Finding the missing heritability of complex diseases.


Journal Article (Review)

Genome-wide association studies have identified hundreds of genetic variants associated with complex human diseases and traits, and have provided valuable insights into their genetic architecture. Most variants identified so far confer relatively small increments in risk, and explain only a small proportion of familial clustering, leading many to question how the remaining, 'missing' heritability can be explained. Here we examine potential sources of missing heritability and propose research strategies, including and extending beyond current genome-wide association approaches, to illuminate the genetics of complex diseases and enhance its potential to enable effective disease prevention or treatment.

Full Text

Cited Authors

  • Manolio, TA; Collins, FS; Cox, NJ; Goldstein, DB; Hindorff, LA; Hunter, DJ; McCarthy, MI; Ramos, EM; Cardon, LR; Chakravarti, A; Cho, JH; Guttmacher, AE; Kong, A; Kruglyak, L; Mardis, E; Rotimi, CN; Slatkin, M; Valle, D; Whittemore, AS; Boehnke, M; Clark, AG; Eichler, EE; Gibson, G; Haines, JL; Mackay, TFC; McCarroll, SA; Visscher, PM

Published Date

  • October 2009

Published In

Volume / Issue

  • 461 / 7265

Start / End Page

  • 747 - 753

PubMed ID

  • 19812666

Pubmed Central ID

  • 19812666

Electronic International Standard Serial Number (EISSN)

  • 1476-4687

International Standard Serial Number (ISSN)

  • 0028-0836

Digital Object Identifier (DOI)

  • 10.1038/nature08494


  • eng