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Nat Rev Genet DOI:10.1038/nrg3461

Pleiotropy in complex traits: challenges and strategies.

Publication TypeJournal Article
Year of Publication2013
AuthorsSolovieff, N, Cotsapas, C, Lee, PH, Purcell, SM, Smoller, JW
JournalNat Rev Genet
Date Published2013 Jul
KeywordsAlleles, Chromosome Mapping, Genetic Diseases, Inborn, Genetic Predisposition to Disease, Genetic Variation, Genome-Wide Association Study, Genotype, Humans, Models, Genetic, Multivariate Analysis, Phenotype

Genome-wide association studies have identified many variants that each affects multiple traits, particularly across autoimmune diseases, cancers and neuropsychiatric disorders, suggesting that pleiotropic effects on human complex traits may be widespread. However, systematic detection of such effects is challenging and requires new methodologies and frameworks for interpreting cross-phenotype results. In this Review, we discuss the evidence for pleiotropy in contemporary genetic mapping studies, new and established analytical approaches to identifying pleiotropic effects, sources of spurious cross-phenotype effects and study design considerations. We also outline the molecular and clinical implications of such findings and discuss future directions of research.


Alternate JournalNat. Rev. Genet.
PubMed ID23752797
PubMed Central IDPMC4104202
Grant ListK24 MH094614 / MH / NIMH NIH HHS / United States
R01 MH079799 / MH / NIMH NIH HHS / United States
K24MH094614 / MH / NIMH NIH HHS / United States
R01‑MH079799 / MH / NIMH NIH HHS / United States