Altshuler, D. et al. A haplotype map of the human genome. Nature437, 1299–1320 (2005). Google Scholar
Frazer, K. A. et al. A second generation human haplotype map of over 3.1 million SNPs. Nature449, 851–861 (2007). Publication of the HapMap Phase II results genotyping over 3.1 million SNPs in 270 individuals from four geographically diverse populations. CASPubMed Google Scholar
Hinds, D. A. et al. Whole-genome patterns of common DNA variation in three human populations. Science307, 1072–1079 (2005). CASPubMed Google Scholar
Sebat, J. et al. Large-scale copy number polymorphism in the human genome. Science305, 525–528 (2004). ArticleCASPubMed Google Scholar
Iafrate, A. J. et al. Detection of large-scale variation in the human genome. Nature Genet.36, 949–951 (2004). CASPubMed Google Scholar
Kidd, J. M. et al. Mapping and sequencing of structural variation from eight human genomes. Nature453, 56–64 (2008). Demonstrates the prevalence and importance of structural variation in the human genome, which historically had not been given much attention. CASPubMedPubMed Central Google Scholar
Levy, S. et al. The diploid genome sequence of an individual human. PLoS Biol.5, e254 (2007). The first publication of a genome sequence of a single individual (J. Craig Venter). PubMedPubMed Central Google Scholar
Wheeler, D. A. et al. The complete genome of an individual by massively parallel DNA sequencing. Nature452, 872–876 (2008). The first paper to demonstrate how technological advances will enable the rapid sequencing of individual human genomes in the near future. Interestingly, the individual sequenced here is Jim Watson, who won the nobel prize for discovery of the DNA double helix. CASPubMed Google Scholar
Bentley, D. R. et al. Accurate whole human genome sequencing using reversible terminator chemistry. Nature456, 53–59 (2008). CASPubMedPubMed Central Google Scholar
McCarthy, M. I. et al. Genome-wide association studies for complex traits: consensus, uncertainty and challenges. Nature Rev. Genet.9, 356–369 (2008). A useful review of appropriate study design, analysis, and interpretation of human GWA studies. CASPubMed Google Scholar
Feuk, L., Carson, A. R. & Scherer, S. W. Structural variation in the human genome. Nature Rev. Genet.7, 85–97 (2006). CASPubMed Google Scholar
Conrad, D. F. & Hurles, M. E. The population genetics of structural variation. Nature Genet.39, S30–S36 (2007). CASPubMed Google Scholar
Altshuler, D., Daly, M. J. & Lander, E. S. Genetic mapping in human disease. Science322, 881–888 (2008). A good recent review of the results of human GWA studies. Interestingly, the authors compare sample size requirements for genetic association studies of common and rare variants. CASPubMedPubMed Central Google Scholar
Donnelly, P. Progress and challenges in genome-wide association studies in humans. Nature456, 728–731 (2008). CASPubMed Google Scholar
Kruglyak, L. The road to genome-wide association studies. Nature Rev. Genet.9, 314–318 (2008). CASPubMed Google Scholar
Kimura, M. Evolutionary rate at the molecular level. Nature217, 624–626 (1968). CASPubMed Google Scholar
Ohta, T. Near-neutrality in evolution of genes and gene regulation. Proc. Natl Acad. Sci. USA99, 16134–16137 (2002). CASPubMedPubMed Central Google Scholar
Kruglyak, L. & Nickerson, D. A. Variation is the spice of life. Nature Genet.27, 234–236 (2001). CASPubMed Google Scholar
Slatkin, M. Linkage disequilibrium — understanding the evolutionary past and mapping the medical future. Nature Rev. Genet.9, 477–485 (2008). CASPubMed Google Scholar
