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Chunk #16 — Introduction — From loci to genes

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Interpretation of risk loci from genome-wide association studies of Alzheimer's disease.
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Several methods prioritise candidate causal variants and genes within loci.32,35 Conditional analysis attempts to identify whether there are multiple independent signals within a locus by iterative use of traditional genetic association methods,35 repeatedly covarying on top variants until no signal remains, but requires raw genetic data and is somewhat stringent; it ignores variants with truly independent effects on genes if they are in strong linkage disequilibrium with lead SNPs. Other statistical fine–mapping methods use either raw data or summary statistics to predict less stringent sets of variants that are likely to be causal on the basis of association statistics and the linkage disequilibrium structure of the locus.35 Genomic annotation can then be used to assign biological function to the variants selected via fine mapping to further prioritise likely functional variants.