CHS Home | Welcome New Investigators | Directory | Contact Us

 

You are here

Home

Meta-analysis of gene-environment interaction: joint estimation of SNP and SNP × environment regression coefficients.

Tuesday,2012-11-06 12:25 America/Los_Angeles — eenright
TitleMeta-analysis of gene-environment interaction: joint estimation of SNP and SNP × environment regression coefficients.
Publication TypeJournal Article
Year of Publication2011
AuthorsManning, AK, LaValley, M, Liu, C-T, Rice, K, An, P, Liu, Y, Miljkovic, I, Rasmussen-Torvik, L, Harris, TB, Province, MA, Borecki, IB, Florez, JC, Meigs, JB, Cupples, AL, Dupuis, J
JournalGenet Epidemiol
Volume35
Issue1
Pagination11-8
Date Published2011 Jan
ISSN1098-2272
KeywordsAdult, Aged, Body Mass Index, Confidence Intervals, Diabetes Mellitus, Type 2, Environment, Fasting, Female, Genome, Human, Genome-Wide Association Study, Genotype, Humans, Insulin, Least-Squares Analysis, Male, Mathematical Computing, Meta-Analysis as Topic, Middle Aged, Polymorphism, Single Nucleotide, PPAR gamma
Abstract<p><b>INTRODUCTION: </b>Genetic discoveries are validated through the meta-analysis of genome-wide association scans in large international consortia. Because environmental variables may interact with genetic factors, investigation of differing genetic effects for distinct levels of an environmental exposure in these large consortia may yield additional susceptibility loci undetected by main effects analysis. We describe a method of joint meta-analysis (JMA) of SNP and SNP by Environment (SNP × E) regression coefficients for use in gene-environment interaction studies.</p><p><b>METHODS: </b>In testing SNP × E interactions, one approach uses a two degree of freedom test to identify genetic variants that influence the trait of interest. This approach detects both main and interaction effects between the trait and the SNP. We propose a method to jointly meta-analyze the SNP and SNP × E coefficients using multivariate generalized least squares. This approach provides confidence intervals of the two estimates, a joint significance test for SNP and SNP × E terms, and a test of homogeneity across samples.</p><p><b>RESULTS: </b>We present a simulation study comparing this method to four other methods of meta-analysis and demonstrate that the JMA performs better than the others when both main and interaction effects are present. Additionally, we implemented our methods in a meta-analysis of the association between SNPs from the type 2 diabetes-associated gene PPARG and log-transformed fasting insulin levels and interaction by body mass index in a combined sample of 19,466 individuals from five cohorts.</p>
DOI10.1002/gepi.20546
Alternate JournalGenet. Epidemiol.
PubMed ID21181894
PubMed Central IDPMC3312394
Grant ListN01HC55020 / HL / NHLBI NIH HHS / United States
R01 DK078616 / DK / NIDDK NIH HHS / United States
R01 DK078616-05 / DK / NIDDK NIH HHS / United States
N02-HL-6-4278 / HL / NHLBI NIH HHS / United States
N01-HC-25195 / HC / NHLBI NIH HHS / United States
5R01 HL08770003 / HL / NHLBI NIH HHS / United States
N1AG62101A / AG / NIA NIH HHS / United States
R01 HL088215-02 / HL / NHLBI NIH HHS / United States
R01 HL059367-11 / HL / NHLBI NIH HHS / United States
N01HC55018 / HL / NHLBI NIH HHS / United States
U01 HL080295-04 / HL / NHLBI NIH HHS / United States
R01HL59367 / HL / NHLBI NIH HHS / United States
R01 HL087652-03 / HL / NHLBI NIH HHS / United States
K24 DK080140-05 / DK / NIDDK NIH HHS / United States
N01 AG062101 / AG / NIA NIH HHS / United States
