Whole-exome sequencing of 2,000 Danish individuals and the role of rare coding variants in type 2 diabetes

American Journal of Human Genetics

Volumn 93, Issue 6, 2013, Pages 1072-1086

  Lohmueller, Kirk E ^a,o   Sparsø, Thomas ^b   Li, Qibin ^c   Andersson, Ehm ^b   Korneliussen, Thorfinn ^d   Albrechtsen, Anders ^e   Banasik, Karina ^b   Grarup, Niels ^b   Hallgrimsdottir, Ingileif ^a   Kiil, Kristoffer ^b   Kilpeläinen, Tuomas O ^b   Krarup, Nikolaj T ^b   Pers, Tune H ^f,g,h   Sanchez, Gaston ^a   Hu, Youna ^a   Degiorgio, Michael ^a,p   Jørgensen, Torben ^i,j,k   Sandbæk, Annelli ^l   Lauritzen, Torsten ^l   Brunak, Søren ^f   Kristiansen, Karsten ^c,e   Li, Yingrui ^c   Hansen, Torben ^b,m   Wang, Jun ^b,c,e   Nielsen, Rasmus ^a,e   Pedersen, Oluf ^b,i,n   more..

^a UNIVERSITY OF CALIFORNIA   (United States)

^b Capital Region   (Denmark)

^c BGI SHENZHEN   (China)

^d UNIVERSITY OF COPENHAGEN   (Denmark)

^e UNIVERSITY OF COPENHAGEN   (Denmark)

^f TECHNICAL UNIVERSITY OF DENMARK   (Denmark)

^g MASSACHUSETTS INSTITUTE OF TECHNOLOGY   (United States)

^h BOSTON CHILDREN S HOSPITAL   (United States)

ⁱ UNIVERSITY OF COPENHAGEN   (Denmark)

^j AALBORG UNIVERSITY   (Denmark)

^k GLOSTRUP UNIVERSITY HOSPITAL   (Denmark)

^l AARHUS UNIVERSITY   (Denmark)

^m UNIVERSITY OF SOUTHERN DENMARK   (Denmark)

ⁿ AARHUS UNIVERSITY   (Denmark)

^o UNIVERSITY OF CALIFORNIA   (United States)

^p PENNSYLVANIA STATE UNIVERSITY   (United States)

more..

Author keywords

[No Author keywords available]

Indexed keywords

ARTICLE; BODY MASS; CONTROLLED STUDY; DENMARK; EXOME; GENE MUTATION; GENE SEQUENCE; GENETIC ASSOCIATION; GENETIC CODE; GENETIC SUSCEPTIBILITY; GENETIC VARIABILITY; GENOTYPE; HERITABILITY; HUMAN; HYPERTENSION; MAJOR CLINICAL STUDY; NON INSULIN DEPENDENT DIABETES MELLITUS; PRIORITY JOURNAL; SEQUENCE ANALYSIS; SIMULATION;

COMPUTATIONAL BIOLOGY; DENMARK; DIABETES MELLITUS, TYPE 2; EUROPEAN CONTINENTAL ANCESTRY GROUP; EXOME; GENETIC ASSOCIATION STUDIES; GENETIC VARIATION; GENOTYPE; HIGH-THROUGHPUT NUCLEOTIDE SEQUENCING; HUMANS; MODELS, STATISTICAL; OPEN READING FRAMES; POLYMORPHISM, SINGLE NUCLEOTIDE;

EID: 84890260477     PISSN: 00029297     EISSN: 15376605     Source Type: Journal    
DOI: 10.1016/j.ajhg.2013.11.005     Document Type: Article

References (83)

