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

• Background: 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. Methods: 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. Findings: 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). Interpretation: 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. Funding: Klarman Family Foundation, US National Institute of Mental Health (NIMH). © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Hälsovetenskap -- Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Health Sciences -- Public Health, Global Health, Social Medicine and Epidemiology (hsv//eng)

Nyckelord

Diseases

Health risks

Records management

Risk assessment

Risk perception

Anorexia nervosa

Biobanks

Electronic health

Health records

Odd ratios

Risk score

Stable weight

Weight change

Weight gain

Weight loss

Trajectories

adult

biobank

electronic health record

genome-wide association study

human

multifactorial inheritance

procedures

Biological Specimen Banks

Body-Weight Trajectory

Electronic Health Records

Humans

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)