Backman, J. D. et al. Exome sequencing and analysis of 454,787 UK Biobank participants. Nature 599, 628–634 (2021).
Article CAS PubMed PubMed Central Google Scholar
Gaziano, J. M. et al. Million veteran program: a mega-biobank to study genetic influences on health and disease. J. Clin. Epidemiol. 70, 214–223 (2016).
Denny, J. C. et al. The “All of Us” research program. N. Engl. J. Med. 381, 668–676 (2019).
Consortium, I. M. S. G. Low-frequency and rare-coding variation contributes to multiple sclerosis risk. Cell 175, 1679–1687.e1677 (2018).
Marouli, E. et al. Rare and low-frequency coding variants alter human adult height. Nature 542, 186–190 (2017).
Article CAS PubMed PubMed Central Google Scholar
Lee, A. et al. BOADICEA: a comprehensive breast cancer risk prediction model incorporating genetic and nongenetic risk factors. Genet. Med. 21, 1708–1718 (2019).
Article PubMed PubMed Central Google Scholar
Curtis, D. Construction of an exome-wide risk score for schizophrenia based on a weighted burden test. Ann. Hum. Genet. 82, 11–22 (2018).
Article CAS PubMed Google Scholar
Biddinger, K. J. et al. Rare and common genetic variation underlying the risk of hypertrophic cardiomyopathy in a national biobank. JAMA Cardiol. 7, 715–722 (2022).
Article PubMed PubMed Central Google Scholar
Wright, C. F. et al. Genomic diagnosis of rare pediatric disease in the United Kingdom and Ireland. N. Engl. J. Med. 388, 1559–1571 (2023).
Article CAS PubMed PubMed Central Google Scholar
Lunke, S. et al. Integrated multi-omics for rapid rare disease diagnosis on a national scale. Nat. Med. 29, 1681–1691 (2023).
Article CAS PubMed PubMed Central Google Scholar
Beck, D. B. et al. Somatic mutations in UBA1 and severe adult-onset autoinflammatory disease. N. Engl. J. Med. 383, 2628–2638 (2020).
Article CAS PubMed PubMed Central Google Scholar
Cohen, J. C., Boerwinkle, E., Mosley, T. H. Jr & Hobbs, H. H. Sequence variations in PCSK9, low LDL, and protection against coronary heart disease. N. Engl. J. Med. 354, 1264–1272 (2006).
Article CAS PubMed Google Scholar
Whiffin, N. et al. The effect of LRRK2 loss-of-function variants in humans. Nat. Med. 26, 869–877 (2020).
Article CAS PubMed PubMed Central Google Scholar
Akbari, P. et al. Sequencing of 640,000 exomes identifies GPR75 variants associated with protection from obesity. Science 373, eabf8683 (2021).
Article CAS PubMed PubMed Central Google Scholar
Nelson, M. R. et al. The support of human genetic evidence for approved drug indications. Nat. Genet. 47, 856–860 (2015).
Article CAS PubMed Google Scholar
Myasoedova, E., Davis, J., Matteson, E. L. & Crowson, C. S. Is the epidemiology of rheumatoid arthritis changing? Results from a population-based incidence study, 1985-2014. Ann. Rheum. Dis. 79, 440–444 (2020).
Frisell, T. et al. Familial risks and heritability of rheumatoid arthritis: role of rheumatoid factor/anti-citrullinated protein antibody status, number and type of affected relatives, sex, and age. Arthritis Rheum. 65, 2773–2782 (2013).
Article CAS PubMed Google Scholar
Svendsen, A. J. et al. On the origin of rheumatoid arthritis: the impact of environment and genes — a population based twin study. PLoS One 8, e57304 (2013).
Article CAS PubMed PubMed Central Google Scholar
Stastny, P. Mixed lymphocyte cultures in rheumatoid arthritis. J. Clin. Invest. 57, 1148–1157 (1976).
Article CAS PubMed PubMed Central Google Scholar
Gough, S. C. & Simmonds, M. J. The HLA region and autoimmune disease: associations and mechanisms of action. Curr. Genomics 8, 453–465 (2007).