1. R.A. King, J.I. Rotter, and A.G. Motulsky The Genetic Basis of Common Diseases 2002 Oxford University Press New York, NY
2. N.J. Risch Searching for genetic determinants in the new millennium Nature 405 2000 847 856
3. B.E. Stranger, E.A. Stahl, and T. Raj Progress and promise of genome-wide association studies for human complex trait genetics Genetics 187 2011 367 383
4. D. Altshuler, M.J. Daly, and E.S. Lander Genetic mapping in human disease Science 322 2008 881 888
5. J.H. Park, S. Wacholder, M.H. Gail, U. Peters, K.B. Jacobs, S.J. Chanock, and N. Chatterjee Estimation of effect size distribution from genome-wide association studies and implications for future discoveries Nat. Genet. 42 2010 570 575
6. T.A. Manolio, F.S. Collins, N.J. Cox, D.B. Goldstein, L.A. Hindorff, D.J. Hunter, M.I. McCarthy, E.M. Ramos, L.R. Cardon, and A. Chakravarti Finding the missing heritability of complex diseases Nature 461 2009 747 753
7. E.E. Eichler, J. Flint, G. Gibson, A. Kong, S.M. Leal, J.H. Moore, and J.H. Nadeau Missing heritability and strategies for finding the underlying causes of complex disease Nat. Rev. Genet. 11 2010 446 450
8. G. Gibson Rare and common variants: twenty arguments Nat. Rev. Genet. 13 2011 135 145
9. E.T. Cirulli, and D.B. Goldstein Uncovering the roles of rare variants in common disease through whole-genome sequencing Nat. Rev. Genet. 11 2010 415 425
10. N.J. Schork, S.S. Murray, K.A. Frazer, and E.J. Topol Common vs. rare allele hypotheses for complex diseases Curr. Opin. Genet. Dev. 19 2009 212 219
11. A. Eyre-Walker Evolution in health and medicine Sackler colloquium: Genetic architecture of a complex trait and its implications for fitness and genome-wide association studies Proc. Natl. Acad. Sci. USA 107 Suppl 1 2010 1752 1756
12. J.K. Pritchard Are rare variants responsible for susceptibility to complex diseases? Am. J. Hum. Genet. 69 2001 124 137
13. N. Ahituv, N. Kavaslar, W. Schackwitz, A. Ustaszewska, J. Martin, S. Hebert, H. Doelle, B. Ersoy, G. Kryukov, and S. Schmidt Medical sequencing at the extremes of human body mass Am. J. Hum. Genet. 80 2007 779 791
14. J. Cohen, A. Pertsemlidis, I.K. Kotowski, R. Graham, C.K. Garcia, and H.H. Hobbs Low LDL cholesterol in individuals of African descent resulting from frequent nonsense mutations in PCSK9 Nat. Genet. 37 2005 161 165
15. J.C. Cohen, R.S. Kiss, A. Pertsemlidis, Y.L. Marcel, R. McPherson, and H.H. Hobbs Multiple rare alleles contribute to low plasma levels of HDL cholesterol Science 305 2004 869 872
16. S. Romeo, L.A. Pennacchio, Y. Fu, E. Boerwinkle, A. Tybjaerg-Hansen, H.H. Hobbs, and J.C. Cohen Population-based resequencing of ANGPTL4 uncovers variations that reduce triglycerides and increase HDL Nat. Genet. 39 2007 513 516
17. S. Nejentsev, N. Walker, D. Riches, M. Egholm, and J.A. Todd Rare variants of IFIH1, a gene implicated in antiviral responses, protect against type 1 diabetes Science 324 2009 387 389
18. A. Albrechtsen, N. Grarup, Y. Li, T. Sparsø, G. Tian, H. Cao, T. Jiang, S.Y. Kim, T. Korneliussen, Q. Li D.E.S.I.R. Study Group DIAGRAM Consortium Exome sequencing-driven discovery of coding polymorphisms associated with common metabolic phenotypes Diabetologia 56 2013 298 310
19. J. Shendure, and H. Ji Next-generation DNA sequencing Nat. Biotechnol. 26 2008 1135 1145
20. S.B. Ng, E.H. Turner, P.D. Robertson, S.D. Flygare, A.W. Bigham, C. Lee, T. Shaffer, M. Wong, A. Bhattacharjee, and E.E. Eichler Targeted capture and massively parallel sequencing of 12 human exomes Nature 461 2009 272 276
