David Altshuler

Summary

Affiliation: Harvard University
Country: USA

Publications

  1. pmc The functional spectrum of low-frequency coding variation
    Gabor T Marth
    Department of Biology, Boston College, 140 Commonwealth Avenue, Chestnut Hill, MA 02467, USA
    Genome Biol 12:R84. 2011
  2. 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
  3. pmc Integrating common and rare genetic variation in diverse human populations
    David M Altshuler
    Broad Institute, 7 Cambridge Center, Cambridge, Massachusetts 02138, USA
    Nature 467:52-8. 2010
  4. pmc Genetic mapping in human disease
    David Altshuler
    Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA
    Science 322:881-8. 2008
  5. ncbi request reprint Genetics. Harvesting medical information from the human family tree
    David Altshuler
    Broad Institute of Harvard and Massachusetts Institute of Technology, and Massachusetts General Hospital, Boston, MA 02114, USA
    Science 307:1052-3. 2005
  6. pmc Common variants at CD40 and other loci confer risk of rheumatoid arthritis
    Soumya Raychaudhuri
    Program in Medical and Population Genetics, Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA
    Nat Genet 40:1216-23. 2008
  7. 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
  8. 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
  9. pmc Integrated genotype calling and association analysis of SNPs, common copy number polymorphisms and rare CNVs
    Joshua M Korn
    Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA
    Nat Genet 40:1253-60. 2008
  10. pmc Haplotypes of the estrogen receptor beta gene and breast cancer risk
    David G Cox
    Program in Molecular and Genetic Epidemiology, Epidemiology Department, Harvard School of Public Health, Boston, MA, USA
    Int J Cancer 122:387-92. 2008

Research Grants

  1. Human Genome Sequence Variation & the Inherited Basis
    David Altshuler; Fiscal Year: 2004
  2. COMMON VARIATION IN CANDIDATE GENES IN THE DPP
    David Altshuler; Fiscal Year: 2009
  3. A Genome-wide Association Study for Early-Onset Myocardial Infarction
    David Altshuler; Fiscal Year: 2009
  4. A Genome-wide Association Study for Early-Onset Myocardial Infarction
    David Altshuler; Fiscal Year: 2007
  5. Design/Production of Haplotype Map of the Human Genome
    David Altshuler; Fiscal Year: 2005
  6. Genomic variation, hapmap and disease
    David Altshuler; Fiscal Year: 2006
  7. Genome Sequence Variation
    David Altshuler; Fiscal Year: 2006

Detail Information

Publications98

  1. pmc The functional spectrum of low-frequency coding variation
    Gabor T Marth
    Department of Biology, Boston College, 140 Commonwealth Avenue, Chestnut Hill, MA 02467, USA
    Genome Biol 12:R84. 2011
    ....
  2. 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...
  3. pmc Integrating common and rare genetic variation in diverse human populations
    David M Altshuler
    Broad Institute, 7 Cambridge Center, Cambridge, Massachusetts 02138, USA
    Nature 467:52-8. 2010
    ....
  4. pmc Genetic mapping in human disease
    David Altshuler
    Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA
    Science 322:881-8. 2008
    ....
  5. ncbi request reprint Genetics. Harvesting medical information from the human family tree
    David Altshuler
    Broad Institute of Harvard and Massachusetts Institute of Technology, and Massachusetts General Hospital, Boston, MA 02114, USA
    Science 307:1052-3. 2005
  6. pmc Common variants at CD40 and other loci confer risk of rheumatoid arthritis
    Soumya Raychaudhuri
    Program in Medical and Population Genetics, Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA
    Nat Genet 40:1216-23. 2008
    ..1 x 10(-7) overall), CDK6 (rs42041, P = 0.010 replication, P = 4.0 x 10(-6) overall), PRKCQ (rs4750316, P = 0.0078 replication, P = 4.4 x 10(-6) overall), and KIF5A-PIP4K2C (rs1678542, P = 0.0026 replication, P = 8.8 x 10(-8) overall)...
  7. 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...
  8. 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
    ....
  9. pmc Integrated genotype calling and association analysis of SNPs, common copy number polymorphisms and rare CNVs
    Joshua M Korn
    Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA
    Nat Genet 40:1253-60. 2008
    ..The Birdsuite software is applied here to data from the Affymetrix SNP 6.0 array. Additionally, we describe a method, implemented in PLINK, to utilize these combined SNP and CNV genotypes for association testing with a phenotype...
