Department of Epidemiology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, P.O. Box 30.001 (FA40), 9700RB, Groningen, The Netherlands.
Department of Biomedical Sciences, Faculty of Medicine, Universitas Padjadjaran, Bandung, Indonesia.
Cardiovasc Diabetol. 2023 Oct 21;22(1):282. doi: 10.1186/s12933-023-02017-w.
It is unclear to what extent genetics explain the familial clustering and the co-occurrence of distinct cardiometabolic disorders in the general population. We therefore aimed to quantify the familial (co-)aggregation of various cardiometabolic disorders and to estimate the heritability of cardiometabolic traits and their genetic correlations using the large, multi-generational Lifelines Cohort Study.
We used baseline data of 162,416 participants from Lifelines. Cardiometabolic disorders including type 2 diabetes (T2D), cardiovascular diseases, hypertension, obesity, hypercholesterolemia, and metabolic syndrome (MetS), were defined in adult participants. Fifteen additional cardiometabolic traits indexing obesity, blood pressure, inflammation, glucose regulation, and lipid levels were measured in all included participants. Recurrence risk ratios (λ) for first-degree relatives (FDR) indexed familial (co-)aggregation of cardiometabolic disorders using modified conditional Cox proportional hazards models and were compared to those of spouses. Heritability (h), shared environment, and genetic correlation (r) were estimated using restricted maximum likelihood variance decomposition methods, adjusted for age, age, and sex.
Individuals with a first-degree relative with a cardiometabolic disorder had a higher risk of the same disorder, ranging from λ of 1.23 (95% CI 1.20-1.25) for hypertension to λ of 2.48 (95% CI 2.15-2.86) for T2D. Most of these were higher than in spouses (λ < λ), except for obesity which was slightly higher in spouses. We found moderate heritability for cardiometabolic traits (from h: 0.26 to h: 0.50). Cardiometabolic disorders showed positive familial co-aggregation, particularly between T2D, MetS, and obesity (from λ: 1.28 (95% CI 1.24-1.32) to λ: 1.61 (95% CI 1.52-1.70)), consistent with the genetic correlations between continuous intermediate traits (ranging from r: - 0.53 to r: 0.94).
There is positive familial (co-)aggregation of cardiometabolic disorder, moderate heritability of intermediate traits, and moderate genetic correlations between traits. These results indicate that shared genetics and common genetic architecture contribute to cardiometabolic disease.
遗传因素在多大程度上解释了普通人群中心血管代谢紊乱的家族聚集和同时发生尚不清楚。因此，我们旨在通过大型多代 Lifelines 队列研究，量化各种心血管代谢紊乱的家族（共同）聚集，并估计心血管代谢特征及其遗传相关性的遗传性。
我们使用 Lifelines 中 162,416 名参与者的基线数据。心血管代谢疾病包括 2 型糖尿病（T2D）、心血管疾病、高血压、肥胖、高胆固醇血症和代谢综合征（MetS），在成年参与者中定义。在所有纳入的参与者中还测量了 15 个额外的心血管代谢特征，用于索引肥胖、血压、炎症、葡萄糖调节和血脂水平。使用改良的条件 Cox 比例风险模型，通过一级亲属（FDR）的复发风险比（λ）来索引心血管代谢疾病的家族（共同）聚集，并与配偶进行比较。使用受限最大似然方差分解方法，根据年龄、年龄和性别调整，估计遗传率（h）、共享环境和遗传相关性（r）。
有心血管代谢疾病一级亲属的个体患同种疾病的风险更高，范围从高血压的 λ 为 1.23（95%CI 1.20-1.25）到 T2D 的 λ 为 2.48（95%CI 2.15-2.86）。除肥胖症外，大多数都高于配偶（λ < λ），肥胖症在配偶中略高。我们发现心血管代谢特征具有中度遗传性（从 h：0.26 到 h：0.50）。心血管代谢疾病表现出阳性家族共聚集，特别是 2 型糖尿病、代谢综合征和肥胖症之间（从 λ：1.28（95%CI 1.24-1.32）到 λ：1.61（95%CI 1.52-1.70）），与连续中间特征之间的遗传相关性一致（r 范围从 r：-0.53 到 r：0.94）。
心血管代谢紊乱存在阳性家族（共同）聚集，中间特征具有中度遗传性，特征之间具有中度遗传相关性。这些结果表明，共享遗传和共同遗传结构有助于心血管代谢疾病。
