Freedman
    Department of Medicine and Molecular Biology, Massachusetts General Hospital, Boston, and Program in Medical and Population Genetics, Broad Institute, Cambridge, USA
    Nat Genet 36:388-93. 2004
    ..Our results suggest that modest amounts of stratification can exist even in well designed studies...
  73. ncbi request reprint Genetic and genomic approaches to studying stature and pubertal timing
    Joel N Hirschhorn
    Children s Hospital Harvard Medical School, Boston, MA 02115, USA
    Pediatr Endocrinol Rev 2:351-4. 2005
    ..For both association and linkage studies to be successful, large samples and careful interpretation are critical...
  74. pmc The history of African gene flow into Southern Europeans, Levantines, and Jews
    Priya Moorjani
    Department of Genetics, Harvard Medical School, Boston, Massachusetts, United States of America
    PLoS Genet 7:e1001373. 2011
    ..For the Jewish admixture, we obtain an average estimated date of about 72 generations. This may reflect descent of these groups from a common ancestral population that already had some African ancestry prior to the Jewish Diasporas...
  75. doi request reprint Delayed puberty due to a novel mutation in CHD7 causing CHARGE syndrome
    Andrew Dauber
    Division of Endocrinology, CLS 16, Children s Hospital Boston, 300 Longwood Ave, Boston, MA 02115, USA
    Pediatrics 126:e1594-8. 2010
    ..Finally, we illustrate that Bayes' theorem is a useful statistical tool for interpreting novel missense mutations of unknown significance...
  76. pmc Gencrypt: one-way cryptographic hashes to detect overlapping individuals across samples
    Michael C Turchin
    Children s Hospital Boston, Boston, MA 02115, USA
    Bioinformatics 28:886-8. 2012
    ..To resolve this problem, we created a software tool, Gencrypt, which utilizes a security protocol known as one-way cryptographic hashes to allow overlapping participants to be identified without sharing individual-level data...
  77. pmc Evidence of widespread selection on standing variation in Europe at height-associated SNPs
    Michael C Turchin
    Division of Genetics, Children s Hospital Boston, Massachusetts, USA
    Nat Genet 44:1015-9. 2012
    ..The systematic frequency differences are consistent with the presence of widespread weak selection (selection coefficients ∼10(-3)-10(-5) per allele) rather than genetic drift alone (P < 10(-15))...
  78. ncbi request reprint Detection of regulatory variation in mouse genes
    Christopher R Cowles
    Whitehead Institute and MIT Center for Genome Research, Nine Cambridge Center, Cambridge, Massachusetts 02142, USA
    Nat Genet 32:432-7. 2002
    ..The results indicate that larger-scale surveys in both mouse and human could identify a substantial number of genes with common regulatory variation...
  79. ncbi request reprint A comprehensive review of genetic association studies
    Joel N Hirschhorn
    Whitehead Institute MIT Center for Genome Research, Cambridge, MA 02139, USA
    Genet Med 4:45-61. 2002
    ..In particular, we emphasize the need for caution in drawing conclusions from a single report of an association between a genetic variant and disease susceptibility...
  80. ncbi request reprint Genetic epidemiology of type 1 diabetes
    Joel N Hirschhorn
    Divisions of Genetics and Endocrinology, Children s Hospital, Department of Genetics, Harvard Medical School, Boston, MA, USA
    Pediatr Diabetes 4:87-100. 2003
    ..Prospects for the future of type 1 diabetes genetics research are considered...
  81. ncbi request reprint Pedigree analysis of constitutional delay of growth and maturation: determination of familial aggregation and inheritance patterns
    Ines L Sedlmeyer
    Department of Medicine, Children s Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA
    J Clin Endocrinol Metab 87:5581-6. 2002
    ..The future identification of these major and modifying genes is an exciting prospect that would improve our understanding of the factors that regulate human pubertal timing and modulate the human reproductive endocrine axis...
