Using genetics to detangle the relationships between red cell distribution width and cardiovascular diseases: a unique role for body mass index.
Using genetics to detangle the relationships between red cell distribution width and cardiovascular diseases: a unique role for body mass index.
复制标题
DOI：
10.1136/openhrt-2021-001713
复制
发表时间：
2021-09
期刊：
影响因子：
2.7
通讯作者：
Wells QS
中科院分区：
文献类型：
--
作者：
Thayer TE;Huang S;Farber-Eger E;Beckman JA;Brittain EL;Mosley JD;Wells QS
红细胞分布宽度（RDW）是一个神秘的生物标志物，与多种心血管疾病（cvd）的存在和严重程度相关。目前尚不清楚RDW升高是否导致了心血管疾病，或者与心血管疾病有多效性关系。我们使用现代遗传技术来探索RDW、CVD和CVD危险因素之间的病因学关联证据。使用基于电子健康记录（EHR）的队列，我们为RDW建立并部署了遗传风险评分（GRS），以测试RDW和心血管现象之间的共享遗传结构。我们还创建了常见CVD（冠状动脉疾病、心力衰竭、心房颤动、外周动脉疾病、静脉血栓栓塞）和CVD危险因素（体重指数（BMI）、低密度脂蛋白、高密度脂蛋白、收缩压、舒张压、血清甘油三酯、肾小球滤过率估计值、糖尿病）的GRSs，以检测它们与RDW的相关性。通过双样本孟德尔随机化（MR）进一步研究显著的GRS关联。在一个单独的基于ehr的队列中，比较胃旁路手术前1年和胃旁路手术后1-2年的RDW值。在17937名受试者的队列中，RDW GRS和cvd之间没有显著关联。在心血管疾病和心血管疾病危险因素中，只有基因预测BMI与RDW相关。在随后的分析中，BMI通过多种MR方法与RDW相关。在接受减肥手术的受试者中，RDW在手术后下降，并与BMI变化呈线性关系。除BMI外，RDW不太可能是CVD或CVD危险因素的病因上游或下游。遗传和临床关联分析支持BMI和RDW之间的病因学关系。
Red cell distribution width (RDW) is an enigmatic biomarker associated with the presence and severity of multiple cardiovascular diseases (CVDs). It is unclear whether elevated RDW contributes to, results from, or is pleiotropically related to CVDs. We used contemporary genetic techniques to probe for evidence of aetiological associations between RDW, CVDs, and CVD risk factors. Using an electronic health record (EHR)-based cohort, we built and deployed a genetic risk score (GRS) for RDW to test for shared genetic architecture between RDW and the cardiovascular phenome. We also created GRSs for common CVDs (coronary artery disease, heart failure, atrial fibrillation, peripheral arterial disease, venous thromboembolism) and CVD risk factors (body mass index (BMI), low-density lipoprotein, high-density lipoprotein, systolic blood pressure, diastolic blood pressure, serum triglycerides, estimated glomerular filtration rate, diabetes mellitus) to test each for association with RDW. Significant GRS associations were further interrogated by two-sample Mendelian randomisation (MR). In a separate EHR-based cohort, RDW values from 1-year pre-gastric bypass surgery and 1–2 years post-gastric bypass surgery were compared. In a cohort of 17 937 subjects, there were no significant associations between the RDW GRS and CVDs. Of the CVDs and CVD risk factors, only genetically predicted BMI was associated with RDW. In subsequent analyses, BMI was associated with RDW by multiple MR methods. In subjects undergoing bariatric surgery, RDW decreased postsurgery and followed a linear relationship with BMI change. RDW is unlikely to be aetiologically upstream or downstream of CVDs or CVD risk factors except for BMI. Genetic and clinical association analyses support an aetiological relationship between BMI and RDW.
登录
查看更多内容
影响因子：
30.8
作者：
Das, Sayantan;Forer, Lukas;Schoenherr, Sebastian;Sidore, Carlo;Locke, Adam E.;Kwong, Alan;Vrieze, Scott I.;Chew, Emily Y.;Levy, Shawn;McGue, Matt;Schlessinger, David;Stambolian, Dwight;Loh, Po-Ru;Iacono, William G.;Swaroop, Anand;Scott, Laura J.;Cucca, Francesco;Kronenberg, Florian;Boehnke, Michael;Abecasis, Goncalo R.;Fuchsberger, Christian
通讯作者：
Fuchsberger, Christian
影响因子：
16.6
作者：
Xue A;Wu Y;Zhu Z;Zhang F;Kemper KE;Zheng Z;Yengo L;Lloyd-Jones LR;Sidorenko J;Wu Y;eQTLGen Consortium;McRae AF;Visscher PM;Zeng J;Yang J
通讯作者：
Yang J
影响因子：
3.8
作者：
Fujita, B.;Strodthoff, D.;Jung, C.
通讯作者：
Jung, C.
影响因子：
82.9
作者：
Klarin, Derek;Lynch, Julie;Damrauer, Scott M.
通讯作者：
Damrauer, Scott M.
影响因子：
2.9
作者：
Vargas-Ruiz, Angel G.;Hernandez-Rivera, Gabriela;Herrera, Miguel F.
通讯作者：
Herrera, Miguel F.