Impact of polygenic risk score for triglyceride trajectory and diabetic complications in subjects with type 2 diabetes based on large electronic medical record data from Taiwan: a case control study.

IF 5.4 2区 医学 Q1 Medicine
W-L Liao, Y-C Huang, Y-W Chang, C-F Cheng, T-Y Liu, H-F Lu, H-L Chen, F-J Tsai
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Abstract

Background: The prevalence of diabetic dyslipidemia has gradually increased worldwide and individuals with hypertriglyceridemia often have a high polygenic burden of triglyceride (TG)-increasing variants. However, the contribution of genetic variants to dyslipidemia in patients with type 2 diabetes (T2D) remains limited. Therefore, in this study, we aimed to investigate the genetic characteristics of longitudinal changes in TG levels among patients with T2D and summarize the genetic effects of polygenic risk score (PRS) on TG trajectory and risk of diabetic complications.

Methods: We conducted a case-control study. A total of 11,312 patients with T2D with longitudinal TG and genetic data were identified from a large hospital database in Taiwan. We then performed a genome-wide association study and calculated the relative PRS.

Results: In total, 21 single-nucleotide polymorphisms (SNPs) related to TG trajectory were identified and yielded an area under the receiver operating characteristic curve (ROC) of 0.712 for high TG trajectory risk among Taiwanese patients with T2D. A cumulative genetic effect was observed for high TG trajectory, even when considering the adherence of a lipid-lowering agent in stratified analysis. An increased PRS increases high TG trajectory risk in a logistic regression model (odds ratio = 1.55; 95% confidence interval [CI] = 1.31-1.83 in the validation cohort). The TG-specific PRS was associated with the risk of diabetic microvascular complications, including diabetic retinopathy and nephropathy (with hazard ratios of 1.11 [95% CI = 1.01-1.21, P = 0.027] and 1.05 [95% CI = 1.01-1.1, P = 0.018], respectively).

Conclusions: This study may contribute to the identification of patients with T2D who are at risk of abnormal TG levels and diabetic microvascular complications using polygenic information.

Abstract Image

基于台湾大型电子病历数据的多基因风险评分对 2 型糖尿病患者甘油三酯轨迹和糖尿病并发症的影响:一项病例对照研究。
背景:全世界糖尿病血脂异常的发病率逐渐升高,高甘油三酯血症患者通常具有较高的甘油三酯(TG)增加变异的多基因负担。然而,遗传变异对 2 型糖尿病(T2D)患者血脂异常的影响仍然有限。因此,在本研究中,我们旨在调查 T2D 患者 TG 水平纵向变化的遗传特征,并总结多基因风险评分(PRS)对 TG 变化轨迹和糖尿病并发症风险的遗传效应:我们进行了一项病例对照研究。方法:我们进行了一项病例对照研究,从台湾的一个大型医院数据库中找到了具有纵向血糖和遗传数据的 11,312 名 T2D 患者。然后,我们进行了全基因组关联研究,并计算了相对 PRS:结果:共鉴定出 21 个与 TG 轨迹相关的单核苷酸多态性(SNPs),并得出台湾 T2D 患者的高 TG 轨迹风险接收者操作特征曲线下面积(ROC)为 0.712。即使在分层分析中考虑到降脂药物的依从性,也能观察到高 TG 轨迹的累积遗传效应。在逻辑回归模型中,PRS 增加会增加高 TG 轨迹风险(验证队列中的几率比 = 1.55;95% 置信区间 [CI] = 1.31-1.83)。TG特异性PRS与糖尿病微血管并发症(包括糖尿病视网膜病变和肾病)的风险相关(危险比分别为1.11 [95% CI = 1.01-1.21, P = 0.027]和1.05 [95% CI = 1.01-1.1, P = 0.018]):这项研究有助于利用多基因信息识别TG水平异常和糖尿病微血管并发症风险的T2D患者。
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来源期刊
Journal of Endocrinological Investigation
Journal of Endocrinological Investigation ENDOCRINOLOGY & METABOLISM-
CiteScore
8.10
自引率
7.40%
发文量
242
期刊介绍: The Journal of Endocrinological Investigation is a well-established, e-only endocrine journal founded 36 years ago in 1978. It is the official journal of the Italian Society of Endocrinology (SIE), established in 1964. Other Italian societies in the endocrinology and metabolism field are affiliated to the journal: Italian Society of Andrology and Sexual Medicine, Italian Society of Obesity, Italian Society of Pediatric Endocrinology and Diabetology, Clinical Endocrinologists’ Association, Thyroid Association, Endocrine Surgical Units Association, Italian Society of Pharmacology.
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