U01 HL080295 / HL / NHLBI NIH HHS / United States
5R01 HL08821502 / HL / NHLBI NIH HHS / United States
R01 DK075681-02 / DK / NIDDK NIH HHS / United States
N01 HC075150 / HC / NHLBI NIH HHS / United States
N01-HC-55022 / HC / NHLBI NIH HHS / United States
R01 HL059367 / HL / NHLBI NIH HHS / United States
5R01 DK06833603 / DK / NIDDK NIH HHS / United States
N01 HC015103 / HC / NHLBI NIH HHS / United States
M01 RR000069 / RR / NCRR NIH HHS / United States
N01-HC-55016 / HC / NHLBI NIH HHS / United States
K01 DK083029 / DK / NIDDK NIH HHS / United States
R01 HL086694 / HL / NHLBI NIH HHS / United States
P30 DK063491-03 / DK / NIDDK NIH HHS / United States
R01 HL086694-05 / HL / NHLBI NIH HHS / United States
R01 DK068336 / DK / NIDDK NIH HHS / United States
1R01AG032098-01A1 / AG / NIA NIH HHS / United States
R01 HL087652 / HL / NHLBI NIH HHS / United States
U01 HG004402 / HG / NHGRI NIH HHS / United States
N01HC55022 / HL / NHLBI NIH HHS / United States
N01 AG062106 / AG / NIA NIH HHS / United States
N01HC55222 / HL / NHLBI NIH HHS / United States
N01-HC-55021 / HC / NHLBI NIH HHS / United States
N02HL64278 / HL / NHLBI NIH HHS / United States
R01 DK075681 / DK / NIDDK NIH HHS / United States
N01-HC-85086 / HC / NHLBI NIH HHS / United States
N01HC55015 / HL / NHLBI NIH HHS / United States
K23 DK065978-05 / DK / NIDDK NIH HHS / United States
N01HC85086 / HL / NHLBI NIH HHS / United States
R01 AG032098-01A1 / AG / NIA NIH HHS / United States
M01 RR000069-46 / RR / NCRR NIH HHS / United States
U01HG004402 / HG / NHGRI NIH HHS / United States
K23 DK65978 / DK / NIDDK NIH HHS / United States
R01 AG032098 / AG / NIA NIH HHS / United States
R01 HL087641-03 / HL / NHLBI NIH HHS / United States
P30 DK063491 / DK / NIDDK NIH HHS / United States
HHSN268200782096C / HG / NHGRI NIH HHS / United States
5R01 DK07568102 / DK / NIDDK NIH HHS / United States
N01 HC-55222 / HC / NHLBI NIH HHS / United States
N01-HC-55019 / HC / NHLBI NIH HHS / United States
N01-HC- 85079 / HC / NHLBI NIH HHS / United States
R01HL087641 / HL / NHLBI NIH HHS / United States
N01-HC-55015 / HC / NHLBI NIH HHS / United States
N01 AG062103 / AG / NIA NIH HHS / United States
N1AG62103A / AG / NIA NIH HHS / United States
K24 DK080140 / DK / NIDDK NIH HHS / United States
M01RR00069 / RR / NCRR NIH HHS / United States
N01-HC-75150 / HC / NHLBI NIH HHS / United States
N01-HC-55020 / HC / NHLBI NIH HHS / United States
N01HC55016 / HL / NHLBI NIH HHS / United States
R01 HL087700-03 / HL / NHLBI NIH HHS / United States
N1AG62106A / AG / NIA NIH HHS / United States
R01 HL088215 / HL / NHLBI NIH HHS / United States
N01HC55019 / HL / NHLBI NIH HHS / United States
N01HC75150 / HL / NHLBI NIH HHS / United States
R01 DK089256 / DK / NIDDK NIH HHS / United States
U01 AG023746 / AG / NIA NIH HHS / United States
N01HC25195 / HL / NHLBI NIH HHS / United States
R01 DK068336-03 / DK / NIDDK NIH HHS / United States
DK063491 / DK / NIDDK NIH HHS / United States
N01HC85079 / HL / NHLBI NIH HHS / United States
R01 HL117078 / HL / NHLBI NIH HHS / United States
N01-HC-55018 / HC / NHLBI NIH HHS / United States
N01HC55021 / HL / NHLBI NIH HHS / United States
R01 HL087641 / HL / NHLBI NIH HHS / United States
N01 HC045133 / HC / NHLBI NIH HHS / United States
R01 HL087700 / HL / NHLBI NIH HHS / United States
K23 DK065978 / DK / NIDDK NIH HHS / United States
N01 HC035129 / HC / NHLBI NIH HHS / United States
R01HL086694 / HL / NHLBI NIH HHS / United States
U01 HG004402-02 / HG / NHGRI NIH HHS / United States

© 2001 - 2020 CHS Coordinating Center University of Washington, Seattle, WA

Privacy | Terms