GENOME-WIDE ANALYSIS OF 102,084 MIGRAINE CASES IDENTIFIES 123 RISK LOCI AND SUBTYPE-SPECIFIC RISK ALLELES 163 8 Table 2 Study collections included in MO and MA subtype analyses Abbreviation Full name Ancestry Subtype Cases Controls IHGC2016* Gormley et al. 2016 European descent MO 8,348 139,622 MA 6,332 144,883 UKBB UK Biobank (ukbiobank.ac.uk) European, British MO 187 320,139 MA 1,333 320,139 deCODE deCODE Genetics Inc. European, Icelandic MO 1,648 193,050 MA 2,297 209,338 DBDS Danish Blood Donor Study European, Danish MO 3,756 28,045 MA 3,938 28,045 LUMINA LUMINA migraine without aura or with aura European, Dutch MO 1,116 1,445 MA 724 1,447 *IHGC2016 MO is a meta-analysis of 11 studies and IHGC2016 MA is a meta-analysis of 12 studies listed in Gormley et al. 2016. MO, migraine without aura; MA, migraine with aura. Quality control Before the meta-analysis, a standard quality control protocol was applied to each individual GWAS. Related individuals were removed from all other cohorts except HUNT (which modeled relatedness via a logistic mixed model) by using an IBD cut-off of 0.185 or smaller. Multi-allelic variants were excluded from all studies, and only variants that satisfied the following thresholds were kept for further analysis: minor allele frequency (MAF) > 0.01, IMPUTE2 info or MACH r2 > 0.6, and, when available, Hardy-Weinberg equilibrium (HWE) P-value > 1 × 10-6 and missingness < 0.05. Variants were matched by chromosome, position and alleles to the UK Biobank data. Indels were recoded as insertions (I) and deletions (D). For each study, the SNPs with an effect allele frequency (EAF) discrepancy of > 0.30 and indels with EAF discrepancy of > 0.20 to UK Biobank were excluded. MAF and EAF plots of cohorts against the reference cohort are shown in Supplementary Data 7. We conducted a sensitivity analysis on strand-ambiguous SNPs (with alleles A/T or G/C), by counting, for each pair of studies, how often the same allele of A/T or G/C SNP was coded as the minor allele in both cohorts, as a function of MAF threshold (Supplementary Table 17). Minor alleles were same at least in 97.39% of the SNPs without MAF threshold and the corresponding proportions were 99.96% and 79.58% when MAF < 0.25 and when MAF > 0.4, respectively. The very high concordance for SNPs with MAF < 0.25 suggests that the strand-ambiguous SNPs were consistently labeled for almost every SNP.Therefore, we did not exclude any SNPs based on possible labeling mismatches due to strand ambiguity. Statistical analysis All statistical tests conducted were two-sided unless otherwise indicated. The GWAS for the individual study cohorts were performed by logistic regression with an additive model of imputed dosage of the effect allele on the log-odds of migraine. The analyses for IHGC201613 and 23andMe19 have been described before. For UKBB data and GeneRISK data, we used PLINK
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