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. 2020 Nov 24;21(1):130.
doi: 10.1186/s12863-020-00951-2.

Identifying rare variants for quantitative traits in extreme samples of population via Kullback-Leibler distance

Yang Xiang  1   2   3 , Xinrong Xiang  4 , Yumei Li  5   6   7
Affiliations

Identifying rare variants for quantitative traits in extreme samples of population via Kullback-Leibler distance

Yang Xiang et al. BMC Genet. .

Abstract

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.

Keywords: Association analysis; Extreme phenotype; Fine mapping; Quantitative trait; Rare variant.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Empirical power of four statistics from the extreme samples with 20% threshold value a, 10% threshold value b, and 5% threshold value c when the sample sizes are 1000 (a1, b1, c1) and 1500 (a2, b2, c2) at a 0.05 significance level
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References

    1. Cirulli ET, Goldstein DB. Uncovering the roles of rare variants in common disease through whole-genome sequencing. Nat Rev Genet. 2010;11(6):415–425. doi: 10.1038/nrg2779. - DOI - PubMed
    1. Visscher PM, Brown MA, McCarthy MI, Yang J. Five years of GWAS discovery. Am J Hum Genet. 2012;90(1):7–24. doi: 10.1016/j.ajhg.2011.11.029. - DOI - PMC - PubMed
    1. Manolio TA, Collins FS, Cox NJ, Goldstein DB, Hin-dorff LA, Hunter DJ, et al. Finding the missing heritability of complex diseases. Nature. 2009;461(7265):747–753. doi: 10.1038/nature08494. - DOI - PMC - PubMed
    1. Fu W, O’Connor TD, Jun G, Kang HM, Abecasis G, Leal SM, et al. Analysis of 6,515 exomes reveals the recent origin of most human protein-cod-ing variants. Nature. 2013;493(7431):216–220. doi: 10.1038/nature11690. - DOI - PMC - PubMed
    1. Nelson MR, Wegmann D, Ehm MG, Kessner D, St Jean P, Verzilli C, et al. An abundance of rare functional variants in 202 drug target genes sequenced in 14,002 people. Science. 2012;337(6090):100–104. doi: 10.1126/science.1217876. - DOI - PMC - PubMed

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