Analysis of Clinical Traits Associated With Cardiovascular Health, Genomic Profiles, and Neuroimaging Markers of Brain Health in Adults Without Stroke or Dementia.
Analysis of Clinical Traits Associated With Cardiovascular Health, Genomic Profiles, and Neuroimaging Markers of Brain Health in Adults Without Stroke or Dementia.
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DOI：
10.1001/jamanetworkopen.2022.15328
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发表时间：
2022-05-02
影响因子：
13.8
通讯作者：
Falcone, Guido J.
中科院分区：
文献类型：
--
作者：
Acosta, Julian N.;Both, Cameron P.;Rivier, Cyprien;Szejko, Natalia;Leasure, Audrey C.;Gill, Thomas M.;Payabvash, Seyedmehdi;Sheth, Kevin N.;Falcone, Guido J.
在没有中风或痴呆症的人中，观察和基因组美国心脏协会生活的简单7分与大脑健康的脑成像标记物相关吗？这项对35名来自英国生物库研究的 914参与者的遗传关联研究发现，更好地观察生命的简单7个轮廓与较低的白质高强度体积和较高的脑体积相关，而更好的基因组生命的简单7个轮廓与较低的白质高强度体积相关。这些发现表明，心血管健康优化，以生活的简单7分衡量，与改善无症状患者的大脑健康有关。这项遗传关联研究评估了观察到的和遗传的心血管健康状况与无症状成年人大脑健康的相关性。美国心脏协会(AHA)的生活简单7分(LS7)包含了7个与促进心血管健康相关的生物学和生活方式因素。为了测试更健康的LS7图谱是否与没有中风或痴呆症的人的大脑健康显著相关，并评估基因组信息是否可以概括观察到的LS7。这项遗传关联研究是英国生物库中嵌套的神经成像研究，英国生物库是英国一项基于人群的大型队列研究。2006年3月至2010年10月，英国生物库招募了502名 480名年龄在40岁至69岁之间的社区居民。这项研究集中在35名没有中风或痴呆症的 914参与者中，他们完成了脑磁共振成像研究，并拥有可用的全基因组数据。所有分析都是在2021年3月至2022年3月之间进行的。LS7(血压、低密度脂蛋白胆固醇、血红蛋白A1c、吸烟、锻炼、饮食和体重指数)的特征被临床和基因组学确定。评估了已知的影响LS7中包含的每一个特征的独立遗传变异。LS7的总分从0(最差)到14(最好)不等，分为差(≤4)、一般(>；4到9)和最佳(>；9)。感兴趣的结果是脑健康的两个神经成像标志物：白质高密度(WMH)体积和脑体积(BV)。最终的分析样本包括35名 914名参与者(平均年龄64.1[7.6]岁；18名 830[52.4%]女性)。对于WMH，与观察LS7轮廓较差的人相比，具有平均轮廓的人的平均体积低16%(β = −0.18；SE，0.03；P <； .001)，而具有最佳轮廓的人的平均体积低39%(β = −0.39；SE，0.03；P <； .001)。使用WMH的基因组LS7也得到了类似的结果(平均LS7图谱：β = −0.06；SE，0.014；P <； .001；最佳LS7图谱：β = −0.08；SE，0.018；P <； .001)。对于BV，与观察较差的LS7剖面的人相比，LS7剖面平均的人的容积增加0.55%(β = 0.09；SE，0.02；P <； .001)，而LS7剖面最优的人的容积增加1.9%(β = 0.14；SE，0.02；P <； .001)。基因组LS7谱与BV无关联。这些发现表明，在没有中风或痴呆症的人中，更健康的LS7特征与2个脑部健康的神经成像标志物的特征更好相关，这表明心血管健康的优化与无症状的人的大脑健康的改善有关。基因组信息恰当地概括了其中的一个关联，证实了对LS7进行基因组建模的可行性，并指出遗传易感性在观察到的心脏代谢和生活方式因素与大脑健康之间的关联中发挥了重要作用。
Are observed and genomic American Heart Association Life’s Simple 7 scores associated with brain imaging markers of brain health in persons without stroke or dementia? This genetic association study among 35 914 participants from the UK Biobank study found that better observed Life’s Simple 7 profiles were associated with lower white matter hyperintensity volume and higher brain volume and better genomic Life’s Simple 7 profiles were associated with lower white matter hyperintensity volumes. These findings suggest that cardiovascular health optimization, as measured by Life’s Simply 7 score, was associated with improved brain health in asymptomatic persons. This genetic association study assesses the associations of observed and genetic cardiovascular health profiles with brain health among asymptomatic adults. The American Heart Association (AHA) Life’s Simple 7 (LS7) score captures 7 biological and lifestyle factors associated with promoting cardiovascular health. To test whether healthier LS7 profiles are associated with significant brain health benefits in