Impact of genetic risk and lifestyles on cardiovascular disease-free and total life expectancy: a cohort study.

IF 10.4 1区 生物学 Q1 GENETICS & HEREDITY
Dong Sun, Qiufen Sun, Yinqi Ding, Canqing Yu, Dianjianyi Sun, Yuanjie Pang, Pei Pei, Ling Yang, Iona Y Millwood, Robin G Walters, Huaidong Du, Jun Zhang, Dan Schmidt, Junshi Chen, Zhengming Chen, Liming Li, Jun Lv
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引用次数: 0

Abstract

Background: Understanding the role of genetic risk and lifestyles on life expectancy (LE) without cardiovascular disease (CVD) and total LE may help optimize healthy aging strategies after taking genetic background into account.

Methods: The China Kadoorie Biobank recruited participants from five urban and five rural areas across China during 2004-2008 and followed them up till December 31, 2018. A polygenic risk score (PRS) comprising 3.5 million genetic variants for overall CVD was constructed by combining multiple PRSs for CVD and CVD-related risk factors in 96,400 participants. Genetic risk was categorized into low, intermediate, and high according to the PRS, and lifestyles were categorized as favorable, intermediate, and unfavorable according to the number of unfavorable lifestyles. Using multistate life tables, we estimated CVD-free and total LE at age 40 for different genetic and lifestyle risk groups.

Results: Genetic risk was more strongly associated with CVD onset than post-CVD mortality. As a result, the increase in LE without CVD associated with low genetic risk (4.9 years (95% CI 4.3-5.5) for women and 4.4 years (3.6-5.1) for men) was greater than the increase in total LE (2.9 years (1.8-3.8) for women and 2.6 years (1.5-3.5) for men) when compared to high genetic risk. In contrast, the association strengths of lifestyles with CVD onset and mortality after CVD were similar. Correspondingly, compared to those with unfavorable lifestyles, participants with favorable lifestyles had longer total LE and LE without CVD of 3.0 (1.5-4.3) and 4.0 (3.0-4.9) years in women and 5.7 (4.1-7.1) and 5.8 (4.7-6.9) years in men, respectively. Participants with high genetic risk benefited more from favorable lifestyles than those with low and intermediate genetic risk, gaining 5.9 (2.3-9.3) and 5.3 (3.0-7.6) years in women and 6.1 (0.8-10.6) and 6.2 (2.3-9.8) years in men for total and CVD-free LE, respectively.

Conclusions: Improving lifestyles is critical for reducing CVD-related healthcare burden and promoting healthy aging, especially for individuals with high genetic risk.

遗传风险和生活方式对无心血管疾病和总预期寿命的影响:一项队列研究
背景:了解遗传风险和生活方式对无心血管疾病(CVD)预期寿命(LE)和总寿命的影响,可能有助于在考虑遗传背景后优化健康老龄化策略。方法:中国嘉道理生物库在2004-2008年期间从中国五个城市和五个农村地区招募参与者,并随访至2018年12月31日。通过结合96,400名参与者的心血管疾病和心血管疾病相关危险因素的多个多基因风险评分(PRS),构建了包含350万个总体心血管疾病遗传变异的多基因风险评分(PRS)。根据PRS将遗传风险分为低、中、高,根据不良生活方式的数量将生活方式分为有利、中等、不利。使用多状态生命表,我们估计了不同遗传和生活方式风险群体在40岁时无cvd和总LE。结果:遗传风险与CVD发病的相关性高于CVD后死亡率。因此,与高遗传风险相比,无心血管疾病的低遗传风险(女性4.9年(95% CI 4.3-5.5),男性4.4年(3.6-5.1))的LE增加大于总LE增加(女性2.9年(1.8-3.8),男性2.6年(1.5-3.5))。相反,生活方式与CVD发病和CVD后死亡率的关联强度相似。相应地,与不良生活方式的参与者相比,良好生活方式的参与者的总LE和无CVD的LE更长,女性分别为3.0(1.5-4.3)和4.0(3.0-4.9)年,男性分别为5.7(4.1-7.1)和5.8(4.7-6.9)年。与低遗传风险和中等遗传风险的参与者相比,高遗传风险的参与者从良好的生活方式中获益更多,女性的总LE和无cvd的LE分别增加5.9(2.3-9.3)和5.3(3.0-7.6)年和6.1(0.8-10.6)和6.2(2.3-9.8)年。结论:改善生活方式对于减少心血管疾病相关的医疗负担和促进健康老龄化至关重要,特别是对于高遗传风险个体。
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来源期刊
Genome Medicine
Genome Medicine GENETICS & HEREDITY-
CiteScore
20.80
自引率
0.80%
发文量
128
审稿时长
6-12 weeks
期刊介绍: Genome Medicine is an open access journal that publishes outstanding research applying genetics, genomics, and multi-omics to understand, diagnose, and treat disease. Bridging basic science and clinical research, it covers areas such as cancer genomics, immuno-oncology, immunogenomics, infectious disease, microbiome, neurogenomics, systems medicine, clinical genomics, gene therapies, precision medicine, and clinical trials. The journal publishes original research, methods, software, and reviews to serve authors and promote broad interest and importance in the field.
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