Barrett, J. C. & Cardon, L. R. Evaluating coverage of genome-wide association studies. Nature Genet.38, 659–662 (2006). CASPubMed Google Scholar
Eberle, M. A. et al. Power to detect risk alleles using genome-wide tag SNP panels. PLoS Genet.3, e170 (2007). PubMed Central Google Scholar
Pe'er, I. et al. Evaluating and improving power in whole-genome association studies using fixed marker sets. Nature Genet.38, 663–667 (2006). CASPubMed Google Scholar
Clark, A. G. & Li, J. Conjuring SNPs to detect associations. Nature Genet.39, 815–816 (2007). CASPubMed Google Scholar
Tuzun, E. et al. Fine-scale structural variation of the human genome. Nature Genet.37, 727–732 (2005). CASPubMed Google Scholar
Cooper, G. M., Zerr, T., Kidd, J. M., Eichler, E. E. & Nickerson, D. A. Systematic assessment of copy number variant detection via genome-wide SNP genotyping. Nature Genet.40, 1199–1203 (2008). CASPubMed Google Scholar
Korbel, J. O. & al, e. Paired-end mapping reveals extensive structural variation in the human genome. Science318, 420–426 (2007). CASPubMedPubMed Central Google Scholar
Khaja, R. et al. Genome assembly comparison identifies structural variants in the human genome. Nature Genet.38, 1413–1418 (2006). CASPubMed Google Scholar
Conrad, D. F., Andrews, T. D., Carter, N. P., Hurles, M. E. & Pritchard, J. K. A high-resolution survey of deletion polymorphism in the human genome. Nature Genet.38, 75–81 (2006). CASPubMed Google Scholar
Barnes, C. et al. A robust statistical method for case-control association testing with copy number variation. Nature Genet.40, 1245–1252 (2008). CASPubMed Google Scholar
McCarroll, S. A. & Altshuler, D. M. Copy-number variation and association studies of human disease. Nature Genet.39, S37–S42 (2007). CASPubMed Google Scholar
Sebat, J. Major changes in our DNA lead to major changes in our thinking. Nature Genet.39, S3–S5 (2007). CASPubMed Google Scholar
Korn, J. M. et al. Integrated genotype calling and association analysis of SNPs, common copy number polymorphisms and rare CNVs. Nature Genet.40, 1253–1260 (2008). CASPubMed Google Scholar
Cooper, G. M., Nickerson, D. A. & Eichler, E. E. Mutational and selective effects on copy-number variants in the human genome. Nature Genet.39, S22–S29 (2007). CASPubMed Google Scholar
Hinds, D. A., Kloek, A. P., Jen, M., Chen, X. & Frazer, K. A. Common deletions and SNPs are in linkage disequilibrium in the human genome. Nature Genet.38, 9–11 (2006). Google Scholar
McCarroll, S. A. et al. Common deletion polymorphisms in the human genome. Nature Genet.38, 86–92 (2006). CASPubMed Google Scholar
McCarroll, S. A. et al. Integrated detection and population-genetic analysis of SNPs and copy number variation. Nature Genet.40, 1166–1174 (2008). Demonstrates that common structural variants are in LD with common SNPs in the human genome. CASPubMed Google Scholar
Jakobsson, M. et al. Genotype, haplotype and copy-number variation in worldwide human populations. Nature451, 998–1003 (2008). CASPubMed Google Scholar
Bailey, J. A. et al. Recent segmental duplications in the human genome. Science297, 1003–1007 (2002). CASPubMed Google Scholar
Locke, D. P. et al. Linkage disequilibrium and heritability of copy-number polymorphisms within duplicated regions of the human genome. Am. J. Hum. Genet.79, 275–290 (2006). CASPubMedPubMed Central Google Scholar
Pritchard, J. K. & Cox, N. J. The allelic architecture of human disease genes: common disease–common variant or not? Hum. Mol. Genet.11, 2417–2423 (2002). CASPubMed Google Scholar
Pritchard, J. K. Are rare variants responsible for susceptibility to complex diseases? Am. J. Hum. Genet.69, 124–137 (2001). CASPubMedPubMed Central Google Scholar