  10. pmc Haplotypes of the estrogen receptor beta gene and breast cancer risk
    David G Cox
    Program in Molecular and Genetic Epidemiology, Epidemiology Department, Harvard School of Public Health, Boston, MA, USA
    Int J Cancer 122:387-92. 2008
    ..These data suggest that inherited variants in ESR2 (while possibly conferring a small increased risk of breast cancer) are not associated with appreciable (OR > 1.2) changes in breast cancer risk among Caucasian women...
  11. 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...
  12. pmc Extension of type 2 diabetes genome-wide association scan results in the diabetes prevention program
    Allan F Moore
    Center for Human Genetic Research, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA
    Diabetes 57:2503-10. 2008
    ....
  13. 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
    ....
  14. pmc TRAF1-C5 as a risk locus for rheumatoid arthritis--a genomewide study
    Robert M Plenge
    Broad Institute of Harvard and the Massachusetts Institute of Technology, Cambridge, MA, USA
    N Engl J Med 357:1199-209. 2007
    ..We carried out a genomewide association analysis to identify additional genetic loci associated with an increased risk of rheumatoid arthritis...
  15. ncbi request reprint The Kr├╝ppel-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...
  16. 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...
  17. ncbi request reprint A haplotype-based case-control study of BRCA1 and sporadic breast cancer risk
    Matthew L Freedman
    Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA
    Cancer Res 65:7516-22. 2005
    ....
  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. ncbi request reprint Comparison of fine-scale recombination rates in humans and chimpanzees
    Wendy Winckler
    Department of Molecular Biology and Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA 02114 2622, USA
    Science 308:107-11. 2005
    ..Thus, local patterns of recombination rate have evolved rapidly, in a manner disproportionate to the change in DNA sequence...
  20. ncbi request reprint Searching for signals of evolutionary selection in 168 genes related to immune function
    Emily C Walsh
    Novartis Institutes for BioMedical Research, 250 Mass Ave, Cambridge, MA 02139, USA
    Hum Genet 119:92-102. 2006
    ....
  21. ncbi request reprint Detecting recent positive selection in the human genome from haplotype structure
    Pardis C Sabeti
    Whitehead Institute MIT Center for Genome Research, Nine Cambridge Center, Cambridge, Massachusetts 02142, USA
    Nature 419:832-7. 2002
    ..More generally, the method could be used to scan the entire genome for evidence of recent positive selection...
  22. pmc Calibrating a coalescent simulation of human genome sequence variation
    Stephen F Schaffner
    Program in Medical and Population Genetics, The Broad Institute, Cambridge, Massachusetts 02139, USA
    Genome Res 15:1576-83. 2005
    ..We anticipate that this model, for which software is publicly available, and others like it will have numerous applications in empirical studies of human genetics...
  23. ncbi request reprint Efficiency and power in genetic association studies
    Paul I W de Bakker
    Center for Human Genetic Research, Massachusetts General Hospital, 185 Cambridge Street, CPZN 6818, Boston, Massachusetts 02114 2790, USA
    Nat Genet 37:1217-23. 2005
    ..Power is robust to the completeness of the reference panel from which tags are selected. These findings have implications for prioritizing tag SNPs and interpreting association studies...
  24. pmc Admixture mapping identifies 8q24 as a prostate cancer risk locus in African-American men
    Matthew L Freedman
    Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 103:14068-73. 2006
    ..Thus, admixture mapping indicates a major, still-unidentified risk gene for prostate cancer at 8q24, motivating intense work to find it...
  25. pmc Two independent alleles at 6q23 associated with risk of rheumatoid arthritis
    Robert M Plenge
    Program in Medical and Population Genetics, Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA
    Nat Genet 39:1477-82. 2007
    ..We show that these two SNP associations are statistically independent, are each reproducible in the comparison of our data and WTCCC data, and define risk and protective haplotypes for rheumatoid arthritis at 6q23...
  26. pmc Genetic variants near TNFAIP3 on 6q23 are associated with systemic lupus erythematosus
    Robert R Graham
    Program in Medical and Population Genetics, Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA 02142, USA
    Nat Genet 40:1059-61. 2008
    ..These results establish that variants near TNFAIP3 contribute to differential risk of SLE and RA...
  27. 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...
  28. 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...
  29. 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...
