DF/HCC Program Affiliation

Member, Prostate Cancer Program
Member, Cancer Genetics Program

Research Abstract

Dr. Altshuler’s research focused on two main goals: to characterize and catalogue human genome sequence variation, and to apply these insights, data and methods to illuminate the inherited basis of common, polygenic diseases. Dr. Altshuler is currently principal investigator on grants or subcontracts contributing to the Haplotype Map of the human genome (NHGRI, NIH), the Cohort Consortium for Prostate and Breast Cancer (NCI), the Multiethnic Cohort (NCI), the Diabetes Genome Anatomy Project (NIDDK, NIH), and six other funded projects. In 2002 Dr. Altshuler was named a Clinical Scholar in Translational Research of the Burroughs Welcome Fund, a Charles E. Culpeper Scholar of the Rockefeller Brother’s Fund, and the Krane Award of the MGH. Dr. Altshuler is an advisor to the National Institutes of Health, Merck Research Laboratories, The Wellcome Trust, and the Doris Duke Charitable Foundation.

Publications

• , Chanock SJ, Manolio T, Boehnke M, Boerwinkle E, Hunter DJ, Thomas G, Hirschhorn JN, Abecasis G, Altshuler D, Bailey-Wilson JE, Brooks LD, Cardon LR, Daly M, Donnelly P, Fraumeni JF, Freimer NB, Gerhard DS, Gunter C, Guttmacher AE, Guyer MS, Harris EL,. Replicating genotype-phenotype associations. Nature 2007 Jun 7; 447(7145):655-60
  PMID: 17554299
• , Eichler EE, Nickerson DA, Altshuler D, Bowcock AM, Brooks LD, Carter NP, Church DM, Felsenfeld A, Guyer M, Lee C, Lupski JR, Mullikin JC, Pritchard JK, Sebat J, Sherry ST, Smith D, Valle D, Waterston RH. Completing the map of human genetic variation. Nature 2007 May 10; 447(7141):161-5
  PMID: 17495918
• Saxena R, Voight BF, Lyssenko V, Burtt NP, de Bakker PI, Chen H, Roix JJ, Kathiresan S, Hirschhorn JN, Daly MJ, Hughes TE, Groop L, Altshuler D, Almgren P, Florez JC, Meyer J, Ardlie K, Bengtsson K, Isomaa B, Lettre G, Lindblad U, Lyon HN, Melander O, New. Genome-Wide Association Analysis Identifies Loci for Type 2 Diabetes and Triglyceride Levels. Science 2007 Apr 26;
  PMID: 17463246
• Florez JC, Sjögren M, Agapakis CM, Burtt NP, Almgren P, Lindblad U, Berglund G, Tuomi T, Gaudet D, Daly MJ, Ardlie KG, Hirschhorn JN, Altshuler D, Groop L. Association testing of common variants in the insulin receptor substrate-1 gene (IRS1) with type 2 diabetes. Diabetologia 2007 Apr 19;
  PMID: 17443311
• Graham RR, Kyogoku C, Sigurdsson S, Vlasova IA, Davies LR, Baechler EC, Plenge RM, Koeuth T, Ortmann WA, Hom G, Bauer JW, Gillett C, Burtt N, Cunninghame Graham DS, Onofrio R, Petri M, Gunnarsson I, Svenungsson E, Rönnblom L, Nordmark G, Gregersen PK, Mos. Three functional variants of IFN regulatory factor 5 (IRF5) define risk and protective haplotypes for human lupus. Proc Natl Acad Sci U S A 2007 Apr 17; 104(16):6758-63
  PMID: 17412832
