Research Topics
Genomes and Genes
| Joel N HirschhornSummaryAffiliation: Harvard University Country: USA Publications
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Detail Information
Publications
Genome-wide association studies for common diseases and complex traitsJoel 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...- Genetic approaches to studying common diseases and complex traitsJoel 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... - Association of common variation in the HNF1alpha gene region with risk of type 2 diabetesWendy Winckler
Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA
Diabetes 54:2336-42. 2005.... - Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levelsRicha 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... - Transferability of tag SNPs in genetic association studies in multiple populationsPaul 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... - The Krüppel-like factor 11 (KLF11) Q62R polymorphism is not associated with type 2 diabetes in 8,676 peopleJose 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... - Association testing of variants in the hepatocyte nuclear factor 4alpha gene with risk of type 2 diabetes in 7,883 peopleWendy Winckler
Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA
Diabetes 54:886-92. 2005.... - Common variants in the ENPP1 gene are not reproducibly associated with diabetes or obesityHelen 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... - 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 menCatarina 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... 
Association studies of common variants in 10 hypogonadotropic hypogonadism genes with age at menarcheZofia 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)...- A common genetic variant is associated with adult and childhood obesityAlan 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... - PNPLA3 variants specifically confer increased risk for histologic nonalcoholic fatty liver disease but not metabolic diseaseElizabeth K Speliotes
Department of Gastroenterology, Massachusetts General Hospital, Boston, MA 02114, USA
Hepatology 52:904-12. 2010..CONCLUSION: Genetic variation at PNPLA3 confers a markedly increased risk of increasingly severe histological features of NAFLD, without a strong effect on metabolic syndrome component traits... - Common single nucleotide polymorphisms in TCF7L2 are reproducibly associated with type 2 diabetes and reduce the insulin response to glucose in nondiabetic individualsRicha 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... - The ENPP1 K121Q polymorphism is associated with type 2 diabetes in European populations: evidence from an updated meta-analysis in 42,042 subjectsJarred 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... - Candidate gene association resource (CARe): design, methods, and proof of conceptKiran 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... 
Human fetal hemoglobin expression is regulated by the developmental stage-specific repressor BCL11AVijay 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...- Use of weighted reference panels based on empirical estimates of ancestry for capturing untyped variationMatthew R L Egyud
Children s Hospital, Boston, MA 02115, USA
Hum Genet 125:295-303. 2009.... - High-density haplotype structure and association testing of the insulin-degrading enzyme (IDE) gene with type 2 diabetes in 4,206 peopleJose 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... - Evaluation of common variants in the six known maturity-onset diabetes of the young (MODY) genes for association with type 2 diabetesWendy 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... - Ultraconserved elements in the human genome: association and transmission analyses of highly constrained single-nucleotide polymorphismsCharleston 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... - Comprehensive association testing of common mitochondrial DNA variation in metabolic diseaseRicha 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... - Common genetic variation in eight genes of the GH/IGF1 axis does not contribute to adult height variationGuillaume 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.... - Enhanced statistical tests for GWAS in admixed populations: assessment using African Americans from CARe and a Breast Cancer ConsortiumBogdan 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... - Systematic evaluation of genetic variation at the androgen receptor locus and risk of prostate cancer in a multiethnic cohort studyMatthew 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... - Common variation in BRCA2 and breast cancer risk: a haplotype-based analysis in the Multiethnic CohortMatthew 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... - Haplotype structures and large-scale association testing of the 5' AMP-activated protein kinase genes PRKAA2, PRKAB1, and PRKAB2 [corrected] with type 2 diabetesMaria 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... - Association of common variants in NPPA and NPPB with circulating natriuretic peptides and blood pressureChristopher 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... 