  30. ncbi request reprint The structure of haplotype blocks in the human genome
    Stacey B Gabriel
    Whitehead MIT Center for Genome Research, Cambridge, MA 02139, USA
    Science 296:2225-9. 2002
    ..Our results provide a foundation for the construction of a haplotype map of the human genome, facilitating comprehensive genetic association studies of human disease...
  31. pmc Methods for high-density admixture mapping of disease genes
    Nick Patterson
    Program in Medical and Population Genetics, Broad Institute, Cambridge, MA, USA
    Am J Hum Genet 74:979-1000. 2004
    ..A particularly important result is that the power of an admixture mapping study to detect a locus will be nearly the same for a wide range of mixture scenarios: the mixture proportion should be 10%-90% from both ancestral populations...
  32. pmc Genome-wide detection and characterization of positive selection in human populations
    Pardis C Sabeti
    Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02139, USA
    Nature 449:913-8. 2007
    ....
  33. pmc Three functional variants of IFN regulatory factor 5 (IRF5) define risk and protective haplotypes for human lupus
    Robert R Graham
    Program in Medical and Population Genetics, Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA 02142, USA
    Proc Natl Acad Sci U S A 104:6758-63. 2007
    ....
  34. doi request reprint Integrated detection and population-genetic analysis of SNPs and copy number variation
    Steven A McCarroll
    Program in Medical and Population Genetics and Genetic Analysis Platform, The Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA
    Nat Genet 40:1166-74. 2008
    ..Most common, diallelic CNPs were in strong linkage disequilibrium with SNPs, and most low-frequency CNVs segregated on specific SNP haplotypes...
  35. doi request reprint From Darwin's finches to canaries in the coal mine--mining the genome for new biology
    David J Hunter
    Department of Epidemiology, Harvard School of Public Health, Boston, USA
    N Engl J Med 358:2760-3. 2008
  36. ncbi request reprint Sequence variants of estrogen receptor beta and risk of prostate cancer in the National Cancer Institute Breast and Prostate Cancer Cohort Consortium
    Yen Ching Chen
    Channing Laboratory, 181 Longwood Avenue, Boston, MA 02115, USA
    Cancer Epidemiol Biomarkers Prev 16:1973-81. 2007
    ..Estrogen receptor beta (ESR2) may play a role in modulating prostate carcinogenesis through the regulation of genes related to cell proliferation and apoptosis...
  37. pmc A large study of androgen receptor germline variants and their relation to sex hormone levels and prostate cancer risk. Results from the National Cancer Institute Breast and Prostate Cancer Cohort Consortium
    Sara Lindstrom
    Program in Molecular and Genetic Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA
    J Clin Endocrinol Metab 95:E121-7. 2010
    ..A long-standing hypothesis has been that inherited variation in the androgen receptor (AR) gene plays a role in prostate cancer initiation. However, studies to date have been inconclusive and often suffered from small sample sizes...
  38. pmc Genetic variation in GIPR influences the glucose and insulin responses to an oral glucose challenge
    Richa Saxena
    Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Massachusetts, USA
    Nat Genet 42:142-8. 2010
    ..Of the three newly implicated loci (GIPR, ADCY5 and VPS13C), only ADCY5 was found to be associated with type 2 diabetes in collaborating studies (n = 35,869 cases, 89,798 controls, OR = 1.12, 95% CI 1.09-1.15, P = 4.8 x 10(-18))...
  39. pmc Accurately assessing the risk of schizophrenia conferred by rare copy-number variation affecting genes with brain function
    Soumya Raychaudhuri
    Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, United States of America
    PLoS Genet 6:e1001097. 2010
    ..Our method is implemented in the PLINK software package...
  40. pmc Efficiency and power as a function of sequence coverage, SNP array density, and imputation
    Jason Flannick
    Broad Institute of Harvard and MIT, Cambridge, Massachusetts, United States of America
    PLoS Comput Biol 8:e1002604. 2012
    ..Our joint framework informs the use of next-generation sequencing in genome wide association studies and supports development of improved methods for genotype calling...
  41. 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...
  42. 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...
  43. 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...
  44. 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
    ....
  45. doi request reprint 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...
