AUTHOR=Cui Junhao , Fu Shuqin , Zhu Lin , Li Peng , Song Chunlan 

TITLE=Mendelian randomization shows causal effects of birth weight and childhood body mass index on the risk of frailty

JOURNAL=Frontiers in Public Health

VOLUME=Volume 12 - 2024

YEAR=2024

URL=https://www.frontiersin.org/journals/public-health/articles/10.3389/fpubh.2024.1270698

DOI=10.3389/fpubh.2024.1270698

ISSN=2296-2565

ABSTRACT=The association between birth weight and childhood body mass index (BMI) and frailty has been extensively studied, but it is currently unclear whether this relationship is causal.We utilized a two-sample Mendelian randomization (MR) methodology to investigate the causal effects of birth weight and childhood BMI on the risk of frailty. Instrumental variables strongly (P<5E-08) associated with own birth weight (N=298,142 infants), offspring birth weight (N=210,267 mothers), and childhood BMI (N=39,620) were identified from large-scale genomic data from genome-wide association studies (GWAS). Frailty status was assessed using the frailty index, which was obtained from comprehensive geriatric assessments of older adults within the UK Biobank and TwinGene database (N=175,226).Results: Genetically predicted one standard deviation (SD) increase in own birth weight, but not offspring birth weight (maternal-specific), was linked to a decreased frailty index (β per SD increase= -0.068, 95%CI = -0.106 to -0.030, P = 3.92E-04). Conversely, genetically predicted one SD increase in childhood BMI was associated with an elevated frailty index (β per SD increase= 0.080, 95%CI = 0.046 to 0.114, P = 3.43E-06) with good statistical power (99.8%). The findings remained consistent across sensitivity analyses and showed no horizontal pleiotropy (P>0.05).This MR study provides evidence supporting a causal 3 relationship between lower birth weight, higher childhood BMI, and increased frailty risk.