Exploring the clinical and genetic associations of adult weight trajectories using electronic health records in a racially diverse biobank: a phenome-wide and polygenic risk study.
Exploring the clinical and genetic associations of adult weight trajectories using electronic health records in a racially diverse biobank: a phenome-wide and polygenic risk study.
复制标题
DOI：
10.1016/s2589-7500(22)00099-1
复制
发表时间：
2022-08
影响因子：
30.8
通讯作者：
Huckins, Laura M.
中科院分区：
文献类型：
--
作者：
Xu, Jiayi;Johnson, Jessica S.;Signer, Rebecca;Birgegard, Andreas;Jordan, Jennifer;Kennedy, Martin A.;Landen, Mikael;Maguire, Sarah L.;Martin, Nicholas G.;Mortensen, Preben Bo;Petersen, Liselotte, V;Thornton, Laura M.;Bulik, Cynthia M.;Huckins, Laura M.
体重轨迹可能反映个人健康状况。在这项研究中，我们的目的是使用BioMe Biobank中的电子健康记录（EHR）检查成人体重轨迹的临床和遗传关联。我们使用EHR中的年度体重（稳定体重、体重增加、体重减轻和体重周期），基于体重变化（5%或10%）的先验定义构建了四个体重轨迹;最终的体重数据集包括21487名参与者，每年测量162783次体重。为了确认体重轨迹的准确分配，我们手动查看了100个随机个体的体重轨迹图。然后，我们进行了一项无假设的全表型关联研究（PheWAS），以确定与每个体重轨迹相关的疾病。接下来，我们使用GCTA-GREML估计了体重轨迹的单核苷酸多态性遗传力（hSNP2），并对这些体重轨迹进行了神经性厌食症和抑郁症多基因风险评分（PRS）的假设驱动分析，因为这两种疾病都与体重变化有关。我们将我们的分析扩展到英国生物银行，以将患者人群的结果复制到一般健康人群。我们发现手动分配的权重轨迹与算法分配的权重轨迹之间具有高度一致性（准确度≥ 98%）。在我们的PheWAS中，体重稳定与通过Bonferroni校正p值的患者的疾病风险降低一致相关（p ≤ 4.4 × 10 − 5）。此外，我们确定了抑郁症与体重周期之间的关联（比值比[OR] 1.42，95%CI 1.31 - 1.55，p ≤ 7.7 × 10 − 16）。成年体重轨迹是可遗传的（使用5%体重变化作为截止值：hSNP 2为2.1%，95% CI 0.9 - 3.3，用于稳定体重; 4.1%，1.4 - 6.8，用于体重增加; 5.5%，2.8 - 8.2，用于体重减轻;以及4.7%，2.3 - 7.1%，用于体重周期）。在无进食障碍诊断的个体中，神经性厌食症PRS与体重减轻轨迹呈正相关（OR 1 SD 1.16，95% CI 1.07 - 1.26，每1 SD更高的PRS，p = 0.011），肥胖PRS不会减弱这种关联。排列测试后，没有发现抑郁PRS和体重轨迹之间的关联。所有主要发现均在英国生物样本库中重复（p <0.05）。我们的研究结果表明，从纵向角度考虑体重与健康的关系非常重要，并强调了体重管理在疾病发展和进展中的关键作用。卡拉曼家庭基金会，美国国家精神卫生研究所（NIMH）。
Weight trajectories might reflect individual health status. In this study, we aimed to examine the clinical and genetic associations of adult weight trajectories using electronic health records (EHRs) in the BioMe Biobank. We constructed four weight trajectories based on a-priori definitions of weight changes (5% or 10%) using annual weight in EHRs (stable weight, weight gain, weight loss, and weight cycle); the final weight dataset included 21 487 participants with 162 783 annual weight measures. To confirm accurate assignment of weight trajectories, we manually reviewed weight trajectory plots for 100 random individuals. We then did a hypothesis-free phenome-wide association study (PheWAS) to identify diseases associated with each weight trajectory. Next, we estimated the single-nucleotide polymorphism-based heritability (hSNP2) of weight trajectories using GCTA-GREML, and we did a hypothesis-driven analysis of anorexia nervosa and depression polygenic risk scores (PRS) on these weight trajectories, given both diseases are associated with weight changes. We extended our analyses to the UK Biobank to replicate findings from a patient population to a generally healthy population. We found high concordance between manually assigned weight trajectories and those assigned by the algorithm (accuracy ≥98%). Stable weight was consistently associated with lower disease risks among those passing Bonferroni-corrected p value in our PheWAS (p≤4·4 × 10−5). Additionally, we identified an association between depression and weight cycle (odds ratio [OR] 1·42, 95% CI 1·31–1·55, p≤7·7 × 10−16). The adult weight trajectories were heritable (using 5% weight change as the cutoff: hSNP2 of 2·1%, 95% CI 0·9–3·3, for stable weight; 4·1%, 1·4–6·8, for weight gain; 5·5%, 2·8–8·2, for weight loss; and 4·7%, 2·3–7·1%, for weight cycle). Anorexia nervosa PRS was positively associated with weight loss trajectory among individuals without eating disorder diagnoses (OR1SD 1·16, 95% CI 1·07–1·26, per 1 SD higher PRS, p=0·011), and the association was not attenuated by obesity PRS. No association was found between depression PRS and weight trajectories after permutation tests. All main findings were replicated in the UK Biobank (p<0·05). Our findings suggest the importance of considering weight from a longitudinal aspect for its association with health and highlight a crucial role of weight management during disease development and progression. Klarman Family Foundation, US National Institute of Mental Health (NIMH).