  46. doi request reprint Exome sequencing and directed clinical phenotyping diagnose cholesterol ester storage disease presenting as autosomal recessive hypercholesterolemia
    Nathan O Stitziel
    From the Cardiovascular Division, Department of Medicine N O S and Division of Statistical Genomics N O S, Washington University School of Medicine, Saint Louis, MO Department of Vascular Medicine B S, S S, J J P K, G K H Department of Experimental Vascular Medicine S W F, J C D, and Radiology A J N, Academic Medical Center, Amsterdam, The Netherlands Center for Human Genetic Research, Boston, MA G M P, A M M, D A, S K Program in Medical and Population Genetics, Broad Institute, Cambridge, MA G M P, A M M, D A, S K Fred Hutchinson Cancer Research Center, Seattle, WA P L A, C K Wellcome Trust Centre for Human Genetics A G, M F, H W and Cardiovascular Medicine, Radcliffe Department of Medicine A G, M F, H W, University of Oxford, Oxford, United Kingdom Division of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Department of Medicine
    Arterioscler Thromb Vasc Biol 33:2909-14. 2013
    ..The aim of this study was to identify the molecular pathogenesis of autosomal recessive hypercholesterolemia in this family...
  47. pmc Analysis of case-control association studies with known risk variants
    Noah Zaitlen
    Department of Epidemiology, Department of Biostatistics, Harvard School of Public Health, Boston, MA 02115, USA
    Bioinformatics 28:1729-37. 2012
    ..Roughly, this method estimates model parameters for each known variant while accounting for the published disease prevalence from the epidemiological literature...
  48. pmc Genetic variants at CD28, PRDM1 and CD2/CD58 are associated with rheumatoid arthritis risk
    Soumya Raychaudhuri
    Division of Rheumatology, Immunology, and Allergy, Brigham and Women s Hospital, Boston, Massachusetts, USA
    Nat Genet 41:1313-8. 2009
    ..0008 replication, P = 4 x 10(-6) overall) and FCGR2A (rs12746613, P = 0.0022 replication, P = 2 x 10(-5) overall). Many of these loci are also associated to other immunologic diseases...
  49. pmc Genome coverage and sequence fidelity of phi29 polymerase-based multiple strand displacement whole genome amplification
    J Guillermo Paez
    Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Nucleic Acids Res 32:e71. 2004
    ..These results suggest that phi29MDA yields high fidelity, near-complete genome representation suitable for high resolution genetic analysis...
  50. 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...
  51. ncbi request reprint Human genome sequence variation and the influence of gene history, mutation and recombination
    David E Reich
    Whitehead Institute MIT Center for Genome Research, One Kendall Square, Cambridge, Massachusetts 02139, USA
    Nat Genet 32:135-42. 2002
    ....
  52. ncbi request reprint Common variation in three genes, including a noncoding variant in CFH, strongly influences risk of age-related macular degeneration
    Julian Maller
    Center for Human Genetic Research, Massachusetts General Hospital, 185 Cambridge St, Boston, Massachusetts 02114, USA
    Nat Genet 38:1055-9. 2006
    ..Genotypes at these five common SNPs define a broad spectrum of interindividual disease risk and explain about half of the classical sibling risk of AMD in our study population...
  53. 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...
  54. ncbi request reprint Evaluating and improving power in whole-genome association studies using fixed marker sets
    Itsik Pe'er
    Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts 02114, USA
    Nat Genet 38:663-7. 2006
    ..Finally, we introduce a Bayesian approach to association analysis by weighting the likelihood of each statistical test to reflect the number of putative causal alleles to which it is correlated...
  55. pmc Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis
    Benjamin F Voight
    Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA, USA
    Nat Genet 42:579-89. 2010
    ..We also show that a high proportion of T2D susceptibility loci harbor independent association signals influencing apparently unrelated complex traits...
  56. ncbi request reprint Quality and completeness of SNP databases
    David E Reich
    Program in Medical and Population Genetics, Whitehead Institute MIT Center for Genome Research, One Kendall Square, Cambridge, Massachusetts 02139, USA
    Nat Genet 33:457-8. 2003
    ..Approximately 45% of all human heterozygosity is attributable to SNPs already available from the two databases, and of SNPs with minor-allele frequencies >10%, more than half are represented...
  57. pmc Common variants at 30 loci contribute to polygenic dyslipidemia
    Sekar Kathiresan
    Cardiovascular Research Center and Cardiology Division, Massachusetts General Hospital, Boston, Massachusetts 02114, USA
    Nat Genet 41:56-65. 2009
    ..These results suggest that the cumulative effect of multiple common variants contributes to polygenic dyslipidemia...