Reich, D. E. & Lander, E. S. On the allelic spectrum of human disease. Trends Genet.17, 502–510 (2001). CASPubMed Google Scholar
Lander, E. S. The new genomics: global views of biology. Science274, 536–539 (1996). CASPubMed Google Scholar
Chakravarti, A. Population genetics — making sense out of sequence. Nature Genet.21, 56–60 (1999). CASPubMed Google Scholar
Fearnhead, N. S., Winney, B. & Bodmer, W. F. Rare variant hypothesis for multifactorial inheritance: susceptibility to colorectal adenomas as a model. Cell Cycle4, 521–525 (2005). CASPubMed Google Scholar
Bodmer, W. & Bonilla, C. Common and rare variants in multifactorial susceptibility to common diseases. Nature Genet.40, 695–701 (2008). The authors discuss the concepts behind the common disease common–variant hypothesis and contrast them to the basic ideas that underlie the rare variant hypothesis. CASPubMed Google Scholar
Pearson, T. A. & Manolio, T. A. How to interpret a genome-wide association study. JAMA299, 1335–1344 (2008). CASPubMed Google Scholar
Iles, M. M. What can genome-wide association studies tell us about the genetics of common disease? PLoS Genet.4, e33 (2008). PubMedPubMed Central Google Scholar
Altshuler, D. & Daly, M. J. Guilt beyond a reasonable doubt. Nature Genet.39, 813–815 (2007). CASPubMed Google Scholar
Hindorff, L. A., Junkins, H. A., Mehta, J. P. and Manolio, T. A. A Catalog of Published Genome-Wide Association Studies. National Human Genome Research Institute [online], (accessed 1 Jan 2009). Google Scholar
Xavier, R. J. & Rioux, J. D. Genome-wide association studies: a new window into immune-mediated diseases. Nature Rev. Immunol.8, 631–643 (2008). CAS Google Scholar
Frayling, T. M. Genome-wide association studies provide new insights into type 2 diabetes aetiology. Nature Rev. Genet.8, 657–662 (2007). CASPubMed Google Scholar
Lyssenko, V. et al. Common variant in MTNR1B associated with increased risk of type 2 diabetes and impaired early insulin secretion. Nature Genet.41, 82–88 (2009). CASPubMed Google Scholar
Bouatia-Naji, N. et al. A variant near MTNR1B is associated with increased fasting plasma glucose levels and type 2 diabetes risk. Nature Genet.41, 89–94 (2009). CASPubMed Google Scholar
Aulchenko, Y. S. et al. Genetic variation in the KIF1B locus influences susceptibility to multiple sclerosis. Nature Genet.40, 1402–1403 (2008). CASPubMed Google Scholar
Hafler, D. A. et al. Risk alleles for multiple sclerosis identified by a genomewide study. N. Engl. J. Med.357, 851–862 (2007). CASPubMed Google Scholar
Lettre, G. & Rioux, J. D. Autoimmune diseases: insights from genome-wide association studies. Hum. Mol. Genet.17, R116–R121 (2008). CASPubMedPubMed Central Google Scholar
McPherson, R. et al. A common allele on chromosome 9 associated with coronary heart disease. Science316, 1488–1491 (2007). CASPubMedPubMed Central Google Scholar
Samani, N. J. et al. Genomewide association analysis of coronary artery disease. N. Engl. J. Med.357, 443–453 (2007). CASPubMedPubMed Central Google Scholar
Helgadottir, A. et al. A common variant on chromosome 9p21 affects the risk of myocardial infarction. Science316, 1491–1493 (2007). CASPubMed Google Scholar
Helgadottir, A. et al. The same sequence variant on 9p21 associates with myocardial infarction, abdominal aortic aneurysm and intracranial aneurysm. Nature Genet.40, 217–224 (2008). CASPubMed Google Scholar
Amundadottir, L. T. et al. A common variant associated with prostate cancer in European and African populations. Nature Genet.38, 652–658 (2006). CASPubMed Google Scholar
