Sivakumaran, S. et al. Abundant pleiotropy in human complex diseases and traits. Am. J. Hum. Genet. 89, 607–618 (2011).
Cotsapas, C. et al. Pervasive sharing of genetic effects in autoimmune disease. PLoS Genet. 7, e1002254 (2011).
Cross-Disorder Group of the Psychiatric Genomics Consortium. Identification of risk loci with shared effects on five major psychiatric disorders: a genome-wide analysis. Lancet 381, 1371–1379 (2013).
Fortune, M.D. et al. Statistical colocalization of genetic risk variants for related autoimmune diseases in the context of common controls. Nat. Genet. 47, 839–846 (2015).
Lee, S.H., Yang, J., Goddard, M.E., Visscher, P.M. & Wray, N.R. Estimation of pleiotropy between complex diseases using single-nucleotide polymorphism–derived genomic relationships and restricted maximum likelihood. Bioinformatics 28, 2540–2542 (2012).
Cross-Disorder Group of the Psychiatric Genomics Consortium. Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs. Nat. Genet. 45, 984–994 (2013).
Bulik-Sullivan, B. et al. An atlas of genetic correlations across human diseases and traits. Nat. Genet. 47, 1236–1241 (2015).
Pendergrass, S.A. et al. Phenome-wide association study (PheWAS) for detection of pleiotropy within the Population Architecture using Genomics and Epidemiology (PAGE) Network. PLoS Genet. 9, e1003087 (2013).
Collins, F.S. & Varmus, H. A new initiative on precision medicine. N. Engl. J. Med. 372, 793–795 (2015).
Criswell, L.A. et al. Analysis of families in the Multiple Autoimmune Disease Genetics Consortium (MADGC) collection: the PTPN22 620W allele associates with multiple autoimmune phenotypes. Am. J. Hum. Genet. 76, 561–571 (2005).
Kendler, K.S., Neale, M.C., Kessler, R.C., Heath, A.C. & Eaves, L.J. Major depression and generalized anxiety disorder. Same genes, (partly) different environments? Arch. Gen. Psychiatry 49, 716–722 (1992).
Wray, N.R., Goddard, M.E. & Visscher, P.M. Prediction of individual genetic risk to disease from genome-wide association studies. Genome Res. 17, 1520–1528 (2007).
International Schizophrenia Consortium. Common polygenic variation contributes to risk of schizophrenia and bipolar disorder. Nature 460, 748–752 (2009).
Lee, S.H. et al. New data and an old puzzle: the negative association between schizophrenia and rheumatoid arthritis. Int. J. Epidemiol. 44, 1706–1721 (2015).
Power, R.A. et al. Polygenic risk scores for schizophrenia and bipolar disorder predict creativity. Nat. Neurosci. 18, 953–955 (2015).
Solovieff, N., Cotsapas, C., Lee, P.H., Purcell, S.M. & Smoller, J.W. Pleiotropy in complex traits: challenges and strategies. Nat. Rev. Genet. 14, 483–495 (2013).
Wray, N.R., Lee, S.H. & Kendler, K.S. Impact of diagnostic misclassification on estimation of genetic correlations using genome-wide genotypes. Eur. J. Hum. Genet. 20, 668–674 (2012).
Silverberg, M.S. et al. Diagnostic misclassification reduces the ability to detect linkage in inflammatory bowel disease genetic studies. Gut 49, 773–776 (2001).
van der Linden, M.P. et al. Value of anti–modified citrullinated vimentin and third-generation anti–cyclic citrullinated peptide compared with second-generation anti–cyclic citrullinated peptide and rheumatoid factor in predicting disease outcome in undifferentiated arthritis and rheumatoid arthritis. Arthritis Rheum. 60, 2232–2241 (2009).
Wiik, A.S., van Venrooij, W.J. & Pruijn, G.J. All you wanted to know about anti-CCP but were afraid to ask. Autoimmun. Rev. 10, 90–93 (2010).
Bromet, E.J. et al. Diagnostic shifts during the decade following first admission for psychosis. Am. J. Psychiatry 168, 1186–1194 (2011).
