PuSH - Publication Server of Helmholtz Zentrum München

Magosi, L.E.* ; Goel, A.* ; Hopewell, J.C.* ; Farrall, M.* ; CARDIoGRAMplusC4D Consortium (Gieger, C. ; Peters, A. ; Meitinger, T.)

Identifying systematic heterogeneity patterns in genetic association meta-analysis studies.

PLoS Genet. 13:e1006755 (2017)
Publ. Version/Full Text Research data DOI
Open Access Gold
Creative Commons Lizenzvertrag
Progress in mapping loci associated with common complex diseases or quantitative inherited traits has been expedited by large-scale meta-analyses combining information across multiple studies, assembled through collaborative networks of researchers. Participating studies will usually have been independently designed and implemented in unique settings that are potential sources of phenotype, ancestry or other variability that could introduce between-study heterogeneity into a meta-analysis. Heterogeneity tests based on individual genetic variants (e.g. Q, I-2) are not suited to identifying locus-specific from more systematic multi-locus or genome-wide patterns of heterogeneity. We have developed and evaluated an aggregate heterogeneity M statistic that combines between-study heterogeneity information across multiple genetic variants, to reveal systematic patterns of heterogeneity that elude conventional single variant analysis. Application to a GWAS meta-analysis of coronary disease with 48 contributing studies uncovered substantial systematic between-study heterogeneity, which could be partly explained by age-of-disease onset, family-history of disease and ancestry. Future meta-analyses of diseases and traits with multiple known genetic associations can use this approach to identify outlier studies and thereby optimize power to detect novel genetic associations.
Altmetric
Additional Metrics?
[➜Log in]
Edit extra informations Login
Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Genome-wide Association; Coronary-artery-disease; Meta-regression; China
ISSN (print) / ISBN 1553-7390
e-ISSN 1553-7404
Journal PLoS Genetics
Quellenangaben Volume: 13, Issue: 5, Pages: , Article Number: e1006755 Supplement: ,
Publisher Public Library of Science (PLoS)
Publishing Place San Francisco
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Epidemiology II (EPI2)
Institute of Human Genetics (IHG)
Institute of Genetic Epidemiology (IGE)