Division of Blood Disorders and Public Health Genomics National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention Atlanta GA USA.
Division of General Internal Medicine, Massachusetts General Hospital Boston MA USA.
J Am Heart Assoc. 2023 Nov 21;12(22):e030779. doi: 10.1161/JAHA.123.030779. Epub 2023 Nov 10.
Family history reflects the complex interplay of genetic susceptibility and shared environmental exposures and is an important risk factor for obesity, diabetes, and heart and blood conditions (ODHB). However, the overlap in family history associations between various ODHBs has not been quantified.
We assessed the association between a self-reported family history of ODHBs and their risk in the adult population (age ≥20 years) of the AoU (All of Us) Research Program, a longitudinal cohort study of diverse participants across the United States. We conducted a family history-wide association study to systematically assess the association of a first-degree family history of 15 ODHBs in AoU. We performed stratified analyses based on racial and ethnic categories, education, household income and gender minority status, and quantified associations by type of affected relatives. Of 125 430 participants, 76.8% reported a first-degree family history of any ODHB, most commonly hypertension (n=64 982, 51.8%), high cholesterol (49 753, 39.7%), and heart attack (29 618, 23.6%). We use the FamWAS method to estimate 225 familial associations among 15 ODHBs. The results include overlapping associations between family history of different types of cardiometabolic conditions (such as type 2 diabetes and coronary artery disease), and their risk factors (obesity, hypertension), where adults with a family history of 1 ODHB exhibited 1.1 to 5.6 times (1.5, on average) the odds of having a different ODHB.
Our findings inform the utility of family history data as a risk assessment and screening tool for the prevention of ODHBs and to provide additional insights into shared risk factors and pathogenic mechanisms.
家族史反映了遗传易感性和共同环境暴露的复杂相互作用，是肥胖、糖尿病以及心脏和血液疾病（ODHB）的重要危险因素。然而，各种 ODHB 之间家族史关联的重叠尚未被量化。
我们评估了在 AoU（All of Us）研究计划的成年人群（年龄≥20 岁）中，自我报告的 ODHB 家族史与其风险之间的关联，该计划是一项针对美国各地不同参与者的纵向队列研究。我们进行了一项家族史全关联研究，以系统评估 AoU 中 15 种 ODHB 的一级亲属家族史关联。我们根据种族和族裔类别、教育程度、家庭收入和性别少数群体状况进行分层分析，并按受影响亲属的类型量化关联。在 125430 名参与者中，76.8%报告了任何 ODHB 的一级亲属家族史，最常见的是高血压（n=64982，51.8%）、高胆固醇（49753，39.7%）和心脏病发作（29618，23.6%）。我们使用 FamWAS 方法估计了 15 种 ODHB 之间的 225 种家族关联。结果包括不同类型的心血管理论条件（如 2 型糖尿病和冠状动脉疾病）及其危险因素（肥胖、高血压）之间的家族史重叠关联，一级亲属中有 1 种 ODHB 的成年人患不同 ODHB 的几率是 1.1 到 5.6 倍（平均为 1.5 倍）。
我们的研究结果为利用家族史数据作为预防 ODHB 的风险评估和筛查工具提供了信息，并为共同的危险因素和发病机制提供了额外的见解。