21. S.B. Ng, A.W. Bigham, K.J. Buckingham, M.C. Hannibal, M.J. McMillin, H.I. Gildersleeve, A.E. Beck, H.K. Tabor, G.M. Cooper, and H.C. Mefford Exome sequencing identifies MLL2 mutations as a cause of Kabuki syndrome Nat. Genet. 42 2010 790 793
22. S.B. Ng, D.A. Nickerson, M.J. Bamshad, and J. Shendure Massively parallel sequencing and rare disease Hum. Mol. Genet. 19 R2 2010 R119 R124
23. S.B. Ng, K.J. Buckingham, C. Lee, A.W. Bigham, H.K. Tabor, K.M. Dent, C.D. Huff, P.T. Shannon, E.W. Jabs, and D.A. Nickerson Exome sequencing identifies the cause of a Mendelian disorder Nat. Genet. 42 2010 30 35
24. M.J. Bamshad, S.B. Ng, A.W. Bigham, H.K. Tabor, M.J. Emond, D.A. Nickerson, and J. Shendure Exome sequencing as a tool for Mendelian disease gene discovery Nat. Rev. Genet. 12 2011 745 755
25. M.J. Bamshad, J.A. Shendure, D. Valle, A. Hamosh, J.R. Lupski, R.A. Gibbs, E. Boerwinkle, R.P. Lifton, M. Gerstein, M. Gunel Centers for Mendelian Genomics The Centers for Mendelian Genomics: A new large-scale initiative to identify the genes underlying rare Mendelian conditions Am. J. Med. Genet. A. 158A 2012 1523 1525
26. B. Li, and S.M. Leal Methods for detecting associations with rare variants for common diseases: Application to analysis of sequence data Am. J. Hum. Genet. 83 2008 311 321
27. D.J. Liu, and S.M. Leal A novel adaptive method for the analysis of next-generation sequencing data to detect complex trait associations with rare variants due to gene main effects and interactions PLoS Genet. 6 2010 e1001156
28. B.E. Madsen, and S.R. Browning A groupwise association test for rare mutations using a weighted sum statistic PLoS Genet. 5 2009 e1000384
29. M.C. Wu, S. Lee, T. Cai, Y. Li, M. Boehnke, and X. Lin Rare-variant association testing for sequencing data with the sequence kernel association test Am. J. Hum. Genet. 89 2011 82 93
30. J. Asimit, and E. Zeggini Rare variant association analysis methods for complex traits Annu. Rev. Genet. 44 2010 293 308
31. W. Pan, S. Basu, and X. Shen Adaptive tests for detecting gene-gene and gene-environment interactions Hum. Hered. 72 2011 98 109
32. M.A. Permutt, J. Wasson, and N. Cox Genetic epidemiology of diabetes J. Clin. Invest. 115 2005 1431 1439
33. P. Almgren, M. Lehtovirta, B. Isomaa, L. Sarelin, M.R. Taskinen, V. Lyssenko, T. Tuomi, L. Groop Botnia Study Group Heritability and familiality of type 2 diabetes and related quantitative traits in the Botnia Study Diabetologia 54 2011 2811 2819
34. J. Kaprio, J. Tuomilehto, M. Koskenvuo, K. Romanov, A. Reunanen, J. Eriksson, J. Stengård, and Y.A. Kesäniemi Concordance for type 1 (insulin-dependent) and type 2 (non-insulin-dependent) diabetes mellitus in a population-based cohort of twins in Finland Diabetologia 35 1992 1060 1067
35. P. Poulsen, K.O. Kyvik, A. Vaag, and H. Beck-Nielsen Heritability of type II (non-insulin-dependent) diabetes mellitus and abnormal glucose tolerance - a population-based twin study Diabetologia 42 1999 139 145
36. A.P. Morris, B.F. Voight, T.M. Teslovich, T. Ferreira, A.V. Segrè, V. Steinthorsdottir, R.J. Strawbridge, H. Khan, H. Grallert, A. Mahajan Wellcome Trust Case Control Consortium Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC) Investigators Genetic Investigation of ANthropometric Traits (GIANT) Consortium Asian Genetic Epidemiology Network-Type 2 Diabetes (AGEN-T2D) Consortium South Asian Type 2 Diabetes (SAT2D) Consortium DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) Consortium Large-scale association analysis provides insights into the genetic architecture and pathophysiology of type 2 diabetes Nat. Genet. 44 2012 981 990
