國家衛生研究院 NHRI:Item 3990099045/13457
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    题名: Chromosome Xq23 is associated with lower atherogenic lipid concentrations and favorable cardiometabolic indices
    作者: Natarajan, P;Pampana, A;Graham, SE;Ruotsalainen, SE;Perry, JA;de Vries, PS;Broome, JG;Pirruccello, JP;Honigbere, MC;Aragam, K;Wolford, B;Brody, JA;Antonacci-Fulton, L;Arden, M;Aslibekyan, S;Assimes, TL;Ballantyne, CM;Bielak, LF;Bisl, JC;Cade, BE;Do, R;Doddapaneni, H;Emery, LS;Hung, YJ;Irvin, MR;Khan, AT;Lange, L;Lee, J;Lemaitre, RN;Martin, LW;Metcalf, G;Montasser, ME;Moon, JY;Muzny, D;Connell, JRO;Palmer, ND;Peralta, JM;Peyser, PA;Stilp, AM;Tsai, M;Wang, FF;Weeks, DE;Yanek, LR;Wilson, JG;Abecasis, G;Arnett, DK;Becker, LC;Blangercy, J;Boerwinkle, E;Bowden, DW;Chang, YC;Chen, YDI;Choi, WJ;Correa, A;Curran, JE;Daly, MJ;DutcherE, SK;Ellinor, PT;Fornage, M;Freedman, BI;Gabriel, S;Germer, S;Gibbs, RA;He, J;Hveem, K;Jarvik, GP;Kaplan, RC;Kardia, SLR;Kennyn, E;Kim, RW;Kooperberg, C;Laurie, CC;Lee, S;Lloyd-Jones, DM;Loos, RJF;Lubitz, SA;Mathias, RA;Martinez, KAV;McGarvey, ST;Mitche, BD;Nickerson, DA;North, KE;Palotie, A;Park, CJ;Psat, YBM;Rao, DC;Redline, S;Reiner, AP;Seo, D;Seo, JS;Smith, AV;Tracy, RP;Kathiresan, S;Cupples, LA;Rotten, JI;Morrison, AC;Rich, SS;Ripatti, S;Wilier, C;Peloso, GM, .;et al.
    贡献者: Institute of Population Health Sciences
    摘要: Autosomal genetic analyses of blood lipids have yielded key insights for coronary heart disease (CHD). However, X chromosome genetic variation is understudied for blood lipids in large sample sizes. We now analyze genetic and blood lipid data in a high-coverage whole X chromosome sequencing study of 65,322 multi-ancestry participants and perform replication among 456,893 European participants. Common alleles on chromosome Xq23 are strongly associated with reduced total cholesterol, LDL cholesterol, and triglycerides (min P=8.5x10(-72)), with similar effects for males and females. Chromosome Xq23 lipid-lowering alleles are associated with reduced odds for CHD among 42,545 cases and 591,247 controls (P=1.7x10(-4)), and reduced odds for diabetes mellitus type 2 among 54,095 cases and 573,885 controls (P=1.4x10(-5)). Although we observe an association with increased BMI, waist-to-hip ratio adjusted for BMI is reduced, bioimpedance analyses indicate increased gluteofemoral fat, and abdominal MRI analyses indicate reduced visceral adiposity. Co-localization analyses strongly correlate increased CHRDL1 gene expression, particularly in adipose tissue, with reduced concentrations of blood lipids. The influence of X chromosome genetic variation on blood lipids and coronary heart disease (CHD) is not well understood. Here, the authors analyse X chromosome sequencing data across 65,322 multi-ancestry individuals, identifying associations of the Xq23 locus with lipid changes and reduced risk of CHD and diabetes mellitus.
    日期: 2021-04-12
    關聯: Nature Communications. 2021 Apr 12;12:Article number 2182.
    Link to: http://dx.doi.org/10.1038/s41467-021-22339-1
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=2041-1723&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000640907200012
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85104367584
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