Freedman, M. L. et al. Admixture mapping identifies 8q24 as a prostate cancer risk locus in African-American men. Proc. Natl Acad. Sci. USA103, 14068–14073 (2006). CASPubMedPubMed Central Google Scholar
Cookson, W. et al. Mapping complex disease traits with global gene expression. Nature Rev. Genet.10, 184–194 (2009). CASPubMed Google Scholar
Myles, S., Davison, D., Barrett, J., Stoneking, M. & Timpson, N. Worldwide population differentiation at disease-associated SNPs. BMC Med. Genomics1, 22 (2008). PubMedPubMed Central Google Scholar
Sladek, R. et al. A genome-wide association study identifies novel risk loci for type 2 diabetes. Nature445, 881–885 (2007). CASPubMed Google Scholar
Saxena, R. et al. Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels. Science316, 1331–1336 (2007). CASPubMed Google Scholar
Scott, L. J. et al. A genome-wide association study of type 2 diabetes in Finns detects multiple susceptibility variants. Science316, 1341–1345 (2007). CASPubMedPubMed Central Google Scholar
Zeggini, E. et al. Replication of genome-wide association signals in UK samples reveals risk loci for type 2 diabetes. Science316, 1336–1341 (2007). CASPubMedPubMed Central Google Scholar
Xing, J. et al. HapMap tagSNP transferability in multiple populations: general guidelines. Genomics92, 41–51 (2008). CASPubMed Google Scholar
Chanock, S. J. et al. Replicating genotype–phenotype associations. Nature447, 655–660 (2007). CASPubMed Google Scholar
Weiss, L. A. et al. Association between microdeletion and microduplication at 16p11.2 and autism. N. Engl. J. Med.358, 667–675 (2008). CASPubMed Google Scholar
Kumar, R. A. et al. Recurrent 16p11.2 microdeletions in autism. Hum. Mol. Genet.17, 628–638 (2008). CASPubMed Google Scholar
Marshall, C. R. et al. Structural variation of chromosomes in autism spectrum disorder. Am. J. Hum. Genet.82, 477–488 (2008). CASPubMedPubMed Central Google Scholar
Consortium, I. S. Rare chromosomal deletions and duplications increase risk of schizophrenia. Nature455, 237–241 (2008). Google Scholar
Walsh, T. et al. Rare structural variants disrupt multiple genes in neurodevelopmental pathways in schizophrenia. Science320, 539–543 (2008). CASPubMed Google Scholar
Richards, J. B. et al. Male-pattern baldness susceptibility locus at 20p11. Nature Genet.40, 1282–1284 (2008). CASPubMed Google Scholar
Link, E. et al. SLCO1B1 variants and statin-induced myopathy — a genomewide study. N. Engl. J. Med.359, 789–799 (2008). CASPubMed Google Scholar
Graham, R. R. et al. Genetic variants near TNFAIP3 on 6q23 are associated with systemic lupus erythematosus. Nature Genet.40, 1059–1061 (2008). CASPubMed Google Scholar
Barrett, J. C. et al. Genome-wide association defines more than 30 distinct susceptibility loci for Crohn's disease. Nature Genet.40, 955–962 (2008). One of the human traits for which a large number of loci has been identified; the majority have modest effect sizes and in sum explain only a minority of the overall heritability. CASPubMed Google Scholar
Sulem, P. et al. Two newly identified genetic determinants of pigmentation in Europeans. Nature Genet.40, 835–837 (2008). CASPubMed Google Scholar
Sulem, P. et al. Genetic determinants of hair, eye and skin pigmentation in Europeans. Nature Genet.39, 1443–1452 (2007). CASPubMed Google Scholar
Stokowski, R. P. et al. A genomewide association study of skin pigmentation in a South Asian population. Am. J. Hum. Genet.81, 1119–1132 (2007). CASPubMedPubMed Central Google Scholar