Gibson, P. et al. Subtypes of medulloblastoma have distinct developmental origins. Nature 468, 1095–1099 (2010).
Smoller, J.W., Lunetta, K.L. & Robins, J. Implications of comorbidity and ascertainment bias for identifying disease genes. Am. J. Med. Genet. 96, 817–822 (2000).
Burrell, R.A., McGranahan, N., Bartek, J. & Swanton, C. The causes and consequences of genetic heterogeneity in cancer evolution. Nature 501, 338–345 (2013).
Jeste, S.S. & Geschwind, D.H. Disentangling the heterogeneity of autism spectrum disorder through genetic findings. Nat. Rev. Neurol. 10, 74–81 (2014).
Flint, J. & Kendler, K.S. The genetics of major depression. Neuron 81, 484–503 (2014).
Cho, J.H. & Feldman, M. Heterogeneity of autoimmune diseases: pathophysiologic insights from genetics and implications for new therapies. Nat. Med. 21, 730–738 (2015).
Welter, D. et al. The NHGRI GWAS Catalog, a curated resource of SNP–trait associations. Nucleic Acids Res. 42, D1001–D1006 (2014).
Raychaudhuri, S. et al. Genetic variants at CD28, PRDM1 and CD2/CD58 are associated with rheumatoid arthritis risk. Nat. Genet. 41, 1313–1318 (2009).
Eyre, S. et al. High-density genetic mapping identifies new susceptibility loci for rheumatoid arthritis. Nat. Genet. 44, 1336–1340 (2012).
International HapMap Consortium. The International HapMap Project. Nature 426, 789–796 (2003).
Smyth, D.J. et al. Shared and distinct genetic variants in type 1 diabetes and celiac disease. N. Engl. J. Med. 359, 2767–2777 (2008).
Festen, E.A. et al. A meta-analysis of genome-wide association scans identifies IL18RAP, PTPN2, TAGAP, and PUS10 as shared risk loci for Crohn's disease and celiac disease. PLoS Genet. 7, e1001283 (2011).
Zhernakova, A. et al. Meta-analysis of genome-wide association studies in celiac disease and rheumatoid arthritis identifies fourteen non-HLA shared loci. PLoS Genet. 7, e1002004 (2011).
Jostins, L. et al. Host–microbe interactions have shaped the genetic architecture of inflammatory bowel disease. Nature 491, 119–124 (2012).
Cotsapas, C. & Hafler, D.A. Immune-mediated disease genetics: the shared basis of pathogenesis. Trends Immunol. 34, 22–26 (2013).
Onengut-Gumuscu, S. et al. Fine mapping of type 1 diabetes susceptibility loci and evidence for colocalization of causal variants with lymphoid gene enhancers. Nat. Genet. 47, 381–386 (2015).
Han, B. et al. Fine mapping seronegative and seropositive rheumatoid arthritis to shared and distinct HLA alleles by adjusting for the effects of heterogeneity. Am. J. Hum. Genet. 94, 522–532 (2014).
Schizophrenia Working Group of the Psychiatric Genomics Consortium. Biological insights from 108 schizophrenia-associated genetic loci. Nature 511, 421–427 (2014).
Ripke, S. et al. A mega-analysis of genome-wide association studies for major depressive disorder. Mol. Psychiatry 18, 497–511 (2013).
Wray, N.R. & Maier, R. Genetic basis of complex genetic disease: the contribution of disease heterogeneity to missing heritability. Curr. Epidemiol. Rep. 1, 220–227 (2014).
Jennrich, R.I. An asymptotic χ2 test for the equality of two correlation matrices. J. Am. Stat. Assoc. 65, 904–912 (1970).
Wei, L.J., Lin, D.Y. & Weissfeld, L. Regression analysis of multivariate incomplete failure time data by modeling marginal distributions. J. Am. Stat. Assoc. 84, 1065–1073 (1989).
Lin, D.Y. & Sullivan, P.F. Meta-analysis of genome-wide association studies with overlapping subjects. Am. J. Hum. Genet. 85, 862–872 (2009).
Purcell, S. et al. PLINK: a tool set for whole-genome association and population-based linkage analyses. Am. J. Hum. Genet. 81, 559–575 (2007).