The association of a SNP upstream of INSIG2 with body mass index is reproduced in several but not all cohortsHelen N Lyon
Program in Genomics, Divisions of Genetics and Endocrinology, Children s Hospital, Boston, Massachusetts, USA
PLoS Genet 3:e61. 2007....- The efficacy of detecting variants with small effects on the Affymetrix 6.0 platform using pooled DNACharleston 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... - Genetic model testing and statistical power in population-based association studies of quantitative traitsGuillaume 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... - Lin28a transgenic mice manifest size and puberty phenotypes identified in human genetic association studiesHao 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... - Association testing in 9,000 people fails to confirm the association of the insulin receptor substrate-1 G972R polymorphism with type 2 diabetesJose 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... - Association analyses of 249,796 individuals reveal 18 new loci associated with body mass indexElizabeth 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... - Demonstrating stratification in a European American populationCatarina 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... - Identification of ten loci associated with height highlights new biological pathways in human growthGuillaume 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... - What controls the timing of puberty? An update on progress from genetic investigationZofia 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... - A survey of allelic imbalance in F1 miceCatarina 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... - Meta-analysis of genetic association studies supports a contribution of common variants to susceptibility to common diseaseKirk 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... - DNA polymorphisms at the BCL11A, HBS1L-MYB, and beta-globin loci associate with fetal hemoglobin levels and pain crises in sickle cell diseaseGuillaume 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... - Determination of sequence variation and haplotype structure for the gonadotropin-releasing hormone (GnRH) and GnRH receptor genes: investigation of role in pubertal timingInes 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... - Haplotype structure and genotype-phenotype correlations of the sulfonylurea receptor and the islet ATP-sensitive potassium channel gene regionJose C Florez
Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA
Diabetes 53:1360-8. 2004.... - Modifier genes in Mendelian disorders: the example of hemoglobin disordersVijay 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... - Common body mass index-associated variants confer risk of extreme obesityChris 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... - Genome-wide association of early-onset myocardial infarction with single nucleotide polymorphisms and copy number variantsSekar 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... - Genetic defect in CYP24A1, the vitamin D 24-hydroxylase gene, in a patient with severe infantile hypercalcemiaAndrew 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... - Ultraconserved elements: analyses of dosage sensitivity, motifs and boundariesCharleston W K Chiang
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA
Genetics 180:2277-93. 2008.... - Genetic determinants of pubertal timing in the general populationZofia 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.... - Genome-wide association studies: results from the first few years and potential implications for clinical medicineJoel 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... - Progress in genome-wide association studies of human heightJoel N Hirschhorn
Divisions of Endocrinology and Genetics and Program in Genomics, Children s Hospital, Boston, MA 2115 USA
Horm Res 71:5-13. 2009.... - 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... - Fatty liver is associated with dyslipidemia and dysglycemia independent of visceral fat: the Framingham Heart StudyElizabeth K Speliotes
Department of Gastroenterology, Massachusetts General Hospital, Boston, MA 02114, USA
Hepatology 51:1979-87. 2010..This work begins to dissect the specific links between fat depots and metabolic disease... - Genetic signatures of strong recent positive selection at the lactase geneTodd Bersaglieri
Divisions of Genetics and Endocrinology, Harvard Medical School, Boston, MA 02115, USA
Am J Hum Genet 74:1111-20. 2004.... - Genetic association studies of complex traits: design and analysis issuesChristopher 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... - Whole exome sequencing reveals a novel mutation in CUL7 in a patient with an undiagnosed growth disorderAndrew 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... - Association testing of previously reported variants in a large case-control meta-analysis of diabetic nephropathyWinfred 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... - Genome-wide association of copy-number variation reveals an association between short stature and the presence of low-frequency genomic deletionsAndrew 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... - Genome-wide association studies in pediatric endocrinologyAndrew 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... - 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... - Conserved noncoding sequences are selectively constrained and not mutation cold spotsJared 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... - Assessing the impact of population stratification on genetic association studiesMatthew 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... - Genetic and genomic approaches to studying stature and pubertal timingJoel 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... - PGC-1alpha-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetesVamsi 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... - The history of African gene flow into Southern Europeans, Levantines, and JewsPriya 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... - Delayed puberty due to a novel mutation in CHD7 causing CHARGE syndromeAndrew 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... - Burden of rare sarcomere gene variants in the Framingham and Jackson Heart Study cohortsAlexander 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... - Gencrypt: one-way cryptographic hashes to detect overlapping individuals across samplesMichael 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... - Evidence of widespread selection on standing variation in Europe at height-associated SNPsMichael 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))... - Detection of regulatory variation in mouse genesChristopher 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... - Genetic epidemiology of type 1 diabetesJoel 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... - A comprehensive review of genetic association studiesJoel 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... - Pedigree analysis of constitutional delay of growth and maturation: determination of familial aggregation and inheritance patternsInes 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... - Genetics of common forms of obesity: a brief overviewHelen 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... - Single-gene mutations and increased left ventricular wall thickness in the community: the Framingham Heart StudyHiroyuki 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.... - A common genetic variant in the NOS1 regulator NOS1AP modulates cardiac repolarizationDan 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... - 5' flanking variants of resistin are associated with obesityJames 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... - Genetic variation in the HSD17B1 gene and risk of prostate cancerPeter 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... - Contribution of clinical correlates and 13 C-reactive protein gene polymorphisms to interindividual variability in serum C-reactive protein levelSekar 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... - Comprehensive survey of common genetic variation at the plasminogen activator inhibitor-1 locus and relations to circulating plasminogen activator inhibitor-1 levelsSekar Kathiresan