• Sekine H, Ferreira RC, Pan-Hammarström Q, Graham RR, Ziemba B, de Vries SS, Liu J, Hippen K, Koeuth T, Ortmann W, Iwahori A, Elliott MK, Offer S, Skon C, Du L, Novitzke J, Lee AT, Zhao N, Tompkins JD, Altshuler D, Gregersen PK, Cunningham-Rundles C, Harri. Role for Msh5 in the regulation of Ig class switch recombination. Proc Natl Acad Sci U S A 2007 Apr 24; 104(17):7193-8
  PMID: 17409188
• Haiman CA, Patterson N, Freedman ML, Myers SR, Pike MC, Waliszewska A, Neubauer J, Tandon A, Schirmer C, McDonald GJ, Greenway SC, Stram DO, Le Marchand L, Kolonel LN, Frasco M, Wong D, Pooler LC, Ardlie K, Oakley-Girvan I, Whittemore AS, Cooney KA, John. Multiple regions within 8q24 independently affect risk for prostate cancer. Nat Genet 2007 May; 39(5):638-44
  PMID: 17401364
• Winckler W, Weedon MN, Graham RR, McCarroll SA, Purcell S, Almgren P, Tuomi T, Gaudet D, Boström KB, Walker M, Hitman G, Hattersley AT, McCarthy MI, Ardlie KG, Hirschhorn JN, Daly MJ, Frayling TM, Groop L, Altshuler D. Evaluation of common variants in the six known maturity-onset diabetes of the young (MODY) genes for association with type 2 diabetes. Diabetes 2007 Mar; 56(3):685-93
  PMID: 17327436
• Haiman CA, Dossus L, Setiawan VW, Stram DO, Dunning AM, Thomas G, Thun MJ, Albanes D, Altshuler D, Ardanaz E, Boeing H, Buring J, Burtt N, Calle EE, Chanock S, Clavel-Chapelon F, Colditz GA, Cox DG, Feigelson HS, Hankinson SE, Hayes RB, Henderson BE, Hirs. Genetic variation at the CYP19A1 locus predicts circulating estrogen levels but not breast cancer risk in postmenopausal women. Cancer Res 2007 Mar 1; 67(5):1893-7
  PMID: 17325027
• Florez JC, Jablonski KA, Kahn SE, Franks PW, Dabelea D, Hamman RF, Knowler WC, Nathan DM, Altshuler D. Type 2 diabetes-associated missense polymorphisms KCNJ11 E23K and ABCC8 A1369S influence progression to diabetes and response to interventions in the Diabetes Prevention Program. Diabetes 2007 Feb; 56(2):531-6
  PMID: 17259403
• Florez JC, Jablonski KA, Sun MW, Bayley N, Kahn SE, Shamoon H, Hamman RF, Knowler WC, Nathan DM, Altshuler D,. Effects of the type 2 diabetes-associated PPARG P12A polymorphism on progression to diabetes and response to troglitazone. J Clin Endocrinol Metab 2007 Apr; 92(4):1502-9
  PMID: 17213274
• Setiawan VW, Cheng I, Stram DO, Giorgi E, Pike MC, Van Den Berg D, Pooler L, Burtt NP, Le Marchand L, Altshuler D, Hirschhorn J, Henderson BE, Haiman CA. A systematic assessment of common genetic variation in CYP11A and risk of breast cancer. Cancer Res 2006 Dec 15; 66(24):12019-25
  PMID: 17178901
• Florez JC, Saxena R, Winckler W, Burtt NP, Almgren P, Bengtsson Boström K, Tuomi T, Gaudet D, Ardlie KG, Daly MJ, Altshuler D, Hirschhorn JN, Groop L. The Krüppel-like factor 11 (KLF11) Q62R polymorphism is not associated with type 2 diabetes in 8,676 people. Diabetes 2006 Dec; 55(12):3620-4
  PMID: 17130512
• De Bakker PI, Graham RR, Altshuler D, Henderson BE, Haiman CA. Transferability of tag SNPs to capture common genetic variation in DNA repair genes across multiple populations. Pac Symp Biocomput 2006; :478-86
