Identifying rare variants for quantitative traits in extreme samples of population via Kullback-Leibler distance
2020
Xiang, Yang | Xiang, Xinrong | Li, Yumei
BACKGROUND: The rapid development of sequencing technology and simultaneously the availability of large quantities of sequence data has facilitated the identification of rare variant associated with quantitative traits. However, existing statistical methods depend on certain assumptions and thus lacking uniform power. The present study focuses on mapping rare variant associated with quantitative traits. RESULTS: In the present study, we proposed a two-stage strategy to identify rare variant of quantitative traits using phenotype extreme selection design and Kullback-Leibler distance, where the first stage was association analysis and the second stage was fine mapping. We presented a statistic and a linkage disequilibrium measure for the first stage and the second stage, respectively. Theory analysis and simulation study showed that (1) the power of the proposed statistic for association analysis increased with the stringency of the sample selection and was affected slightly by non-causal variants and opposite effect variants, (2) the statistic here achieved higher power than three commonly used methods, and (3) the linkage disequilibrium measure for fine mapping was independent of the frequencies of non-causal variants and simply dependent on the frequencies of causal variants. CONCLUSIONS: We conclude that the two-stage strategy here can be used effectively to mapping rare variant associated with quantitative traits.
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