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Erschienen in: European Journal of Epidemiology 8/2010

01.08.2010 | GENETIC EPIDEMIOLOGY

Impact of Hardy–Weinberg equilibrium deviation on allele-based risk effect of genetic association studies and meta-analysis

verfasst von: Elias Zintzaras

Erschienen in: European Journal of Epidemiology | Ausgabe 8/2010

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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.
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Metadaten
Titel
Impact of Hardy–Weinberg equilibrium deviation on allele-based risk effect of genetic association studies and meta-analysis
verfasst von
Elias Zintzaras
Publikationsdatum
01.08.2010
Verlag
Springer Netherlands
Erschienen in
European Journal of Epidemiology / Ausgabe 8/2010
Print ISSN: 0393-2990
Elektronische ISSN: 1573-7284
DOI
https://doi.org/10.1007/s10654-010-9467-z

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