  PMID: 17094262
• Lyon HN, Florez JC, Bersaglieri T, Saxena R, Winckler W, Almgren P, Lindblad U, Tuomi T, Gaudet D, Zhu X, Cooper R, Ardlie KG, Daly MJ, Altshuler D, Groop L, Hirschhorn JN. Common variants in the ENPP1 gene are not reproducibly associated with diabetes or obesity. Diabetes 2006 Nov; 55(11):3180-4
  PMID: 17065359
• de Bakker PI, Burtt NP, Graham RR, Guiducci C, Yelensky R, Drake JA, Bersaglieri T, Penney KL, Butler J, Young S, Onofrio RC, Lyon HN, Stram DO, Haiman CA, Freedman ML, Zhu X, Cooper R, Groop L, Kolonel LN, Henderson BE, Daly MJ, Hirschhorn JN, Altshuler. Transferability of tag SNPs in genetic association studies in multiple populations. Nat Genet 2006 Nov; 38(11):1298-303
  PMID: 17057720
• Holmkvist J, Cervin C, Lyssenko V, Winckler W, Anevski D, Cilio C, Almgren P, Berglund G, Nilsson P, Tuomi T, Lindgren CM, Altshuler D, Groop L. Common variants in HNF-1 alpha and risk of type 2 diabetes. Diabetologia 2006 Dec; 49(12):2882-91
  PMID: 17033837
• Saxena R, Gianniny L, Burtt NP, Lyssenko V, Giuducci C, Sjögren M, Florez JC, Almgren P, Isomaa B, Orho-Melander M, Lindblad U, Daly MJ, Tuomi T, Hirschhorn JN, Ardlie KG, Groop LC, Altshuler D. Common single nucleotide polymorphisms in TCF7L2 are reproducibly associated with type 2 diabetes and reduce the insulin response to glucose in nondiabetic individuals. Diabetes 2006 Oct; 55(10):2890-5
  PMID: 17003358
• Freedman ML, Haiman CA, Patterson N, McDonald GJ, Tandon A, Waliszewska A, Penney K, Steen RG, Ardlie K, John EM, Oakley-Girvan I, Whittemore AS, Cooney KA, Ingles SA, Altshuler D, Henderson BE, Reich D. From the Cover: Admixture mapping identifies 8q24 as a prostate cancer risk locus in African-American men. Proc Natl Acad Sci U S A 2006 Sep 19; 103(38):14068-73
  PMID: 16945910
• Maller J, George S, Purcell S, Fagerness J, Altshuler D, Daly MJ, Seddon JM. Common variation in three genes, including a noncoding variant in CFH, strongly influences risk of age-related macular degeneration. Nat Genet 2006 Sep; 38(9):1055-9
  PMID: 16936732
• Florez JC, Jablonski KA, Bayley N, Pollin TI, de Bakker PI, Shuldiner AR, Knowler WC, Nathan DM, Altshuler D,. TCF7L2 polymorphisms and progression to diabetes in the Diabetes Prevention Program. N Engl J Med 2006 Jul 20; 355(3):241-50
  PMID: 16855264
• Locke DP, Sharp AJ, McCarroll SA, McGrath SD, Newman TL, Cheng Z, Schwartz S, Albertson DG, Pinkel D, Altshuler DM, Eichler EE. Linkage Disequilibrium and Heritability of Copy-Number Polymorphisms within Duplicated Regions of the Human Genome. Am J Hum Genet 2006 Aug; 79(2):275-90
  PMID: 16826518
• Freeman JL, Perry GH, Feuk L, Redon R, McCarroll SA, Altshuler DM, Aburatani H, Jones KW, Tyler-Smith C, Hurles ME, Carter NP, Scherer SW, Lee C. Copy number variation: New insights in genome diversity. Genome Res 2006 Jun 29;
  PMID: 16809666