37. K.G. Alberti, and P.Z. Zimmet Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus provisional report of a WHO consultation Diabet. Med. 15 1998 539 553
38. T. Jørgensen, K. Borch-Johnsen, T.F. Thomsen, H. Ibsen, C. Glümer, and C. Pisinger A randomized non-pharmacological intervention study for prevention of ischaemic heart disease: baseline results Inter99 Eur. J. Cardiovasc. Prev. Rehabil. 10 2003 377 386
39. C. Glümer, T. Jørgensen, K. Borch-Johnsen Inter99 study Prevalences of diabetes and impaired glucose regulation in a Danish population: The Inter99 study Diabetes Care 26 2003 2335 2340
40. T. Lauritzen, S. Griffin, K. Borch-Johnsen, N.J. Wareham, B.H. Wolffenbuttel, G. Rutten Anglo-Danish-Dutch Study of Intensive Treatment in People with Screen Detected Diabetes in Primary Care The ADDITION study: proposed trial of the cost-effectiveness of an intensive multifactorial intervention on morbidity and mortality among people with Type 2 diabetes detected by screening Int. J. Obes. Relat. Metab. Disord. 24 Suppl 3 2000 S6 S11
41. H. Li, and R. Durbin Fast and accurate long-read alignment with Burrows-Wheeler transform Bioinformatics 26 2010 589 595
42. H. Li, B. Handsaker, A. Wysoker, T. Fennell, J. Ruan, N. Homer, G. Marth, G. Abecasis, R. Durbin 1000 Genome Project Data Processing Subgroup The Sequence Alignment/Map format and SAMtools Bioinformatics 25 2009 2078 2079
43. S.Y. Kim, K.E. Lohmueller, A. Albrechtsen, Y. Li, T. Korneliussen, G. Tian, N. Grarup, T. Jiang, G. Andersen, and D. Witte Estimation of allele frequency and association mapping using next-generation sequencing data BMC Bioinformatics 12 2011 231
44. L. Skotte, T.S. Korneliussen, and A. Albrechtsen Association testing for next-generation sequencing data using score statistics Genet. Epidemiol. 36 2012 430 437
45. R. Nielsen, T. Korneliussen, A. Albrechtsen, Y. Li, and J. Wang SNP calling, genotype calling, and sample allele frequency estimation from new-generation sequencing data PLoS ONE 7 2012 e37558
46. B.L. Browning, and Z. Yu Simultaneous genotype calling and haplotype phasing improves genotype accuracy and reduces false-positive associations for genome-wide association studies Am. J. Hum. Genet. 85 2009 847 861
47. G.R. Abecasis, A. Auton, L.D. Brooks, M.A. DePristo, R.M. Durbin, R.E. Handsaker, H.M. Kang, G.T. Marth, G.A. McVean 1000 Genomes Project Consortium An integrated map of genetic variation from 1,092 human genomes Nature 491 2012 56 65
48. K. Lage, E.O. Karlberg, Z.M. Størling, P.I. Olason, A.G. Pedersen, O. Rigina, A.M. Hinsby, Z. Tümer, F. Pociot, and N. Tommerup A human phenome-interactome network of protein complexes implicated in genetic disorders Nat. Biotechnol. 25 2007 309 316
49. A.I. Su, T. Wiltshire, S. Batalov, H. Lapp, K.A. Ching, D. Block, J. Zhang, R. Soden, M. Hayakawa, and G. Kreiman A gene atlas of the mouse and human protein-encoding transcriptomes Proc. Natl. Acad. Sci. USA 101 2004 6062 6067
50. S. Purcell, B. Neale, K. Todd-Brown, L. Thomas, M.A. Ferreira, D. Bender, J. Maller, P. Sklar, P.I. de Bakker, M.J. Daly, and P.C. Sham PLINK: A tool set for whole-genome association and population-based linkage analyses Am. J. Hum. Genet. 81 2007 559 575
51. R. Do, S. Kathiresan, and G.R. Abecasis Exome sequencing and complex disease: practical aspects of rare variant association studies Hum. Mol. Genet. 21 R1 2012 R1 R9
