Genetic variants associated with earlier age at menopause increase the risk of cardiovascular events in women

被引：23

作者：

Sarnowski, Chloe ^{[1
]}

Kavousi, Maryam ^{[2
]}

Isaacs, Steve ^{[3
]}

Demerath, Ellen W. ^{[4
]}

Broer, Linda

Muka, Taulant ^{[2
]}

Franco, Oscar H. ^{[2
]}

Ikram, Mohammad Arfan ^{[2
]}

Uitterlinden, Andre ^{[2
,5
]}

Franceschini, Nora ^{[3
]}

Lunetta, Kathryn L. ^{[1
]}

Murabito, Joanne M. ^{[6
,7
]}

机构：

[1] Boston Univ, Dept Biostat, Sch Publ Hlth, 801 Massachusetts Ave,3rd Floor,CT346, Boston, MA 02118 USA

[2] Univ Med Ctr Rotterdam, Dept Epidemiol, Erasmus MC, Rotterdam, Netherlands

[3] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27515 USA

[4] Univ Minnesota, Dept Epidemiol & Community Hlth, Minneapolis, MN USA

[5] Univ Med Ctr Rotterdam, Dept Internal Med, Erasmus MC, Rotterdam, Netherlands

[6] Framingham Heart Dis Epidemiol Study, Framingham, MA USA

[7] Boston Univ, Sch Med, Dept Med, Gen Internal Med Sect, Boston, MA 02118 USA

来源：

MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY | 2018年 / 25卷 / 04期

关键词：

Age-at-natural menopause; Cardiovascular disease; DNA damage response pathway; Genetic correlation; Genetic risk score; Pleiotropy; BREAST-CANCER SUSCEPTIBILITY; GENOME-WIDE ASSOCIATION; DNA-DAMAGE; NATURAL MENOPAUSE; HEART-DISEASE; REPAIR; ATHEROSCLEROSIS; LOCI;

D O I：

10.1097/GME.0000000000001017

中图分类号：

R71 [妇产科学];

学科分类号：

100211 ;

摘要：

Objective: To better understand the relationship between cardiovascular disease risk and age-at-natural menopause using genetic data. Methods: Early menopause is associated with cardiovascular disease risk. We constructed a genetic risk score comprising 56 age-at-natural menopause decreasing alleles in men and women from the Framingham Heart Study, the Atherosclerosis Risk in Communities Study, and the Rotterdam Study. If the genetic predisposition to earlier age-at-natural menopause is associated with increased cardiovascular disease risk, it is reasonable to ask whether the risk is shared by men carrying the alleles, despite not experiencing menopause. We estimated the hazard ratio for the score for time to first cardiovascular event. To investigate the possible genetic pleiotropy between age-at-natural menopause and cardiovascular disease, we performed cross-trait linkage disequilibrium score regressions between age-at-natural menopause and cardiovascular disease and risk factors using genome-wide association studies. Results: Twenty-two thousand five hundred and sixty-eight cardiovascular disease-free participants at baseline were analyzed (9,808 men, 12,760 women). Each additional unit of the genetic propensity to earlier age-at-natural menopause increased the hazard of both cardiovascular disease and cardiac death in women (cardiovascular disease: hazard ratio 1.10 [1.04-1.16], P = 9.7 x 10(-4); cardiac death: 1.12 [1.02-1.24], P = 0.03), whereas no effect was observed for either outcome in men (hazard ratio 0.99 [0.95-1.04], P = 0.71; 1.05 [0.94-1.16], P = 0.34). We found significant negative genetic correlations in women, but not men, between age-at-natural menopause and cardiovascular disease and risk factors. Conclusion: Genetic variants associated with earlier age-at-natural menopause are associated with increased cardiovascular disease risk inwomen, but not men, suggesting sex-specific genetic effects on cardiovascular disease risk.

引用

页码：451 / 457

页数：7

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