  82. ncbi request reprint Genetics of common forms of obesity: a brief overview
    Helen N Lyon
    Children s Hospital Boston, Boston, MA 02115, USA
    Am J Clin Nutr 82:215S-217S. 2005
    ..New research tools and large studies will lead to an understanding of genes and their interaction to cause obesity, which may help guide successful interventions and treatments...
  83. ncbi request reprint Single-gene mutations and increased left ventricular wall thickness in the community: the Framingham Heart Study
    Hiroyuki Morita
    The Program in Genomics Applications CardioGenomics Group Department of Genetics, NRB Room 256, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA
    Circulation 113:2697-705. 2006
    ....
  84. pmc A comprehensive analysis of common genetic variation in prolactin (PRL) and PRL receptor (PRLR) genes in relation to plasma prolactin levels and breast cancer risk: the multiethnic cohort
    Sulggi A Lee
    Department of Preventive Medicine, University of Southern California Keck School of Medicine, Norris Comprehensive Cancer Center, Los Angeles, CA, USA
    BMC Med Genet 8:72. 2007
    ..Prospective epidemiological studies have also shown that women with higher circulating PRL levels have an increase in risk of breast cancer, suggesting that variability in PRL may also be important in determining a woman's risk...
  85. ncbi request reprint CCL2 polymorphisms are associated with serum monocyte chemoattractant protein-1 levels and myocardial infarction in the Framingham Heart Study
    David H McDermott
    National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892 1886, USA
    Circulation 112:1113-20. 2005
    ..Monocyte chemoattractant protein-1 (MCP-1) is a chemokine strongly implicated in promoting atherosclerosis in animal models, but human genetic evidence is contradictory...
  86. ncbi request reprint Clarifying the PROGINS allele association in ovarian and breast cancer risk: a haplotype-based analysis
    Celeste Leigh Pearce
    Department of Preventive Medicine, Norris Comprehensive Cancer Center, University of Southern California, Keck School of Medicine, Los Angeles, CA 90089, USA
    J Natl Cancer Inst 97:51-9. 2005
    ..We set out to refine the association between common variation at the PGR gene locus and these two diseases...
  87. ncbi request reprint Phenotypic variation in constitutional delay of growth and puberty: relationship to specific leptin and leptin receptor gene polymorphisms
    Indraneel Banerjee
    Department of Paediatric Endocrinology, Royal Manchester Children s Hospital, UK
    Eur J Endocrinol 155:121-6. 2006
    ..This study has assessed whether a) L or LR gene polymorphisms were associated with CDGP and b) the CDGP phenotype was influenced by these polymorphisms...
  88. ncbi request reprint Association testing of the protein tyrosine phosphatase 1B gene (PTPN1) with type 2 diabetes in 7,883 people
    Jose C Florez
    Department of Endocrinology, University Hospital MAS, Lund University, Malmo, Sweden
    Diabetes 54:1884-91. 2005
    ....
  89. pmc Common variants near MC4R are associated with fat mass, weight and risk of obesity
    Ruth J F Loos
    MRC Epidemiology Unit, Addenbrooke s Hospital, Cambridge CB2 0QQ, UK
    Nat Genet 40:768-75. 2008
    ....
  90. pmc Phenotype-genotype association grid: a convenient method for summarizing multiple association analyses
    Daniel Levy
    National Heart, Lung, and Blood Institute, Bethesda, MD, USA
    BMC Genet 7:30. 2006
    ..Hundreds of statistical tests may be performed for a single SNP, thereby complicating interpretation of results and inhibiting identification of patterns of association...
  91. ncbi request reprint A common genetic variant in the NOS1 regulator NOS1AP modulates cardiac repolarization
    Dan E Arking
    McKusick Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
    Nat Genet 38:644-51. 2006
    ..Approximately 60% of subjects of European ancestry carry at least one minor allele of the NOS1AP genetic variant, which explains up to 1.5% of QT interval variation...
  92. ncbi request reprint Common genetic variation in five thrombosis genes and relations to plasma hemostatic protein level and cardiovascular disease risk
    Sekar Kathiresan
    National Heart, Lung, and Blood Institute Framingham Heart Study, Framingham, MA 01702 5827, USA
    Arterioscler Thromb Vasc Biol 26:1405-12. 2006
    ..We undertook a linkage disequilibrium (LD)-based genetic approach to investigate the hypothesis that common sequence variants in 5 thrombosis genes influence plasma hemostatic protein levels or risk of cardiovascular disease (CVD)...