Article CAS PubMed PubMed Central Google Scholar
Kulski, J. K., Suzuki, S. & Shiina, T. Human leukocyte antigen super-locus: nexus of genomic supergenes, SNPs, indels, transcripts, and haplotypes. Hum. Genome Var. 9, 49 (2022).
Article CAS PubMed PubMed Central Google Scholar
Gregersen, P. K., Silver, J. & Winchester, R. J. The shared epitope hypothesis. An approach to understanding the molecular genetics of susceptibility to rheumatoid arthritis. Arthritis Rheum. 30, 1205–1213 (1987).
Article CAS PubMed Google Scholar
Raychaudhuri, S. et al. Five amino acids in three HLA proteins explain most of the association between MHC and seropositive rheumatoid arthritis. Nat. Genet. 44, 291–296 (2012).
Article CAS PubMed PubMed Central Google Scholar
Begovich, A. B. et al. A missense single-nucleotide polymorphism in a gene encoding a protein tyrosine phosphatase (PTPN22) is associated with rheumatoid arthritis. Am. J. Hum. Genet. 75, 330–337 (2004).
Article CAS PubMed PubMed Central Google Scholar
Rieck, M. et al. Genetic variation in PTPN22 corresponds to altered function of T and B lymphocytes. J. Immunol. 179, 4704–4710 (2007).
Article CAS PubMed Google Scholar
Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature 447, 661-678 (2007).
Ishigaki, K. et al. Multi-ancestry genome-wide association analyses identify novel genetic mechanisms in rheumatoid arthritis. Nat. Genet. 54, 1640–1651 (2022).
Article CAS PubMed PubMed Central Google Scholar
Sparks, J. A. et al. Improved performance of epidemiologic and genetic risk models for rheumatoid arthritis serologic phenotypes using family history. Ann. Rheum. Dis. 74, 1522–1529 (2015).
Rostami, S., Hoff, M., Brown, M. A., Hveem, K. & Videm, V. Comparison of methods to construct a genetic risk score for prediction of rheumatoid arthritis in the population-based Nord-Trondelag Health Study, Norway. Rheumatology 59, 1743–1751 (2020).
Article CAS PubMed Google Scholar
Manolio, T. A. et al. Finding the missing heritability of complex diseases. Nature 461, 747–753 (2009).
Article CAS PubMed PubMed Central Google Scholar
Stahl, E. A. et al. Bayesian inference analyses of the polygenic architecture of rheumatoid arthritis. Nat. Genet. 44, 483–489 (2012).
Article CAS PubMed PubMed Central Google Scholar
Rapaport, F. et al. Negative selection on human genes underlying inborn errors depends on disease outcome and both the mode and mechanism of inheritance. Proc. Natl Acad. Sci. USA 118, e2001248118 (2021).
Article CAS PubMed PubMed Central Google Scholar
Lee, S., Abecasis, G. R., Boehnke, M. & Lin, X. Rare-variant association analysis: study designs and statistical tests. Am. J. Hum. Genet. 95, 5–23 (2014).
Article CAS PubMed PubMed Central Google Scholar
Momozawa, Y. & Mizukami, K. Unique roles of rare variants in the genetics of complex diseases in humans. J. Hum. Genet. 66, 11–23 (2021).
Diogo, D. et al. TYK2 protein-coding variants protect against rheumatoid arthritis and autoimmunity, with no evidence of major pleiotropic effects on non-autoimmune complex traits. PLoS One 10, e0122271 (2015).
Article PubMed PubMed Central Google Scholar
National Human Genome Research Institute. Human Genomic Variation. https://www.genome.gov/about-genomics/educational-resources/fact-sheets/human-genomic-variation (2023).
Lee, S. et al. Optimal unified approach for rare-variant association testing with application to small-sample case-control whole-exome sequencing studies. Am. J. Hum. Genet. 91, 224–237 (2012).
Article CAS PubMed PubMed Central Google Scholar
Eichler, E. E. Genetic variation, comparative genomics, and the diagnosis of disease. N. Engl. J. Med. 381, 64–74 (2019).
Comments (0)