Finding the missing heritability of complex diseases.

Full Abstract

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.

Author information

Author/s: Manolio, Teri A (TA); Collins, Francis S (FS); Cox, Nancy J (NJ); Goldstein, David B (DB); Hindorff, Lucia A (LA); Hunter, David J (DJ); McCarthy, Mark I (MI); Ramos, Erin M (EM); Cardon, Lon R (LR); Chakravarti, Aravinda (A); Cho, Judy H (JH); Guttmacher, Alan E (AE); Kong, Augustine (A); Kruglyak, Leonid (L); Mardis, Elaine (E); Rotimi, Charles N (CN); Slatkin, Montgomery (M); Valle, David (D); Whittemore, Alice S (AS); Boehnke, Michael (M); Clark, Andrew G (AG); Eichler, Evan E (EE); Gibson, Greg (G); Haines, Jonathan L (JL); Mackay, Trudy F C (TF); McCarroll, Steven A (SA); Visscher, Peter M (PM);

Affiliation: National Human Genome Research Institute, Building 31, Room 4B09, 31 Center Drive, MSC 2152, Bethesda, Maryland 20892-2152, USA. manoliot(-atsign-)mail.nih.gov

Journal and publication information

Publication Type: Journal Article; Review

Journal: Nature (Nature), published in England. (Language: eng)

Reference: 2009-Oct; vol 461 (issue 7265) : pp 747-53

Dates: Created 2009/10/08; Completed 2009/10/20;

PMID: 19812666, status: MEDLINE (last retrieval date: 10/20/2009, IMS Date: )

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