Mandla Ravi, Schroeder Philip, Porneala Bianca, Florez Jose C, Meigs James B, Mercader Josep M, Leong Aaron
medRxiv. 2023 Sep 10:2023.09.08.23295276. doi: 10.1101/2023.09.08.23295276.
The clinical utility of genetic information for type 2 diabetes (T2D) prediction with polygenic score (PGS) in ancestrally diverse, real-world US healthcare systems is unclear, especially for those at low clinical phenotypic risk for T2D.
We tested the association of PGS with T2D incidence in patients followed within a primary care practice network over 16 years in four hypothetical scenarios that varied by clinical data availability (N = 14,712): 1) age and sex, 2) age, sex, BMI, systolic blood pressure, and family history of diabetes; 3) all variables in (2) and random glucose; 4) all variables in (3), HDL, total cholesterol, and triglycerides, combined in a clinical risk score (CRS). To determine whether genetic effects differed by baseline clinical risk, we tested for interaction with the CRS.
PGS was associated with incident diabetes in all models. Adjusting for age and sex only, the Hazard Ratio (HR) per PGS standard deviation (SD) was 1.76 (95% CI 1.68, 1.84) and the HR of top 5% of PGS vs interquartile range (IQR) was 2.80 (2.39, 3.28). Adjusting for the CRS, the HR per SD was 1.48 (1.40, 1.57) and HR of top 5% of PGS vs IQR was 2.09 (1.72, 2.55). Genetic effects differed by baseline clinical risk [(PGS-CRS interaction =0.05; CRS below the median: HR 1.60 (1.43, 1.79); CRS above the median: HR 1.45 (1.35, 1.55)].
Genetic information can help identify high-risk patients even among those perceived to be low risk in a clinical evaluation.
在种族多样的美国现实医疗系统中，利用多基因分数（PGS）进行2型糖尿病（T2D）预测的遗传信息的临床实用性尚不清楚，尤其是对于那些T2D临床表型风险较低的患者。
我们在四个因临床数据可用性而异的假设场景中（N = 14,712），测试了PGS与在初级保健实践网络中随访16年的患者T2D发病率之间的关联：1）年龄和性别；2）年龄、性别、体重指数、收缩压和糖尿病家族史；3）（2）中的所有变量和随机血糖；4）（3）中的所有变量、高密度脂蛋白、总胆固醇和甘油三酯，合并为临床风险评分（CRS）。为了确定遗传效应是否因基线临床风险而异，我们测试了与CRS的相互作用。
在所有模型中，PGS均与糖尿病发病相关。仅调整年龄和性别时，每PGS标准差（SD）的风险比（HR）为1.76（95%CI 1.68, 1.84），PGS最高5%与四分位间距（IQR）的HR为2.80（2.39, 3.28）。调整CRS后，每SD的HR为1.48（1.40, 1.57），PGS最高5%与IQR的HR为2.09（1.72, 2.55）。遗传效应因基线临床风险而异[（PGS-CRS相互作用=0.05；CRS低于中位数：HR 1.60（1.43, 1.79）；CRS高于中位数：HR 1.45（1.35, 1.55）]。
即使在临床评估中被认为风险较低的患者中，遗传信息也有助于识别高危患者。