Buch, S. et al. A genome-wide association scan identifies the hepatic cholesterol transporter ABCG8 as a susceptibility factor for human gallstone disease. Nature Genet.39, 995–999 (2007). CASPubMed Google Scholar
Klein, R. J. et al. Complement factor H polymorphism in age-related macular degeneration. Science308, 385–389 (2005). CASPubMedPubMed Central Google Scholar
Thorleifsson, G. et al. Common sequence variants in the LOXL1 gene confer susceptibility to exfoliation glaucoma. Science317, 1397–1400 (2007). CASPubMed Google Scholar
Weedon, M. N. et al. A common variant of HMGA2 is associated with adult and childhood height in the general population. Nature Genet.39, 1245–1250 (2007). CASPubMed Google Scholar
Sanna, S. et al. Common variants in the GDF5-UQCC region are associated with variation in human height. Nature Genet.40, 198–203 (2008). CASPubMed Google Scholar
Weedon, M. N. et al. Genome-wide association analysis identifies 20 loci that influence adult height. Nature Genet.40, 575–583 (2008). CASPubMed Google Scholar
Lettre, G. et al. Identification of ten loci associated with height highlights new biological pathways in human growth. Nature Genet.40, 584–591 (2008). CASPubMed Google Scholar
Gudbjartsson, D. F. et al. Many sequence variants affecting diversity of adult human height. Nature Genet.40, 609–615 (2008). CASPubMed Google Scholar
Weedon, M. N. & Frayling, T. M. Reaching new heights: insights into the genetics of human stature. Trends Genet.24, 595–603 (2008). CASPubMed Google Scholar
Aulchenko, Y. S. et al. Loci influencing lipid levels and coronary heart disease risk in 16 European population cohorts. Nature Genet.41, 47–55 (2008). PubMed Google Scholar
Willer, C. J. et al. Newly identified loci that influence lipid concentrations and risk of coronary artery disease. Nature Genet.40, 161–169 (2008). CASPubMed Google Scholar
Kathiresan, S. et al. Common variants at 30 loci contribute to polygenic dyslipidemia. Nature Genet.41, 56–65 (2009). CASPubMed Google Scholar
Fearnhead, N. S. et al. Multiple rare variants in different genes account for multifactorial inherited susceptibility to colorectal adenomas. Proc. Natl Acad. Sci. USA101, 15992–15997 (2004). CASPubMedPubMed Central Google Scholar
Cohen, J. C. et al. Multiple rare alleles contribute to low plasma levels of HDL cholesterol. Science305, 869–872 (2004). One of the first studies to demonstrate that multiple rare alleles with high penetrance collectively contribute to a common phenotype in the general population. CASPubMed Google Scholar
Kotowski, I. K. et al. A spectrum of PCSK9 alleles contributes to plasma levels of low-density lipoprotein cholesterol. Am. J. Hum. Genet.78, 410–422 (2006). CASPubMedPubMed Central Google Scholar
Romeo, S. et al. Population-based resequencing of ANGPTL4 uncovers variations that reduce triglycerides and increase HDL. Nature Genet.39, 513–516 (2007). CASPubMed Google Scholar
Marini, N. J. et al. The prevalence of folate-remedial MTHFR enzyme variants in humans. Proc. Natl Acad. Sci. USA105, 8055–8060 (2008). CASPubMedPubMed Central Google Scholar
Birney, E. et al. Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project. Nature447, 799–816 (2007). The goal of this project was to develop efficient methods for functionally annotating human genomic sequences. The work yielded new understandings of transcription regulatory sequences and their relationships with features of chromatin accessibility and histone modification. CASPubMed Google Scholar
Wade, C. M. & Daly, M. J. Genetic variation in laboratory mice. Nature Genet.37, 1175–1180 (2005). CASPubMed Google Scholar
