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- Title
Meta-regression of genome-wide association studies to estimate age-varying genetic effects.
- Authors
Pagoni, Panagiota; Higgins, Julian P. T.; Lawlor, Deborah A.; Stergiakouli, Evie; Warrington, Nicole M.; Morris, Tim T.; Tilling, Kate
- Abstract
Fixed-effect meta-analysis has been used to summarize genetic effects on a phenotype across multiple Genome-Wide Association Studies (GWAS) assuming a common underlying genetic effect. Genetic effects may vary with age (or other characteristics), and not allowing for this in a GWAS might lead to bias. Meta-regression models between study heterogeneity and allows effect modification of the genetic effects to be explored. The aim of this study was to explore the use of meta-analysis and meta-regression for estimating age-varying genetic effects on phenotypes. With simulations we compared the performance of meta-regression to fixed-effect and random -effects meta-analyses in estimating (i) main genetic effects and (ii) age-varying genetic effects (SNP by age interactions) from multiple GWAS studies under a range of scenarios. We applied meta-regression on publicly available summary data to estimate the main and age-varying genetic effects of the FTO SNP rs9939609 on Body Mass Index (BMI). Fixed-effect and random-effects meta-analyses accurately estimated genetic effects when these did not change with age. Meta-regression accurately estimated both main genetic effects and age-varying genetic effects. When the number of studies or the age-diversity between studies was low, meta-regression had limited power. In the applied example, each additional minor allele (A) of rs9939609 was inversely associated with BMI at ages 0 to 3, and positively associated at ages 5.5 to 13. Our findings challenge the assumption that genetic effects are consistent across all ages and provide a method for exploring this. GWAS consortia should be encouraged to use meta-regression to explore age-varying genetic effects.
- Subjects
GENOME-wide association studies; FIXED effects model; BODY mass index; METAGENOMICS
- Publication
European Journal of Epidemiology, 2024, Vol 39, Issue 3, p257
- ISSN
0393-2990
- Publication type
Article
- DOI
10.1007/s10654-023-01086-1