52. A.L. Price, G.V. Kryukov, P.I. de Bakker, S.M. Purcell, J. Staples, L.J. Wei, and S.R. Sunyaev Pooled association tests for rare variants in exon-resequencing studies Am. J. Hum. Genet. 86 2010 832 838
53. A. Kiezun, K. Garimella, R. Do, N.O. Stitziel, B.M. Neale, P.J. McLaren, N. Gupta, P. Sklar, P.F. Sullivan, and J.L. Moran Exome sequencing and the genetic basis of complex traits Nat. Genet. 44 2012 623 630
54. A.D. Long, and C.H. Langley The power of association studies to detect the contribution of candidate genetic loci to variation in complex traits Genome Res. 9 1999 720 731
55. G. Pilia, W.M. Chen, A. Scuteri, M. Orrú, G. Albai, M. Dei, S. Lai, G. Usala, M. Lai, and P. Loi Heritability of cardiovascular and personality traits in 6,148 Sardinians PLoS Genet. 2 2006 e132
56. J. Yang, S.H. Lee, M.E. Goddard, and P.M. Visscher GCTA: A tool for genome-wide complex trait analysis Am. J. Hum. Genet. 88 2011 76 82
57. M.N. Bainbridge, M. Wang, Y. Wu, I. Newsham, D.M. Muzny, J.L. Jefferies, T.J. Albert, D.L. Burgess, and R.A. Gibbs Targeted enrichment beyond the consensus coding DNA sequence exome reveals exons with higher variant densities Genome Biol. 12 2011 R68
58. J.A. Tennessen, A.W. Bigham, T.D. O'Connor, W. Fu, E.E. Kenny, S. Gravel, S. McGee, R. Do, X. Liu, G. Jun Broad GO Seattle GO NHLBI Exome Sequencing Project Evolution and functional impact of rare coding variation from deep sequencing of human exomes Science 337 2012 64 69
59. D. Challis, J. Yu, U.S. Evani, A.R. Jackson, S. Paithankar, C. Coarfa, A. Milosavljevic, R.A. Gibbs, and F. Yu An integrative variant analysis suite for whole exome next-generation sequencing data BMC Bioinformatics 13 2012 8
60. S. Ellard, and K. Colclough Mutations in the genes encoding the transcription factors hepatocyte nuclear factor 1 alpha (HNF1A) and 4 alpha (HNF4A) in maturity-onset diabetes of the young Hum. Mutat. 27 2006 854 869
61. K.K. Osbak, K. Colclough, C. Saint-Martin, N.L. Beer, C. Bellanné-Chantelot, S. Ellard, and A.L. Gloyn Update on mutations in glucokinase (GCK), which cause maturity-onset diabetes of the young, permanent neonatal diabetes, and hyperinsulinemic hypoglycemia Hum. Mutat. 30 2009 1512 1526
62. I.P. Gorlov, O.Y. Gorlova, S.R. Sunyaev, M.R. Spitz, and C.I. Amos Shifting paradigm of association studies: value of rare single-nucleotide polymorphisms Am. J. Hum. Genet. 82 2008 100 112
63. H. Lango Allen, K. Estrada, G. Lettre, S.I. Berndt, M.N. Weedon, F. Rivadeneira, C.J. Willer, A.U. Jackson, S. Vedantam, and S. Raychaudhuri Hundreds of variants clustered in genomic loci and biological pathways affect human height Nature 467 2010 832 838
64. M.V. Rockman The QTN program and the alleles that matter for evolution: All that's gold does not glitter Evolution 66 2012 1 17
65. H.A. Orr The population genetics of adaptation: The distribution of factors fixed during adaptive evolution Evolution 52 1998 935 949
66. W.G. Hill, M.E. Goddard, and P.M. Visscher Data and theory point to mainly additive genetic variance for complex traits PLoS Genet. 4 2008 e1000008
67. K.R. Thornton, A.J. Foran, and A.D. Long Properties and modeling of GWAS when complex disease risk is due to non-complementing, deleterious mutations in genes of large effect PLoS Genet. 9 2013 e1003258
68. Y. Li, N. Vinckenbosch, G. Tian, E. Huerta-Sanchez, T. Jiang, H. Jiang, A. Albrechtsen, G. Andersen, H. Cao, and T. Korneliussen Resequencing of 200 human exomes identifies an excess of low-frequency non-synonymous coding variants Nat. Genet. 42 2010 969 972
