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Chunk #49 — Methods — An optimization framework for selecting the number of SNPs to follow-up

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Integrating functional data to prioritize causal variants in statistical fine-mapping studies.
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The budget of a fine mapping follow-up study constrains the total number of causal variants to be further examined for evidence of causality. This motivates approaches that, in addition to providing a prioritization of SNPs, also identify an optimal number of SNPs to be tested. We introduce here a benefit-to-cost framework for selecting the optimal number of SNPs for follow-up. Our framework assumes that every causal variant identified adds a benefit (B) while every selected variant is tested at a cost (C); therefore, the utility function we propose to maximize is U = B*Nc - C*Nt, where Nc is the total number of true causal variants identified from the total number of selected SNPs. A key parameter of the utility framework is the ratio of of benefit to utility.