  58. 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...
  59. doi request reprint Comparing strategies to fine-map the association of common SNPs at chromosome 9p21 with type 2 diabetes and myocardial infarction
    Jessica Shea
    Program in Medical and Population Genetics, Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Massachusetts, USA
    Nat Genet 43:801-5. 2011
    ..Our association analyses identified more comprehensive sets of variants showing equivalent statistical association with type 2 diabetes or myocardial infarction, but did not identify stronger associations than the original GWAS signals...
  60. pmc A genome-wide linkage and association scan reveals novel loci for autism
    Lauren A Weiss
    Center for Human Genetic Research, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA
    Nature 461:802-8. 2009
    ..The linkage regions reported here provide targets for rare variation screening whereas the discovery of a single novel association demonstrates the action of common variants...
  61. pmc Replication of putative candidate-gene associations with rheumatoid arthritis in >4,000 samples from North America and Sweden: association of susceptibility with PTPN22, CTLA4, and PADI4
    Robert M Plenge
    Broad Institute of MIT and Harvard, Cambridge, MA, USA
    Am J Hum Genet 77:1044-60. 2005
    ....
  62. ncbi request reprint A common haplotype of interferon regulatory factor 5 (IRF5) regulates splicing and expression and is associated with increased risk of systemic lupus erythematosus
    Robert R Graham
    Program in Medical and Population Genetics, Broad Institute of Harvard and the Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA
    Nat Genet 38:550-5. 2006
    ..Thus, a common IRF5 haplotype driving elevated expression of multiple unique isoforms of IRF5 is an important genetic risk factor for SLE, establishing a causal role for type I IFN pathway genes in human autoimmunity...
  63. pmc High-throughput, pooled sequencing identifies mutations in NUBPL and FOXRED1 in human complex I deficiency
    Sarah E Calvo
    Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, USA
    Nat Genet 42:851-8. 2010
    ..Our study illustrates how large-scale sequencing, coupled with functional prediction and experimental validation, can be used to identify causal mutations in individual cases...
  64. pmc Donor-recipient mismatch for common gene deletion polymorphisms in graft-versus-host disease
    Steven A McCarroll
    Department of Molecular Biology, Massachusetts General Hospital, Boston, Massachusetts, USA
    Nat Genet 41:1341-4. 2009
    ..Human genome structural variation merits investigation as a potential mechanism in diseases of alloimmunity...
  65. pmc Erralpha and Gabpa/b specify PGC-1alpha-dependent oxidative phosphorylation gene expression that is altered in diabetic muscle
    Vamsi K Mootha
    The Eli and Edythe L Broad Institute, Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02139 1561, USA
    Proc Natl Acad Sci U S A 101:6570-5. 2004
    ....
  66. pmc The Genome Analysis Toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data
    Aaron McKenna
    Program in Medical and Population Genetics, The Broad Institute of Harvard and MIT, Cambridge, Massachusetts 02142, USA
    Genome Res 20:1297-303. 2010
    ....
  67. 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...
  68. doi request reprint Association between microdeletion and microduplication at 16p11.2 and autism
    Lauren A Weiss
    Autism Consortium, Boston, USA
    N Engl J Med 358:667-75. 2008
    ..Autism spectrum disorder is a heritable developmental disorder in which chromosomal abnormalities are thought to play a role...
  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. pmc Genome-wide association study identifies eight loci associated with blood pressure
    Christopher Newton-Cheh
    Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, USA
    Nat Genet 41:666-76. 2009
    ..These associations between common variants and blood pressure and hypertension offer mechanistic insights into the regulation of blood pressure and may point to novel targets for interventions to prevent cardiovascular disease...
  71. 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...
  72. 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...
  73. pmc Deletion polymorphism upstream of IRGM associated with altered IRGM expression and Crohn's disease
    Steven A McCarroll
    Center for Human Genetic Research, Massachusetts General Hospital, Harvard Medical School, 185 Cambridge Street, Boston, Massachusetts 02114, USA
    Nat Genet 40:1107-12. 2008
    ..These results suggest that the CD association at IRGM arises from an alteration in IRGM regulation that affects the efficacy of autophagy and identify a common deletion polymorphism as a likely causal variant...
