dc.creator | Zintzaras, E. | en |
dc.date.accessioned | 2015-11-23T10:55:06Z | |
dc.date.available | 2015-11-23T10:55:06Z | |
dc.date.issued | 2010 | |
dc.identifier | 10.1007/s10654-010-9467-z | |
dc.identifier.issn | 0393-2990 | |
dc.identifier.uri | http://hdl.handle.net/11615/34926 | |
dc.description.abstract | Deviations from Hardy-Weinberg equilibrium (HWE) in control subjects may bias the estimates of genetic effects in genetic association studies (GAS) and meta-analysis. A large empirical evaluation was carried out to evaluate the impact of HWE deviation and explore the effect of variance adjustment for the allele-based odds ratio in 833 individual GAS and 72 meta-analyses. In individual GAS, the variance adjustment for any deviation from HWE resulted in stronger associations, and 10 GAS (1%) became significant (P < 0.05). One hundred sixteen GAS (14%) showed significant deviation from HWE (P (HWE) < 0.05); however, only 37 GAS (4%) had more than 90% power to detect significant deviation from HWE at the 5% level. In meta-analyses, adjustment for any deviation from HWE improved the significance in 53 meta-analyses (74%). Then, a formal statistical significance (P < 0.05) was revealed for one previously negative meta-analyses whereas one meta-analysis lost its significance. Between-study heterogeneity was enhanced in 50 meta-analyses (69%). None of the meta-analyses lost the significance of heterogeneity (P (Q) < 0.10) whereas in one meta-analysis, the non significant heterogeneity became significant. Sensitivity analysis for studies not conforming to HWE (P (HWE) < 0.05) was applied to 45 meta-analyses (69%). Then, the significance of association was increased in 26 the meta-analyses (58%) and one meta-analysis became significant (P < 0.05) whereas seven meta-analyses (16%) were no longer significant. Adjustment for HWE deviation could be an effective strategy for dealing with HWE violations in GAS and meta-analyses. | en |
dc.source | European Journal of Epidemiology | en |
dc.source.uri | <Go to ISI>://WOS:000280907500005 | |
dc.subject | Hardy-Weinberg equilibrium | en |
dc.subject | HWE | en |
dc.subject | Adjustment | en |
dc.subject | Bias | en |
dc.subject | Odds ratio | en |
dc.subject | Power | en |
dc.subject | Variance | en |
dc.subject | Genetic association study | en |
dc.subject | Meta-analysis | en |
dc.subject | Gene | en |
dc.subject | Polymorphism | en |
dc.subject | Association | en |
dc.subject | DISEASE ASSOCIATIONS | en |
dc.subject | INFORMATION | en |
dc.subject | GENOTYPES | en |
dc.subject | TESTS | en |
dc.subject | Public, Environmental & Occupational Health | en |
dc.title | Impact of Hardy-Weinberg equilibrium deviation on allele-based risk effect of genetic association studies and meta-analysis | en |
dc.type | journalArticle | en |