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Chunk #32 — Methods — Statistical Methods

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A genome-wide association study reveals variants in ARL15 that influence adiponectin levels.
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We declared statistical significance in the GWAS as P≤5×10−8, where this threshold is based on a Bonferroni correction of α = 0.05 divided by one million, the estimated number of independent common tests among common SNPs in the CEU population of the HapMap II project [57]. Using this threshold, 5 SNPs achieved genome-wide significance for their relationship with circulating adiponectin levels in the combined analysis of all adiponectin cohorts. These were subsequently tested for their association with glycated hemoglobin, indices of insulin resistance, beta-cell function and risk of T2D and CHD. The number of independent statistical tests represented by these 5 SNPs, accounting for linkage disequilibrium at ADIPOQ, was assessed by spectral decomposition of matrices of pairwise linkage disequilibrium between the 4 SNPs at the ADIPOQ locus [58]. In total, 3.59 independent statistical tests were performed at this locus, and one at the ARL15 locus. Thus, statistical significance in the follow-up studies was declared at P≤0.011 (based on a Bonferroni correction of α = 0.05 divided by 4.59, the number of statistically independent SNPs tested in the follow-up analyses).