Erickson, R. P. Mouse models of human genetic disease: which mouse is more like a man? Bioessays18, 993–998 (1996). CASPubMed Google Scholar
Linder, C. C. The influence of genetic background on spontaneous and genetically engineered mouse models of complex diseases. Lab. Anim. (NY)30, 34–39 (2001). CAS Google Scholar
Frankel, W. N. Taking stock of complex trait genetics in mice. Trends Genet.11, 471–477 (1995). CASPubMed Google Scholar
Shao, H. et al. Genetic architecture of complex traits: large phenotypic effects and pervasive epistasis. Proc. Natl Acad. Sci. USA105, 19910–19914 (2008). CASPubMedPubMed Central Google Scholar
Maller, J. et al. Common variation in three genes, including a noncoding variant in CFH, strongly influences risk of age-related macular degeneration. Nature Genet.38, 1055–1059 (2006). CASPubMed Google Scholar
Li, M. et al. CFH haplotypes without the Y402H coding variant show strong association with susceptibility to age-related macular degeneration. Nature Genet.38, 1049–1054 (2006). CASPubMed Google Scholar
Rioux, J. D. et al. Genome-wide association study identifies new susceptibility loci for Crohn disease and implicates autophagy in disease pathogenesis. Nature Genet.39, 596–604 (2007). CASPubMed Google Scholar
Carlson, C. S. et al. Selecting a maximally informative set of single-nucleotide polymorphisms for association analyses using linkage disequilibrium. Am. J. Hum. Genet.74, 106–120 (2004). CASPubMed Google Scholar
Pollin, T. I. et al. A null mutation in human APOC3 confers a favorable plasma lipid profile and apparent cardioprotection. Science322, 1702–1705 (2008). CASPubMedPubMed Central Google Scholar
Sabatti, C. et al. Genome-wide association analysis of metabolic traits in a birth cohort from a founder population. Nature Genet.41, 35–46 (2008). PubMed Google Scholar
Scherer, S. W. et al. Challenges and standards in integrating surveys of structural variation. Nature Genet.39, S7–S15 (2007). CASPubMed Google Scholar
Stefansson, H. et al. A common inversion under selection in Europeans. Nature Genet.37, 129–137 (2005). CASPubMed Google Scholar
Zeggini, E. et al. Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes. Nature Genet.40, 638–645 (2008). CASPubMed Google Scholar
Steinthorsdottir, V. et al. A variant in CDKAL1 influences insulin response and risk of type 2 diabetes. Nature Genet.39, 770–775 (2007). CASPubMed Google Scholar
Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature447, 661–678 (2007).
Frayling, T. M. et al. A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity. Science316, 889–894 (2007). CASPubMedPubMed Central Google Scholar
Gerken, T. et al. The obesity-associated FTO gene encodes a 2-oxoglutarate-dependent nucleic acid demethylase. Science318, 1469–1472 (2007). CASPubMedPubMed Central Google Scholar
Prokopenko, I. et al. Variants in MTNR1B influence fasting glucose levels. Nature Genet.41, 77–81 (2009). CASPubMed Google Scholar
Bayat, A., Barton, A. & Ollier, W. E. Dissection of complex genetic disease: implications for orthopaedics. Clin. Orthop. Relat. Res.419, 297–305 (2004). Google Scholar
Vang, T. et al. Autoimmune-associated lymphoid tyrosine phosphatase is a gain-of-function variant. Nature Genet.37, 1317–1319 (2005). CASPubMed Google Scholar
Gudmundsson, J. et al. Two variants on chromosome 17 confer prostate cancer risk, and the one in TCF2 protects against type 2 diabetes. Nature Genet.39, 977–983 (2007). CASPubMed Google Scholar
Thomas, G. et al. Multiple loci identified in a genome-wide association study of prostate cancer. Nature Genet.40, 310–315 (2008). CASPubMed Google Scholar