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Nat Rev Genet. 2013 Jul;14(7):483-95. doi: 10.1038/nrg3461. Epub 2013 Jun 11.

Pleiotropy in complex traits: challenges and strategies.

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  • 1Center for Human Genetics Research, Massachusetts General Hospital, 185 Cambridge Street, Boston, Massachusetts 02114, USA.

Abstract

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.

PMID:
23752797
[PubMed - indexed for MEDLINE]
PMCID:
PMC4104202
Free PMC Article

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