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Sex differences in genetic and environmental influences on frailty and its relation to body mass index and education

By Jonathan K. L. Mak, Chandra A. Reynolds, Sara Hagg, Xia Li, Malin Ericsson, Nancy Pedersen, Juulia Jylhava, Ralf Kuja-Halkola

Posted 11 Dec 2020
medRxiv DOI: 10.1101/2020.12.08.20245969

Background: Frailty is a multifactorial expression of aging influenced by numerous genetic and environmental factors. However, sex differences in how these factors may affect frailty, and the gene-environment interplay among frailty and two of its well-established risk factors, unhealthy body mass index (BMI) and low education, are less clear. Methods: In a large sample of 42,994 Swedish twins aged 41-99 years, we used structural equation models to estimate the genetic (heritability) and environmental sources of variance in frailty, defined as the Rockwood frailty index (FI), separately in men and women. We also estimated the genetic and environmental contributions to the associations between FI and BMI, and FI and education. Moderation models were fitted to test for gene-environment interaction by levels of BMI and education. Results: Genetic and individual-specific environmental factors contributed approximately equally to the FI variance. The heritability of FI was slightly higher in women (52%) than in men (45%), yet we found only weak-to-no indication of different sources of genetic variance influencing frailty in men and women. A small-to-moderate genetic overlap between FI and BMI, and a perfect negative correlation of the environmental factors common to twins in a pair between FI and education were observed. Additionally, the heritability of FI was greater at both low and high BMI levels, with similar patterns of moderation in both sexes. Conclusions: Individual differences in frailty are equally influenced by genetic and individual-specific environmental factors, and different mechanisms seem to underlie the association of frailty with BMI and education.

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