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Chunk #77 — 7.0 Recommendations to Advance Endophenotype Genetics — 7.2 GWAS to discover new variants associated with endophenotypes

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Endophenotype best practices.
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After quality control, phasing, imputation, and subsequent removal of poorly imputed or rare variants, a standard GWAS simply associates each of the variants with the quantitative phenotype. This essentially comprises millions of correlations in turn, one between the phenotype and each genetic variant. The next step involves determining which of the millions of variants are associated with the phenotype at a statistically significant level. The convention in GWASs of common variants (e.g., MAF > 1%) is to use the conventional alpha of .05 and a Bonferroni correction for 1 million tests, or .05/1,000,000 = 5×10−8. Testing all common variants, but then accounting for the non-independence among them due to linkage disequilibrium, is approximately equivalent to conducting 1 million independent tests; hence the convention.