  74. ncbi request reprint Evaluating potential for whole-genome studies in Kosrae, an isolated population in Micronesia
    Penelope E Bonnen
    Rockefeller University, 1230 York Avenue, New York, New York 10021, USA
    Nat Genet 38:214-7. 2006
    ..The long-range LD around common alleles and limited diversity result in improved efficiency in genetic studies in this population and augments the power to detect association of 'hidden SNPs'...
  75. ncbi request reprint Choosing haplotype-tagging SNPS based on unphased genotype data using a preliminary sample of unrelated subjects with an example from the Multiethnic Cohort Study
    Daniel 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...
  76. pmc Common SNPs in HMGCR in micronesians and whites associated with LDL-cholesterol levels affect alternative splicing of exon13
    Ralph Burkhardt
    Laboratory of Biochemical Genetics and Metabolism, The Rockefeller University, New York, NY 10065, USA
    Arterioscler Thromb Vasc Biol 28:2078-84. 2008
    ..Background- Variation in LDL-cholesterol (LDL-C) among individuals is a complex genetic trait involving multiple genes and gene-environment interactions...
  77. ncbi request reprint A comprehensive haplotype analysis of CYP19 and breast cancer risk: the Multiethnic Cohort
    Christopher A Haiman
    Department of Preventive Medicine, Keck School of Medicine, University of Southern California, USC Norris Comprehensive Cancer Center, 1441 Eastlake Ave, Rm 4441, Los Angeles, CA 90089 9175, USA
    Hum Mol Genet 12:2679-92. 2003
    ..31; 95% CI, 1.11-1.54). Our findings suggest the hypothesis that women with the long-range CYP19 haplotype 2b-3c may be carriers of a predisposing breast cancer susceptibility allele...
  78. ncbi request reprint Replicating genotype-phenotype associations
    Stephen J Chanock
    Division of Cancer Epidemiology and Genetics, Bethesda, Maryland 20892 4605, USA
    Nature 447:655-60. 2007
  79. pmc TXNIP regulates peripheral glucose metabolism in humans
    Hemang Parikh
    Department of Clinical Sciences, Diabetes and Endocrinology, Lund University, University Hospital Malmo, Malmo, Sweden
    PLoS Med 4:e158. 2007
    ..Impaired glucose uptake in skeletal muscle is believed to be one of the earliest features in the natural history of T2DM, although underlying mechanisms remain obscure...
  80. 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
    ....
  81. pmc Multiple regions within 8q24 independently affect risk for prostate cancer
    Christopher A Haiman
    Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California 90089, USA
    Nat Genet 39:638-44. 2007
    ..None of the prostate cancer risk variants aligns to a known gene or alters the coding sequence of an encoded protein...
  82. 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...
  83. pmc The case for selection at CCR5-Delta32
    Pardis C Sabeti
    Broad Institute of MIT and Harvard, Cambridge, Massachusetts, United States of America
    PLoS Biol 3:e378. 2005
    ..More broadly, the results have general implications for the design of future studies to detect the signs of positive selection in the human genome...
  84. 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...
  85. ncbi request reprint Common genetic variation in IGF1 and prostate cancer risk in the Multiethnic Cohort
    Iona Cheng
    Department of Preventive Medicine, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
    J Natl Cancer Inst 98:123-34. 2006
    ..Insulin-like growth factor I (IGF-I) appears to play a role in prostate development and carcinogenesis. We investigated whether genetic variation at the IGF1 locus is associated with prostate cancer risk...
  86. pmc TCF7L2 polymorphisms and progression to diabetes in the Diabetes Prevention Program
    Jose C Florez
    Diabetes Prevention Program Outcomes Study Coordinating Center, George Washington University, Rockville, MD 20852, USA
    N Engl J Med 355:241-50. 2006
    ....
  87. ncbi request reprint Guilt beyond a reasonable doubt
    David Altshuler
    Nat Genet 39:813-5. 2007
  88. pmc Genetic and functional analysis of CHEK2 (CHK2) variants in multiethnic cohorts
    Daphne W Bell
    Massachusetts General Hospital Cancer Center, Charlestown, MA, USA
    Int J Cancer 121:2661-7. 2007
    ....
  89. 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...
  90. pmc A high-density admixture map for disease gene discovery in african americans
    Michael W Smith
    Laboratory of Genomic Diversity, National Cancer Institute, Frederick, MD, USA
    Am J Hum Genet 74:1001-13. 2004
    ..The map is especially appropriate for those diseases that differ in incidence between the parental African and European populations...
