國家衛生研究院 NHRI:Item 3990099045/13511
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    題名: Variant-specific inflation factors for assessing population stratification at the phenotypic variance level
    作者: Sofer, T;Zheng, X;Laurie, CA;Gogarten, SM;Brody, JA;Conomos, MP;Bis, JC;Thornton, TA;Szpiro, A;O’Connell, JR;Lange, EM;Gao, Y;Cupples, LA;Psaty, BM;Abe, N;Abecasis, G;Aguet, F;Albert, C;Almasy, L;Alonso, A;Ament, S;Anderson, P;Anugu, P;Applebaum-Bowden, D;Ardlie, K;Arking, D;Arnett, DK;Ashley-Koch, A;Aslibekyan, S;Assimes, T;Auer, P;Avramopoulos, D;Ayas, N;Balasubramanian, A;Barnard, J;Barnes, K;Barr, RG;Barron-Casella, E;Barwick, L;Beaty, T;Beck, G;Becker, D;Becker, L;Beer, R;Beitelshees, A;Benjamin, E;Benos, T;Bezerra, M;Bielak, L;Bis, J;Blackwell, T;Blangero, J;Boerwinkle, E;Bowden, DW;Bowler, R;Brody, J;Broeckel, U;Broome, J;Brown, D;Bunting, K;Burchard, E;Bustamante, C;Buth, E;Cade, B;Cardwell, J;Carey, V;Carrier, J;Carty, C;Casaburi, R;Romero, JPC;Casella, J;Castaldi, P;Chaffin, M;Chang, C;Chang, YC;Chasman, D;Chavan, S;Chen, BJ;Chen, WM;Chen, YDI;Cho, M;Choi, SH;Chuang, LM;Chung, M;Chung, RH;Clish, C;Comhair, S;Conomos, M;Cornell, E;Correa, A;Crandall, C;Crapo, J;Cupples, LA;Curran, J;Curtis, J;Custer, B;Damcott, C;Darbar, D;David, S;Davis, C;et al.
    貢獻者: Institute of Population Health Sciences
    摘要: In modern Whole Genome Sequencing (WGS) epidemiological studies, participant-level data from multiple studies are often pooled and results are obtained from a single analysis. We consider the impact of differential phenotype variances by study, which we term ‘variance stratification’. Unaccounted for, variance stratification can lead to both decreased statistical power, and increased false positives rates, depending on how allele frequencies, sample sizes, and phenotypic variances vary across the studies that are pooled. We develop a procedure to compute variant-specific inflation factors, and show how it can be used for diagnosis of genetic association analyses on pooled individual level data from multiple studies. We describe a WGS-appropriate analysis approach, implemented in freely-available software, which allows study-specific variances and thereby improves performance in practice. We illustrate the variance stratification problem, its solutions, and the proposed diagnostic procedure, in simulations and in data from the Trans-Omics for Precision Medicine Whole Genome Sequencing Program (TOPMed), used in association tests for hemoglobin concentrations and BMI.
    日期: 2021-06-09
    關聯: Nature Communications. 2021 Jun 9;12:Article number 3506.
    Link to: http://dx.doi.org/10.1038/s41467-021-23655-2
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=2041-1723&DestApp=IC2JCR
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85107746519
    顯示於類別:[鍾仁華] 期刊論文
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