University of Ioannina

About: University of Ioannina is a education organization based out in Ioannina, Greece. It is known for research contribution in the topics: Population & Large Hadron Collider. The organization has 7654 authors who have published 20594 publications receiving 671560 citations. The organization is also known as: Panepistimio Ioanninon.

Impact of violations and deviations in Hardy-Weinberg equilibrium on postulated gene-disease associations.

Abstract: The authors evaluated whether statistically significant violations of Hardy-Weinberg equilibrium (HWE) or the magnitude of deviations from HWE may contribute to the problem of replicating postulated gene-disease associations across different studies Forty-two gene-disease associations assessed in meta-analyses of 591 studies were examined Studies with disease-free controls in which HWE was violated gave significantly different results from HWE-conforming studies in five instances Exclusion of the former studies resulted in loss of statistical significance of the overall meta-analysis in three instances and more than a 10% change in the summary odds ratio in six Exclusion of HWE-violating studies changed the formal significance of the estimated between-study heterogeneity in three instances After adjustment for the magnitude of the deviation from HWE for the controls, formal significance was lost in another three instances Studies adjusted for the magnitude of deviation from HWE tended to become more heterogeneous among themselves, and, for seven gene-disease associations, between-study heterogeneity became significant, while it was not so in the unadjusted analyses Gene-disease association studies and meta-analyses thereof should routinely scrutinize the potential impact of HWE violations as well as nonsignificant deviations from the exact frequencies expected under HWE Postulated genetic associations with modest-sized odds ratios and borderline statistical significance may not be robust in such sensitivity analyses

What should the genome-wide significance threshold be? Empirical replication of borderline genetic associations

Abstract: Background Robust replication is a sine qua non for the rigorous documentation of proposed associations in the genome-wide association (GWA) setting. Currently, associations of common variants reaching P ≤ 5 × 10(-8) are considered replicated. However, there is some ambiguity about the most suitable threshold for claiming genome-wide significance. Methods We defined as 'borderline' associations those with P > 5 × 10(-8) and P ≤ 1 × 10(-7). The eligible associations were retrieved using the 'Catalog of Published Genome-Wide Association Studies'. For each association we assessed whether it reached P ≤ 5 × 10(-8) with inclusion of additional data from subsequent GWA studies. Results Thirty-four eligible genotype-phenotype associations were evaluated with data and clarifications contributed from diverse investigators. Replication data from subsequent GWA studies could be obtained for 26 of them. Of those, 19 associations (73%) reached P ≤ 5 × 10(-8) for the same or a related trait implicating either the exact same allele or one in very high linkage disequilibrium and 17 reached P 10(-6) [corresponding false-discovery rate 19% (95% CI 7-39%)]. Conclusion A substantial proportion, but not all, of the associations with borderline genome-wide significance represent replicable, possibly genuine associations. Our empirical evaluation suggests a possible relaxation in the current GWS threshold.