  91. pmc Variations in the G6PC2/ABCB11 genomic region are associated with fasting glucose levels
    Wei Min Chen
    Department of Public Health Sciences, University of Virginia, Charlottesville, Virginia, USA
    J Clin Invest 118:2620-8. 2008
    ....
  92. doi request reprint Estimation of the multiple testing burden for genomewide association studies of nearly all common variants
    Itsik Pe'er
    Department of Computer Science, Columbia University, New York, New York, USA
    Genet Epidemiol 32:381-5. 2008
    ..We further identify the sensitivity of the testing burden to the required significance level, with implications to staged design of association studies...
  93. ncbi request reprint CYP17 genetic variation and risk of breast and prostate cancer from the National Cancer Institute Breast and Prostate Cancer Cohort Consortium (BPC3)
    Veronica Wendy Setiawan
    Department of Preventive Medicine, University of Southern California, Los Angeles, CA 90033, USA
    Cancer Epidemiol Biomarkers Prev 16:2237-46. 2007
    ..Our findings do not support the hypothesis that common germ line variation in CYP17 makes a substantial contribution to postmenopausal breast or prostate cancer susceptibility...
  94. ncbi request reprint The multiethnic cohort study: exploring genes, lifestyle and cancer risk
    Laurence N Kolonel
    Cancer Research Center, University of Hawaii, Honolulu, Hawaii 96813, USA
    Nat Rev Cancer 4:519-27. 2004
  95. pmc A second generation human haplotype map of over 3.1 million SNPs
    Kelly A Frazer
    The Scripps Research Institute, 10550 North Torrey Pines Road MEM275, La Jolla, California 92037, USA
    Nature 449:851-61. 2007
    ..Finally, we demonstrate increased differentiation at non-synonymous, compared to synonymous, SNPs, resulting from systematic differences in the strength or efficacy of natural selection between populations...
  96. ncbi request reprint Igf-I genetic variation and breast cancer: the multiethnic cohort
    Veronica Wendy Setiawan
    Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
    Cancer Epidemiol Biomarkers Prev 15:172-4. 2006
  97. 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...
  98. ncbi request reprint Haplotype analysis of the HSD17B1 gene and risk of breast cancer: a comprehensive approach to multicenter analyses of prospective cohort studies
    Heather Spencer Feigelson
    Department of Epidemiology and Surveillance Research, American Cancer Society, National Home Office, Atlanta, Georgia 30329, USA
    Cancer Res 66:2468-75. 2006
    ..Although the probability that these ER-negative findings are false-positive results is high, these findings were consistent across each cohort examined and warrant further study...

Research Grants14

  1. Human Genome Sequence Variation & the Inherited Basis
    David Altshuler; Fiscal Year: 2004
    ..abstract_text> ..
  2. COMMON VARIATION IN CANDIDATE GENES IN THE DPP
    David Altshuler; Fiscal Year: 2009
    ..If successful, the proposed research should help elucidate the genetic heterogeneity of T2D and obesity, as well as lay the foundation for pharmacogenetic studies of treatment response and prevention in T2D. ..
  3. A Genome-wide Association Study for Early-Onset Myocardial Infarction
    David Altshuler; Fiscal Year: 2009
    ..Successfully identifying common gene variants and novel pathways underlying risk of Ml has the potential to transform understanding, treatment, and prevention of the leading cause of death in the U.S. (End of Abstract) ..
  4. A Genome-wide Association Study for Early-Onset Myocardial Infarction
    David Altshuler; Fiscal Year: 2007
    ..Successfully identifying common gene variants and novel pathways underlying risk of Ml has the potential to transform understanding, treatment, and prevention of the leading cause of death in the U.S. (End of Abstract) ..
  5. Design/Production of Haplotype Map of the Human Genome
    David Altshuler; Fiscal Year: 2005
    ..The haplotype map project will catalyze human genetic studies of unprecedented power and scope, promising increased insight into disease risk in the population, and ultimately, improved clinical care. ..
  6. Genomic variation, hapmap and disease
    David Altshuler; Fiscal Year: 2006
    ..a scientific meeting ("Mining the HapMap") organized by leaders of the HapMap Project's analysis group (David Altshuler, Aravinda Chakravarti, Mark Daly, and Peter Donnelly) that follows on two highly successful meetings in 2004 ..
  7. Genome Sequence Variation
    David Altshuler; Fiscal Year: 2006
    ....