• Sabeti PC, Schaffner SF, Fry B, Lohmueller J, Varilly P, Shamovsky O, Palma A, Mikkelsen TS, Altshuler D, Lander ES. Positive natural selection in the human lineage. Science 2006 Jun 16; 312(5780):1614-20
  PMID: 16778047
• Saxena R, de Bakker PI, Singer K, Mootha V, Burtt N, Hirschhorn JN, Gaudet D, Isomaa B, Daly MJ, Groop L, Ardlie KG, Altshuler D. Comprehensive association testing of common mitochondrial DNA variation in metabolic disease. Am J Hum Genet 2006 Jul; 79(1):54-61
  PMID: 16773565
• Pe'er I, de Bakker PI, Maller J, Yelensky R, Altshuler D, Daly MJ. Evaluating and improving power in whole-genome association studies using fixed marker sets. Nat Genet 2006 Jun; 38(6):663-667
  PMID: 16715096
• Graham RR, Kozyrev SV, Baechler EC, Reddy MV, Plenge RM, Bauer JW, Ortmann WA, Koeuth T, Escribano MF, Collaborative Groups TA, Pons-Estel B, Petri M, Daly M, Gregersen PK, Martín J, Altshuler D, Behrens TW, Alarcón-Riquelme ME. A common haplotype of interferon regulatory factor 5 (IRF5) regulates splicing and expression and is associated with increased risk of systemic lupus erythematosus. Nat Genet 2006 May; 38(5):550-555
  PMID: 16642019
• Pe'er I, Chretien YR, de Bakker PI, Barrett JC, Daly MJ, Altshuler DM. Biases and reconciliation in estimates of linkage disequilibrium in the human genome. Am J Hum Genet 2006 Apr; 78(4):588-603
  PMID: 16532390
• Sun MW, Lee JY, de Bakker PI, Burtt NP, Almgren P, Råstam L, Tuomi T, Gaudet D, Daly MJ, Hirschhorn JN, Altshuler D, Groop L, Florez JC. Haplotype structures and large-scale association testing of the 5' AMP-activated protein kinase genes PRKAA2, PRKAB1, and PRKAB2 [corrected] with type 2 diabetes. Diabetes 2006 Mar; 55(3):849-55
  PMID: 16505254
• Feigelson HS, Cox DG, Cann HM, Wacholder S, Kaaks R, Henderson BE, Albanes D, Altshuler D, Berglund G, Berrino F, Bingham S, Buring JE, Burtt NP, Calle EE, Chanock SJ, Clavel-Chapelon F, Colditz G, Diver WR, Freedman ML, Haiman CA, Hankinson SE, Hayes RB,. Haplotype analysis of the HSD17B1 gene and risk of breast cancer: a comprehensive approach to multicenter analyses of prospective cohort studies. Cancer Res 2006 Feb 15; 66(4):2468-75
  PMID: 16489054
• McCarroll SA, Hadnott TN, Perry GH, Sabeti PC, Zody MC, Barrett JC, Dallaire S, Gabriel SB, Lee C, Daly MJ, Altshuler DM,. Common deletion polymorphisms in the human genome. Nat Genet 2006 Jan; 38(1):86-92
  PMID: 16468122
• Setiawan VW, Cheng I, Stram DO, Penney KL, Le Marchand L, Altshuler D, Kolonel LN, Hirschhorn J, Henderson BE, Freedman ML. Igf-I genetic variation and breast cancer: the multiethnic cohort. Cancer Epidemiol Biomarkers Prev 2006 Jan; 15(1):172-4
  PMID: 16434607
• Bonnen PE, Pe'er I, Plenge RM, Salit J, Lowe JK, Shapero MH, Lifton RP, Breslow JL, Daly MJ, Reich DE, Jones KW, Stoffel M, Altshuler D, Friedman JM. Evaluating potential for whole-genome studies in Kosrae, an isolated population in Micronesia. Nat Genet 2006 Feb; 38(2):214-7
  PMID: 16429162
