Chromosome Xq23 is associated with lower atherogenic lipid concentrations and favorable cardiometabolic indices.
Chromosome Xq23 is associated with lower atherogenic lipid concentrations and favorable cardiometabolic indices.
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DOI：
10.1038/s41467-021-22339-1
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发表时间：
2021-04-12
影响因子：
16.6
通讯作者：
Peloso GM
中科院分区：
文献类型：
--
作者：
Natarajan P;Pampana A;Graham SE;Ruotsalainen SE;Perry JA;de Vries PS;Broome JG;Pirruccello JP;Honigberg MC;Aragam K;Wolford B;Brody JA;Antonacci-Fulton L;Arden M;Aslibekyan S;Assimes TL;Ballantyne CM;Bielak LF;Bis 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;O'Connell JR;Palmer ND;Peralta JM;Peyser PA;Stilp AM;Tsai M;Wang FF;Weeks DE;Yanek LR;Wilson JG;Abecasis G;Arnett DK;Becker LC;Blangero J;Boerwinkle E;Bowden DW;Chang YC;Chen YI;Choi WJ;Correa A;Curran JE;Daly MJ;Dutcher SK;Ellinor PT;Fornage M;Freedman BI;Gabriel S;Germer S;Gibbs RA;He J;Hveem K;Jarvik GP;Kaplan RC;Kardia SLR;Kenny E;Kim RW;Kooperberg C;Laurie CC;Lee S;Lloyd-Jones DM;Loos RJF;Lubitz SA;Mathias RA;Martinez KAV;McGarvey ST;Mitchell BD;Nickerson DA;North KE;Palotie A;Park CJ;Psaty BM;Rao DC;Redline S;Reiner AP;Seo D;Seo JS;Smith AV;Tracy RP;Vasan RS;Kathiresan S;Cupples LA;Rotter JI;Morrison AC;Rich SS;Ripatti S;Willer C;NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium;FinnGen;Peloso GM
对血脂的常染色体遗传分析已经为冠心病(CHD)提供了关键的见解。然而，在大样本中，对血脂的X染色体遗传变异的研究还不够深入。我们现在分析高覆盖率的全X染色体测序研究中的遗传和血脂数据，研究对象为65,322名多血统参与者，并在456,893名欧洲参与者中进行复制。染色体Xq23上的常见等位基因与总胆固醇、低密度脂蛋白和甘油三酯的降低密切相关(Min P = 8.5 × 10−72)，对男性和女性的影响相似。在42,545例患者和591,247名对照中，Xq23降脂等位基因降低了冠心病的患病几率(P = 1.7 × 10−4)；在54,095例病例和573,885名对照中，Xq23等位基因降低了2型糖尿病的发病几率(P = 1.4 × 10−5)。虽然我们观察到BMI增加与腰臀比降低有关，但生物阻抗分析显示臀部股脂肪增加，腹部MRI分析显示内脏脂肪减少。共定位分析与CHRDL1基因表达的增加密切相关，特别是在脂肪组织中，与降低血脂浓度密切相关。X染色体遗传变异对血脂和冠心病(CHD)的影响尚不清楚。在这里，作者分析了65,322名多血统个体的X染色体测序数据，确定了Xq23基因座与血脂变化和降低冠心病和糖尿病风险的关联。
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 = 8.5 × 10−72), 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 = 1.7 × 10−4), and reduced odds for diabetes mellitus type 2 among 54,095 cases and 573,885 controls (P = 1.4 × 10−5). 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.
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影响因子：
64.8
作者：
Bycroft C;Freeman C;Petkova D;Band G;Elliott LT;Sharp K;Motyer A;Vukcevic D;Delaneau O;O'Connell J;Cortes A;Welsh S;Young A;Effingham M;McVean G;Leslie S;Allen N;Donnelly P;Marchini J
通讯作者：
Marchini J
腰围比与心脏代谢性状，2型糖尿病和冠状动脉疾病的遗传关联。
DOI：
10.1001/jama.2016.21042
发表时间：
2017-02-14
期刊：
JAMA
影响因子：
--
作者：
Emdin CA;Khera AV;Natarajan P;Klarin D;Zekavat SM;Hsiao AJ;Kathiresan S
通讯作者：
Kathiresan S
影响因子：
46.9
作者：
通讯作者：
--
英国生物库中的遗传分析将胰岛素抵抗和跨内皮迁移途径与冠状动脉疾病联系起来。
影响因子：
30.8
作者：
Klarin D;Zhu QM;Emdin CA;Chaffin M;Horner S;McMillan BJ;Leed A;Weale ME;Spencer CCA;Aguet F;Segrè AV;Ardlie KG;Khera AV;Kaushik VK;Natarajan P;CARDIoGRAMplusC4D Consortium;Kathiresan S
通讯作者：
Kathiresan S
影响因子：
2.1
作者：
Conomos MP;Miller MB;Thornton TA
通讯作者：
Thornton TA