German Center for Neurodegenerative diseases (DZNE), Population Health Sciences, Sigmund-Freud-Strasse 27, 53127 Bonn, Germany.
Department of Clinical Neurosciences, Stroke Research Group, University of Cambridge, UK.
BMJ. 2018 Oct 24;363:k4168. doi: 10.1136/bmj.k4168.
To evaluate the associations of a polygenic risk score and healthy lifestyle with incident stroke.
Prospective population based cohort study.
UK Biobank Study, UK.
306 473 men and women, aged 40-73 years, recruited between 2006 and 2010.
Hazard ratios for a first stroke, estimated using Cox regression. A polygenic risk score of 90 single nucleotide polymorphisms previously associated with stroke was constructed at P<1×10 to test for an association with incident stroke. Adherence to a healthy lifestyle was determined on the basis of four factors: non-smoker, healthy diet, body mass index <30 kg/m, and regular physical exercise.
During a median follow-up of 7.1 years (2 138 443 person years), 2077 incident strokes (1541 ischaemic stroke, 287 intracerebral haemorrhage, and 249 subarachnoid haemorrhage) were ascertained. The risk of incident stroke was 35% higher among those at high genetic risk (top third of polygenic score) compared with those at low genetic risk (bottom third): hazard ratio 1.35 (95% confidence interval 1.21 to 1.50), P=3.9×10. Unfavourable lifestyle (0 or 1 healthy lifestyle factors) was associated with a 66% increased risk of stroke compared with a favourable lifestyle (3 or 4 healthy lifestyle factors): 1.66 (1.45 to 1.89), P=1.19×10. The association with lifestyle was independent of genetic risk stratums.
In this cohort study, genetic and lifestyle factors were independently associated with incident stroke. These results emphasise the benefit of entire populations adhering to a healthy lifestyle, independent of genetic risk.
评估多基因风险评分与健康生活方式与卒中发病的相关性。
前瞻性人群队列研究。
英国生物银行研究，英国。
306473 名年龄在 40-73 岁之间的男性和女性，于 2006 年至 2010 年期间招募。
使用 Cox 回归估计首次卒中的风险比。构建了一个与卒中相关的 90 个单核苷酸多态性的多基因风险评分（P<1×10），以检验其与卒中发病的相关性。健康生活方式的依从性是基于四个因素来确定的：不吸烟、健康饮食、身体质量指数<30kg/m2 和定期体育锻炼。
在中位随访 7.1 年（2138443 人年）期间，共确定了 2077 例卒中事件（1541 例缺血性卒中、287 例颅内出血和 249 例蛛网膜下腔出血）。与低遗传风险（多基因评分的底部三分之一）相比，高遗传风险（多基因评分的顶部三分之一）的卒中发病风险高出 35%：风险比为 1.35（95%置信区间为 1.21 至 1.50），P=3.9×10。与有利的生活方式（3 或 4 个健康生活方式因素）相比，不良的生活方式（0 或 1 个健康生活方式因素）与卒中发病风险增加 66%相关：1.66（1.45 至 1.89），P=1.19×10。这种与生活方式的相关性独立于遗传风险分层。
在这项队列研究中，遗传和生活方式因素与卒中发病独立相关。这些结果强调了整个人群遵循健康生活方式的益处，而与遗传风险无关。
