Highly elevated polygenic risk scores are better predictors of myocardial infarction risk early in life than later.
Highly elevated polygenic risk scores are better predictors of myocardial infarction risk early in life than later.
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DOI：
10.1186/s13073-021-00828-8
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发表时间：
2021-01-28
期刊：
影响因子：
12.3
通讯作者：
Gibson G
中科院分区：
文献类型：
--
作者：
Isgut M;Sun J;Quyyumi AA;Gibson G
目前已有几种多基因风险评分（PRS）用于心血管疾病风险预测，但将多基因风险评分与传统危险因素结合起来进行风险预测的附加价值尚存疑问。本研究评估了包括194、46K、1.5M和6M snp产生的4个PRS以及常规危险因素在内的临床应用，以预测缺血性心脏病（IHD）、心肌梗死（MI）和50岁或50岁之前的首次心肌梗死事件（早期心肌梗死）的风险。交叉验证的逻辑回归（LR）算法对来自英国生物银行（UKB）的约440K欧洲血统个体或整个UKB人群进行了训练，包括传统的出生时确定的风险因素（血统、性别）和个体一生中不固定的风险因素（年龄、BMI、高血压、高脂血症、糖尿病、吸烟、家族史）的不同组合，包括和不包括PRS。算法分别以IHD、MI和早期MI作为预测标签进行训练。当使用出生时确定的危险因素对LR进行训练时，添加四种PRS显著改善了IHD（0.62至0.67）和MI（0.67至0.73）以及早期MI（0.70至0.79）的曲线下面积（AUC）。当使用所有危险因素训练LR时，添加4个PRS仅导致IHD和MI评分的第98和99百分位数的疾病患病率显着升高。当无法获得晚年危险因素的知识时，PRS改善了生命早期的心血管危险分层。然而，到了中年，当许多危险因素已知时，PRS的改善对一般人群来说是边际的。在线版本包含补充材料，可在10.1186/s13073-021-00828-8获得。
Several polygenic risk scores (PRS) have been developed for cardiovascular risk prediction, but the additive value of including PRS together with conventional risk factors for risk prediction is questionable. This study assesses the clinical utility of including four PRS generated from 194, 46K, 1.5M, and 6M SNPs, along with conventional risk factors, to predict risk of ischemic heart disease (IHD), myocardial infarction (MI), and first MI event on or before age 50 (early MI). A cross-validated logistic regression (LR) algorithm was trained either on ~ 440K European ancestry individuals from the UK Biobank (UKB), or the full UKB population, including as features different combinations of conventional established-at-birth risk factors (ancestry, sex) and risk factors that are non-fixed over an individual’s lifespan (age, BMI, hypertension, hyperlipidemia, diabetes, smoking, family history), with and without also including PRS. The algorithm was trained separately with IHD, MI, and early MI as prediction labels. When LR was trained using risk factors established-at-birth, adding the four PRS significantly improved the area under the curve (AUC) for IHD (0.62 to 0.67) and MI (0.67 to 0.73), as well as for early MI (0.70 to 0.79). When LR was trained using all risk factors, adding the four PRS only resulted in a significantly higher disease prevalence in the 98th and 99th percentiles of both the IHD and MI scores. PRS improve cardiovascular risk stratification early in life when knowledge of later-life risk factors is unavailable. However, by middle age, when many risk factors are known, the improvement attributed to PRS is marginal for the general population. The online version contains supplementary material available at 10.1186/s13073-021-00828-8.
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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
克罗恩病和溃疡性结肠炎表型的遗传决定因素：遗传关联研究。
DOI：
10.1016/s0140-6736(15)00465-1
发表时间：
2016-01-09
期刊：
Lancet (London, England)
影响因子：
--
作者：
Cleynen I;Boucher G;Jostins L;Schumm LP;Zeissig S;Ahmad T;Andersen V;Andrews JM;Annese V;Brand S;Brant SR;Cho JH;Daly MJ;Dubinsky M;Duerr RH;Ferguson LR;Franke A;Gearry RB;Goyette P;Hakonarson H;Halfvarson J;Hov JR;Huang H;Kennedy NA;Kupcinskas L;Lawrance IC;Lee JC;Satsangi J;Schreiber S;Théâtre E;van der Meulen-de Jong AE;Weersma RK;Wilson DC;International Inflammatory Bowel Disease Genetics Consortium;Parkes M;Vermeire S;Rioux JD;Mansfield J;Silverberg MS;Radford-Smith G;McGovern DP;Barrett JC;Lees CW
通讯作者：
Lees CW
影响因子：
5
作者：
Fry A;Littlejohns TJ;Sudlow C;Doherty N;Adamska L;Sprosen T;Collins R;Allen NE
通讯作者：
Allen NE
影响因子：
9.2
作者：
Chang CC;Chow CC;Tellier LC;Vattikuti S;Purcell SM;Lee JJ
通讯作者：
Lee JJ
影响因子：
16.6
作者：
Duncan, L.;Shen, H.;Domingue, B.
通讯作者：
Domingue, B.