69. E.A. Stahl, D. Wegmann, G. Trynka, J. Gutierrez-Achury, R. Do, B.F. Voight, P. Kraft, R. Chen, H.J. Kallberg, F.A. Kurreeman Diabetes Genetics Replication and Meta-analysis Consortium Myocardial Infarction Genetics Consortium Bayesian inference analyses of the polygenic architecture of rheumatoid arthritis Nat. Genet. 44 2012 483 489
70. S. Vattikuti, J. Guo, and C.C. Chow Heritability and genetic correlations explained by common SNPs for metabolic syndrome traits PLoS Genet. 8 2012 e1002637
71. J. Yang, T.A. Manolio, L.R. Pasquale, E. Boerwinkle, N. Caporaso, J.M. Cunningham, M. de Andrade, B. Feenstra, E. Feingold, and M.G. Hayes Genome partitioning of genetic variation for complex traits using common SNPs Nat. Genet. 43 2011 519 525
72. O. Zuk, E. Hechter, S.R. Sunyaev, and E.S. Lander The mystery of missing heritability: Genetic interactions create phantom heritability Proc. Natl. Acad. Sci. USA 109 2012 1193 1198
73. S.P. Dickson, K. Wang, I. Krantz, H. Hakonarson, and D.B. Goldstein Rare variants create synthetic genome-wide associations PLoS Biol. 8 2010 e1000294
74. D. Chang, and A. Keinan Predicting signatures of "synthetic associations" and "natural associations" from empirical patterns of human genetic variation PLoS Comput. Biol. 8 2012 e1002600
75. J. McClellan, and M.C. King Genetic heterogeneity in human disease Cell 141 2010 210 217
76. J.R. Lupski, J.W. Belmont, E. Boerwinkle, and R.A. Gibbs Clan genomics and the complex architecture of human disease Cell 147 2011 32 43
77. A.C. Need, J.P. McEvoy, M. Gennarelli, E.L. Heinzen, D. Ge, J.M. Maia, K.V. Shianna, M. He, E.T. Cirulli, and C.E. Gumbs Exome sequencing followed by large-scale genotyping suggests a limited role for moderately rare risk factors of strong effect in schizophrenia Am. J. Hum. Genet. 91 2012 303 312
78. E.L. Heinzen, C. Depondt, G.L. Cavalleri, E.K. Ruzzo, N.M. Walley, A.C. Need, D. Ge, M. He, E.T. Cirulli, and Q. Zhao Exome sequencing followed by large-scale genotyping fails to identify single rare variants of large effect in idiopathic generalized epilepsy Am. J. Hum. Genet. 91 2012 293 302
79. L. Liu, A. Sabo, B.M. Neale, U. Nagaswamy, C. Stevens, E. Lim, C.A. Bodea, D. Muzny, J.G. Reid, and E. Banks Analysis of rare, exonic variation amongst subjects with autism spectrum disorders and population controls PLoS Genet. 9 2013 e1003443
80. K.A. Hunt, V. Mistry, N.A. Bockett, T. Ahmad, M. Ban, J.N. Barker, J.C. Barrett, H. Blackburn, O. Brand, and O. Burren Negligible impact of rare autoimmune-locus coding-region variants on missing heritability Nature 498 2013 232 235
81. H. Helgason, P. Sulem, M.R. Duvvari, H. Luo, G. Thorleifsson, H. Stefansson, I. Jonsdottir, G. Masson, D.F. Gudbjartsson, and G.B. Walters A rare nonsynonymous sequence variant in C3 is associated with high risk of age-related macular degeneration Nat. Genet. 45 2013 1371 1374
82. J.M. Seddon, Y. Yu, E.C. Miller, R. Reynolds, P.L. Tan, S. Gowrisankar, J.I. Goldstein, M. Triebwasser, H.E. Anderson, and J. Zerbib Rare variants in CFI, C3 and C9 are associated with high risk of advanced age-related macular degeneration Nat. Genet. 45 2013 1366 1370
83. X. Zhan, D.E. Larson, C. Wang, D.C. Koboldt, Y.V. Sergeev, R.S. Fulton, L.L. Fulton, C.C. Fronick, K.E. Branham, and J. Bragg-Gresham Identification of a rare coding variant in complement 3 associated with age-related macular degeneration Nat. Genet. 45 2013 1375 1379