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PMID: 27346688 Published · ppublish English Journal Article

Contrasting the Genetic Architecture of 30 Complex Traits from Summary Association Data.

American journal of human genetics ·Vol. 99 ·No. 1 ·2016-00-07 ·Pages 139-53

Shi H, Kichaev G, Pasaniuc B

Abstract

Variance-component methods that estimate the aggregate contribution of large sets of variants to the heritability of complex traits have yielded important insights into the genetic architecture of common diseases. Here, we introduce methods that estimate the total trait variance explained by the typed variants at a single locus in the genome (local SNP heritability) from genome-wide association study (GWAS) summary data while accounting for linkage disequilibrium among variants. We applied our estimator to ultra-large-scale GWAS summary data of 30 common traits and diseases to gain insights into their local genetic architecture. First, we found that common SNPs have a high contribution to the heritability of all studied traits. Second, we identified traits for which the majority of the SNP heritability can be confined to a small percentage of the genome. Third, we identified GWAS risk loci where the entire locus explains significantly more variance in the trait than the GWAS reported variants. Finally, we identified loci that explain a significant amount of heritability across multiple traits.

MeSH Terms
Datasets as Topic Genetic Predisposition to Disease/genetics Genome-Wide Association Study Humans Linkage Disequilibrium/genetics Models, Genetic Multifactorial Inheritance/genetics Phenotype Polymorphism, Single Nucleotide/genetics Quantitative Trait Loci/genetics
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Shi Huwenbo
Bioinformatics Interdepartmental Program, University of California, Los Angeles, Los Angeles, CA 90024, USA.
Kichaev Gleb
Bioinformatics Interdepartmental Program, University of California, Los Angeles, Los Angeles, CA 90024, USA.
Pasaniuc Bogdan
Bioinformatics Interdepartmental Program, University of California, Los Angeles, Los Angeles, CA 90024, USA; Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90024, USA; Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90024, USA. Electronic address: [email protected].
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Article Info
Journal
American journal of human genetics
Abbr.
Am J Hum Genet
ISSN
1537-6605
DOI
10.1016/j.ajhg.2016.05.013
Email
[email protected]
Published
2016-00-07
Epub
2016-00-23
Pages
139-53
Language
English
Region
United States
NLM ID
0370475
PMCID
PMC5005444
Subset
IM
External Links
PubMed source DOI: 10.1016/j.ajhg.2016.05.013 PMC Full Text View journal details
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