persons without stroke or dementia, and to evaluate whether genomic information can recapitulate the observed LS7. This genetic association study was a nested neuroimaging study within the UK Biobank, a large population-based cohort study in the United Kingdom. Between March 2006 and October 2010, the UK Biobank enrolled 502 480 community-dwelling persons aged 40 to 69 years at recruitment. This study focused on a subset of 35 914 participants without stroke or dementia who completed research brain magnetic resonance imaging (MRI) and had available genome-wide data. All analyses were conducted between March 2021 and March 2022. The LS7 (blood pressure, low-density lipoprotein cholesterol, hemoglobin A1c, smoking, exercise, diet, and body mass index) profiles were ascertained clinically and genomically. Independent genetic variants known to influence each of the traits included in the LS7 were assessed. The total LS7 score ranges from 0 (worst) to 14 (best) and was categorized as poor (≤4), average (>4 to 9) and optimal (>9). The outcomes of interest were 2 neuroimaging markers of brain health: white matter hyperintensity (WMH) volume and brain volume (BV). The final analytical sample included 35 914 participants (mean [SD] age 64.1 [7.6] years; 18 830 [52.4%] women). For WMH, compared with persons with poor observed LS7 profiles, those with average profiles had 16% (β = −0.18; SE, 0.03; P < .001) lower mean volume and those with optimal profiles had 39% (β = −0.39; SE, 0.03; P < .001) lower mean volume. Similar results were obtained using the genomic LS7 for WMH (average LS7 profile: β = −0.06; SE, 0.014; P < .001; optimal LS7 profile: β = −0.08; SE, 0.018; P < .001). For BV, compared with persons with poor observed LS7 profiles, those with average LS7 profiles had 0.55% (β = 0.09; SE, 0.02; P < .001) higher volume, and those with optimal LS7 profiles had 1.9% (β = 0.14; SE, 0.02; P < .001) higher volume. The genomic LS7 profiles were not associated with BV. These findings suggest that healthier LS7 profiles were associated with better profiles of 2 neuroimaging markers of brain health in persons without stroke or dementia, indicating that cardiovascular health optimization was associated with improved brain health in asymptomatic persons. Genomic information appropriately recapitulated 1 of these associations, confirming the feasibility of modeling the LS7 genomically and pointing to an important role of genetic predisposition in the observed association among cardiometabolic and lifestyle factors and brain health.
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DOI：
10.1136/bmj.c3666
发表时间：
2010-07-26
期刊：
BMJ (Clinical research ed.)
影响因子：
--
作者：
Debette S;Markus HS
通讯作者：
Markus HS
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
影响因子：
4.8
作者：
Battaglini, Marco;Jenkinson, Mark;De Stefano, Nicola
通讯作者：
De Stefano, Nicola
影响因子：
14.8
作者：
Choi SW;Mak TS;O'Reilly PF
通讯作者：
O'Reilly PF
影响因子：
13.6
作者：
Wilkinson, Tim;Schnier, Christian;Sudlow, Cathie L. M.
通讯作者：
Sudlow, Cathie L. M.