Finner, Helmut and Strassburger, Klaus and Heid, Iris M. and Herder, Christian and Rathmann, Wolfgang and Giani, Guido and Dickhaus, Thorsten and Lichtner, Peter and Meitinger, Thomas and Wichmann, H. -Erich and Illigg, Thomas and Gieger, Christian (2010) How to link call rate and p-values for Hardy-Weinberg equilibrium as measures of genome-wide SNP data quality. STATISTICS IN MEDICINE, 29 (22). pp. 2347-2358. ISSN 0277-6715, 1097-0258
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We study the link between two quality measures of SNP (single nucleotide polymorphism) data in genome-wide association (GWA) studies, that is, per SNP call rates (CR) and p-values for testing Hardy-Weinberg equilibrium (HWE). The aim is to improve these measures by applying methods based on realized randomized p-values, the false discovery rate and estimates for the proportion of false hypotheses. While exact non-randomized conditional p-values for testing HWE cannot be recommended for estimating the proportion of false hypotheses, their realized randomized counterparts should be used. P-values corresponding to the asymptotic unconditional chi-square test lead to reasonable estimates only if SNPs with low minor allele frequency are excluded. We provide an algorithm to compute the probability that SNPs violate HWE given the observed CR, which yields an improved measure of data quality. The proposed methods are applied to SNP data from the KORA (Cooperative Health Research in the Region of Augsburg, Southern Germany) 500 K project, a GWA study in a population-based sample genotyped by Affymetrix GeneChip 500 K arrays using the calling algorithm BRLMM 1.4.0. We show that all SNPs with CR = 100 per cent are nearly in perfect HWE which militates in favor of the population to meet the conditions required for HWE at least for these SNPs. Moreover, we show that the proportion of SNPs not being in HWE increases with decreasing CR. We conclude that using a single threshold for judging HWE p-values without taking the CR into account is problematic. Instead we recommend a stratified analysis with respect to CR. Copyright (C) 2010 John Wiley & Sons, Ltd.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | FALSE DISCOVERY RATE; GENOTYPING ERRORS; UNIFIED APPROACH; EMPIRICAL BAYES; TESTS; KORA; PROPORTION; GENETICS; GENES; false discovery rate; genome-wide association (GWA) studies; genotyping errors; multiple comparisons; multiple hypotheses testing; quality control; randomized p-values |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Institut für Epidemiologie und Präventivmedizin |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 13 Jul 2020 06:11 |
| Last Modified: | 13 Jul 2020 06:11 |
| URI: | https://pred.uni-regensburg.de/id/eprint/24159 |
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