  93. ncbi request reprint 5' flanking variants of resistin are associated with obesity
    James C Engert
    Montreal Genome Centre, McGill University Health Centre Research Institute, Montreal, Canada
    Diabetes 51:1629-34. 2002
    ..In contrast, in case/control and family-based study populations from Scandinavia, we saw no effect on BMI with either of these promoter variants. No association was seen with diabetes in any of the population samples...
  94. ncbi request reprint Contribution of clinical correlates and 13 C-reactive protein gene polymorphisms to interindividual variability in serum C-reactive protein level
    Sekar Kathiresan
    Framingham Heart Study, Framingham, MA 01702 5827, USA
    Circulation 113:1415-23. 2006
    ..Serum C-reactive protein (CRP) level is a heritable complex trait that predicts incident cardiovascular disease. We investigated the clinical and genetic sources of interindividual variability in serum CRP...
  95. pmc Genetic variation in the HSD17B1 gene and risk of prostate cancer
    Peter Kraft
    Program in Molecular and Genetic Epidemiology, Harvard School of Public Health, Boston, Massachusetts, United States of America
    PLoS Genet 1:e68. 2005
    ..These results suggest that the germline variants in HSD17B1 characterized by these htSNPs do not substantially influence the risk of prostate cancer in U.S. and European whites...
  96. ncbi request reprint Comprehensive survey of common genetic variation at the plasminogen activator inhibitor-1 locus and relations to circulating plasminogen activator inhibitor-1 levels
    Sekar Kathiresan
    National Heart, Lung, and Blood Institute s Framingham Heart Study, Framingham, Massachusetts 01702 5827, USA
    Circulation 112:1728-35. 2005
    ....
  97. ncbi request reprint Genetic variation at the CYP19A1 locus predicts circulating estrogen levels but not breast cancer risk in postmenopausal women
    Christopher A Haiman
    Department of Preventive Medicine, Keck School of Medicine, University of Southern California, 1441 Eastlake Avenue, Los Angeles, CA 90033, USA
    Cancer Res 67:1893-7. 2007
    ..Thus, although genetic variation in CYP19A1 produces measurable differences in estrogen levels among postmenopausal women, the magnitude of the change was insufficient to contribute detectably to breast cancer...
  98. ncbi request reprint Common genetic variation at the endothelial nitric oxide synthase locus and relations to brachial artery vasodilator function in the community
    Sekar Kathiresan
    Framingham Heart Study, National Heart, Lung, and Blood Institute, Framingham, MA, USA
    Circulation 112:1419-27. 2005
    ..Sequence variants at the endothelial nitric oxide synthase (NOS3) locus have been associated with endothelial function measures, but replication has been limited...
  99. doi request reprint Genome-wide association studies for complex traits: consensus, uncertainty and challenges
    Mark I McCarthy
    Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK
    Nat Rev Genet 9:356-69. 2008
    ....
  100. ncbi request reprint Modeling and E-M estimation of haplotype-specific relative risks from genotype data for a case-control study of unrelated individuals
    Daniel O Stram
    Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA
    Hum Hered 55:179-90. 2003
    ..1]) the differences between the three methods are very small and in particular that the single imputation method may be expected to work extremely well...
  101. pmc Genome-wide association study shows BCL11A associated with persistent fetal hemoglobin and amelioration of the phenotype of beta-thalassemia
    Manuela Uda
    Istituto di Neurogenetica e Neurofarmacologia, Consiglio Nazionale delle Ricerche, Cittadella Universitaria di Monserrato, Monserrato, Cagliari, Italy
    Proc Natl Acad Sci U S A 105:1620-5. 2008
    ..We expect our findings will help to characterize the molecular mechanisms of fetal globin regulation and could eventually contribute to the development of new therapeutic approaches for beta-thalassemia and sickle cell anemia...