National Heart, Lung, and Blood Institute s Framingham Heart Study, Framingham, Massachusetts 01702 5827, USA
Circulation 112:1728-35. 2005.... - Common genetic variation at the endothelial nitric oxide synthase locus and relations to brachial artery vasodilator function in the communitySekar 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... - CCL2 polymorphisms are associated with serum monocyte chemoattractant protein-1 levels and myocardial infarction in the Framingham Heart StudyDavid 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... - Association testing of the protein tyrosine phosphatase 1B gene (PTPN1) with type 2 diabetes in 7,883 peopleJose C Florez
Department of Endocrinology, University Hospital MAS, Lund University, Malmo, Sweden
Diabetes 54:1884-91. 2005.... - Clarifying the PROGINS allele association in ovarian and breast cancer risk: a haplotype-based analysisCeleste 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... - Genetic approaches to stature, pubertal timing, and other complex traitsMark R Palmert
Division of Pediatric Endocrinology and Metabolism, Rainbow Babies and Children's Hospital, University Hospitals of Cleveland, USA
Mol Genet Metab 80:1-10. 2003..Discovery of the genetic variants that regulate these two traits would expand our understanding of human neuroendocrinology, postnatal development, and the general architecture of complex genetic traits... - Modeling and E-M estimation of haplotype-specific relative risks from genotype data for a case-control study of unrelated individualsDaniel 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... - Choosing haplotype-tagging SNPS based on unphased genotype data using a preliminary sample of unrelated subjects with an example from the Multiethnic Cohort StudyDaniel O Stram
Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, Calif 90033, USA
Hum Hered 55:27-36. 2003..A candidate set of htSNPS of a given size is chosen so as to maximize the minimum value of R2h over the common haplotypes, h... - Common genetic variation in five thrombosis genes and relations to plasma hemostatic protein level and cardiovascular disease riskSekar 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)... - Phenotype-genotype association grid: a convenient method for summarizing multiple association analysesDaniel 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... - Genome-wide association studies for complex traits: consensus, uncertainty and challengesMark I McCarthy
Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK
Nat Rev Genet 9:356-69. 2008.... - Common variants near MC4R are associated with fat mass, weight and risk of obesityRuth J F Loos
MRC Epidemiology Unit, Addenbrooke s Hospital, Cambridge CB2 0QQ, UK
Nat Genet 40:768-75. 2008.... - Genome-wide association study shows BCL11A associated with persistent fetal hemoglobin and amelioration of the phenotype of beta-thalassemiaManuela 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... - Common variants in the GDF5-UQCC region are associated with variation in human heightSerena Sanna
Center for Statistical Genetics, Department of Biostatistics, University of Michigan, Ann Arbor, Michigan 48109, USA
Nat Genet 40:198-203. 2008..44 cm (overall P < 10(-15)). Our results indicate that there may be a link between the genetic basis of height and osteoarthritis, potentially mediated through alterations in bone growth and development... - 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 cohortSulggi 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... - A common variant of HMGA2 is associated with adult and childhood height in the general populationMichael N Weedon
Genetics of Complex Traits, Institute of Biomedical and Clinical Science, Peninsula Medical School, Magdalen Road, Exeter EX1 2LU, UK
Nat Genet 39:1245-50. 2007..There are few examples of common genetic variants reproducibly associated with human quantitativetraits; these results represent, to our knowledge, the first consistently replicated association with adult and childhood height... - Replicating genotype-phenotype associationsStephen J Chanock
Division of Cancer Epidemiology and Genetics, Bethesda, Maryland 20892-4605, USA
Nature 447:655-60. 2007 - Vascular stiffness and genetic variation at the endothelial nitric oxide synthase locus: the Framingham Heart studyGary F Mitchell
Cardiovascular Engineering, Inc, Waltham, MA 02453, USA
Hypertension 49:1285-90. 2007..The present study was suggestive of modest relations between common genetic variants at the NOS3 locus and arterial stiffness... - Genetic variation at the CYP19A1 locus predicts circulating estrogen levels but not breast cancer risk in postmenopausal womenChristopher 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... - Phenotypic variation in constitutional delay of growth and puberty: relationship to specific leptin and leptin receptor gene polymorphismsIndraneel 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... - Heritability, linkage, and genetic associations of exercise treadmill test responsesErik Ingelsson
Framingham Study, Framingham, Mass, USA
Circulation 115:2917-24. 2007..The blood pressure (BP) and heart rate responses to exercise treadmill testing predict incidence of cardiovascular disease, but the genetic determinants of hemodynamic and chronotropic responses to exercise are largely unknown... - Investigation of the estrogen receptor-alpha gene with type 2 diabetes and/or nephropathy in African-American and European-American populationsCarla J Gallagher
Center for Human Genomics, Wake Forest University School of Medicine, Medical Center Blvd, Winston Salem, NC 27157, USA
Diabetes 56:675-84. 2007..033) were associated with type 2 diabetes and/or ESRD. Results suggest that intron 1 and intron 2 of the ESR1 gene may contain functionally important regions related to type 2 diabetes or ESRD risk... - Comprehensive evaluation of ESR2 variation and ovarian cancer riskCeleste Leigh Pearce
USC Norris Comprehensive Cancer Center and Department of Preventive Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, CA 90089, USA
Cancer Epidemiol Biomarkers Prev 17:393-6. 2008..28-11.73; P = 0.016). Haplotype D was also reported by the BPC3 to be associated with increased risk of breast cancer. This haplotype warrants further investigation to rule out any effect with invasive ovarian cancer risk... - Liver fat is reproducibly measured using computed tomography in the Framingham Heart StudyElizabeth K Speliotes
Departments of Gastroenterology, Massachusettes General Hospital, Massachusetts, USA
J Gastroenterol Hepatol 23:894-9. 2008..We sought to determine the feasibility of and optimal protocol for quantifying fat content in the liver in the Framingham Heart Study using multidetector computed tomography (MDCT) scanning...