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A robust method for genome-wide association meta-analysis with the application to circulating insulin-like growth factor I concentrations.
Tuesday,2014-04-01 13:21 America/Los_Angeles — poolea2
| Title | A robust method for genome-wide association meta-analysis with the application to circulating insulin-like growth factor I concentrations. |
| Publication Type | Journal Article |
| Year of Publication | 2014 |
| Authors | Wang, T, Zhou, B, Guo, T, Bidlingmaier, M, Wallaschofski, H, Teumer, A, Vasan, RS, Kaplan, RC |
| Journal | Genet Epidemiol |
| Volume | 38 |
| Issue | 2 |
| Pagination | 162-71 |
| Date Published | 2014 Feb |
| ISSN | 1098-2272 |
| Keywords | Computer Simulation, Genetic Linkage, Genome, Genome-Wide Association Study, Humans, Insulin-Like Growth Factor I, Meta-Analysis as Topic, Models, Genetic, Polymorphism, Single Nucleotide, Sample Size |
| Abstract | <p>Genome-wide association studies (GWAS) offer an excellent opportunity to identify the genetic variants underlying complex human diseases. Successful utilization of this approach requires a large sample size to identify single nucleotide polymorphisms (SNPs) with subtle effects. Meta-analysis is a cost-efficient means to achieve large sample size by combining data from multiple independent GWAS; however, results from studies performed on different populations can be variable due to various reasons, including varied linkage equilibrium structures as well as gene-gene and gene-environment interactions. Nevertheless, one should expect effects of the SNP are more similar between similar populations than those between populations with quite different genetic and environmental backgrounds. Prior information on populations of GWAS is often not considered in current meta-analysis methods, rendering such analyses less optimal for the detecting association. This article describes a test that improves meta-analysis to incorporate variable heterogeneity among populations. The proposed method is remarkably simple in computation and hence can be performed in a rapid fashion in the setting of GWAS. Simulation results demonstrate the validity and higher power of the proposed method over conventional methods in the presence of heterogeneity. As a demonstration, we applied the test to real GWAS data to identify SNPs associated with circulating insulin-like growth factor I concentrations. </p> |
| DOI | 10.1002/gepi.21766 |
| Alternate Journal | Genet. Epidemiol. |
| PubMed ID | 24446417 |
| PubMed Central ID | PMC4049273 |
| Grant List | M01-RR00425 / RR / NCRR NIH HHS / United States N01-HC-25195 / HC / NHLBI NIH HHS / United States R21 HG006150 / HG / NHGRI NIH HHS / United States N01 HC085081 / HC / NHLBI NIH HHS / United States N01HC85080 / HC / NHLBI NIH HHS / United States U01 HL080295 / HL / NHLBI NIH HHS / United States HHSN268200800007C / HL / NHLBI NIH HHS / United States N01 HC015103 / HC / NHLBI NIH HHS / United States N01 HC085083 / HC / NHLBI NIH HHS / United States N01 HC025195 / HC / NHLBI NIH HHS / United States N02 HL64278 / HL / NHLBI NIH HHS / United States R01 HL087652 / HL / NHLBI NIH HHS / United States N01HC55222 / HL / NHLBI NIH HHS / United States N01HC85086 / HL / NHLBI NIH HHS / United States N01HC45133 / HC / NHLBI NIH HHS / United States N01 HC085082 / HC / NHLBI NIH HHS / United States N01HC85081 / HC / NHLBI NIH HHS / United States P30 DK063491 / DK / NIDDK NIH HHS / United States N01 HC085080 / HC / NHLBI NIH HHS / United States N01HC85079 / HC / NHLBI NIH HHS / United States HHSN268201200036C / HL / NHLBI NIH HHS / United States AG031890 / AG / NIA NIH HHS / United States N01HC85086 / HC / NHLBI NIH HHS / United States R01 HL080295 / HL / NHLBI NIH HHS / United States N01HC85082 / HC / NHLBI NIH HHS / United States M01 RR000425 / RR / NCRR NIH HHS / United States R01HL087652 / HL / NHLBI NIH HHS / United States N01HC85082 / HL / NHLBI NIH HHS / United States N01HC75150 / HL / NHLBI NIH HHS / United States N01HC85083 / HL / NHLBI NIH HHS / United States N01HC25195 / HL / NHLBI NIH HHS / United States DK063491 / DK / NIDDK NIH HHS / United States HL080295 / HL / NHLBI NIH HHS / United States N01HC85083 / HC / NHLBI NIH HHS / United States U01HL080295 / HL / NHLBI NIH HHS / United States N01HC85079 / HL / NHLBI NIH HHS / United States N01 HC085079 / HC / NHLBI NIH HHS / United States R01 AG023629 / AG / NIA NIH HHS / United States N01HC35129 / HC / NHLBI NIH HHS / United States N01 HC045133 / HC / NHLBI NIH HHS / United States N01HC85080 / HL / NHLBI NIH HHS / United States AG023629 / AG / NIA NIH HHS / United States R01 AG031890 / AG / NIA NIH HHS / United States P01 HD070454 / HD / NICHD NIH HHS / United States N01 HC035129 / HC / NHLBI NIH HHS / United States R56 AG023629 / AG / NIA NIH HHS / United States R21HG006150 / HG / NHGRI NIH HHS / United States N01HC85081 / HL / NHLBI NIH HHS / United States N01 HC55222 / HC / NHLBI NIH HHS / United States P01HD070454 / HD / NICHD NIH HHS / United States |