• Cheng I, Stram DO, Penney KL, Pike M, Le Marchand L, Kolonel LN, Hirschhorn J, Altshuler D, Henderson BE, Freedman ML. Common genetic variation in IGF1 and prostate cancer risk in the Multiethnic Cohort. J Natl Cancer Inst 2006 Jan 18; 98(2):123-34
  PMID: 16418515
• Plenge RM, Padyukov L, Remmers EF, Purcell S, Lee AT, Karlson EW, Wolfe F, Kastner DL, Alfredsson L, Altshuler D, Gregersen PK, Klareskog L, Rioux JD. 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. Am J Hum Genet 2005 Dec; 77(6):1044-60
  PMID: 16380915
• Florez JC, Wiltshire S, Agapakis CM, Burtt NP, de Bakker PI, Almgren P, Bengtsson Boström K, Tuomi T, Gaudet D, Daly MJ, Hirschhorn JN, McCarthy MI, Altshuler D, Groop L. High-density haplotype structure and association testing of the insulin-degrading enzyme (IDE) gene with type 2 diabetes in 4,206 people. Diabetes 2006 Jan; 55(1):128-35
  PMID: 16380485
• Walsh EC, Sabeti P, Hutcheson HB, Fry B, Schaffner SF, de Bakker PI, Varilly P, Palma AA, Roy J, Cooper R, Winkler C, Zeng Y, de The G, Lander ES, O'brien S, Altshuler D. Searching for signals of evolutionary selection in 168 genes related to immune function. Hum Genet 2006 Mar; 119(1-2):92-102
  PMID: 16362345
• Altshuler D, Brooks LD, Chakravarti A, Collins FS, Daly MJ, Donnelly P,. A haplotype map of the human genome. Nature 2005 Oct 27; 437(7063):1299-320
  PMID: 16255080
• de Bakker PI, Yelensky R, Pe'er I, Gabriel SB, Daly MJ, Altshuler D. Efficiency and power in genetic association studies. Nat Genet 2005 Nov; 37(11):1217-1223
  PMID: 16244653
• Freedman ML, Penney KL, Stram DO, Riley S, McKean-Cowdin R, Le Marchand L, Altshuler D, Haiman CA. A haplotype-based case-control study of BRCA1 and sporadic breast cancer risk. Cancer Res 2005 Aug 15; 65(16):7516-22
  PMID: 16103107
• Reich DE, Schaffner SF, Daly MJ, McVean G, Mullikin JC, Higgins JM, Richter DJ, Lander ES, Altshuler D. Human genome sequence variation and the influence of gene history, mutation and recombination. Nat Genet 2002 Sep; 32(1):135-42
  PMID: 12161752
• Gabriel SB, Schaffner SF, Nguyen H, Moore JM, Roy J, Blumenstiel B, Higgins J, DeFelice M, Lochner A, Faggart M, Liu-Cordero SN, Rotimi C, Adeyemo A, Cooper R, Ward R, Lander ES, Daly MJ, Altshuler D. The structure of haplotype blocks in the human genome. Science 2002 Jun 21; 296(5576):2225-9
  PMID: 12029063
• Altshuler D, Hirschhorn JN, Klannemark M, Lindgren CM, Vohl MC, Nemesh J, Lane CR, Schaffner SF, Bolk S, Brewer C, Tuomi T, Gaudet D, Hudson TJ, Daly M, Groop L, Lander ES. The common PPARgamma Pro12Ala polymorphism is associated with decreased risk of type 2 diabetes. Nat Genet 2000 Sep; 26(1):76-80
  PMID: 10973253
• Cargill M, Altshuler D, Ireland J, Sklar P, Ardlie K, Patil N, Shaw N, Lane CR, Lim EP, Kalyanaraman N, Nemesh J, Ziaugra L, Friedland L, Rolfe A, Warrington J, Lipshutz R, Daley GQ, Lander ES. Characterization of single-nucleotide polymorphisms in coding regions of human genes. Nat Genet 1999 Jul; 22(3):231-8
  PMID: 10391209