Association of GLP1R locus with mental ill‐health endophenotypes and cardiometabolic traits: A trans‐ancestry study in UK Biobank
Authors' conclusion
GLP1R variants have consistent cardiometabolic effects across ancestries, but effects on MIH phenotypes are more varied. Any observed behavioural changes with GLP1RA are likely not acting directly through GLP1R.
Study context
- Population
- Unrelated UK Biobank individuals of diverse self-reported ancestries; GLP1R locus variants with minor allele frequency >1%
- Participants
- 408,774 / 50,314 / 7,667 / 10,437 / 7,641
- Comparison
- White British vs White European vs South Asian vs Multiple-ancestry vs African-Caribbean
- White Britishn = 408,774
- White Europeann = 50,314
- South Asiann = 7,667
- Multiple-ancestryn = 10,437
- African-Caribbeann = 7,641
- Outcome
- Associations of GLP1R variants with mental ill-health (MIH) and cardiometabolic phenotypes
Methodological detailstrans-ancestry, inverse variance-weighted fixed effects meta-analysis, Bonferroni correction
- Trans-ancestry
- Inverse variance-weighted fixed effects meta-analysis
- Bonferroni correction
Pooled result
As reported in the abstract
Mood instability: rs111265626-G, OR
0.851 (0.79-0.92) (CI)
Risk-taking behaviour: rs75408972-T, OR
1.05 (1.03-1.08) (CI)
Chronic pain: rs9296280-C, OR
0.645 (0.54-0.78) (CI)
Further pooled results
Trans-ancestry meta-analysis
- Mainly consistent effect sizes and directions for metabolic traits, but discordant directions for mental ill-health (MIH) associations
GLP1R expression
- Only signals for chronic pain, stroke and body mass index (BMI) influenced GLP1R expression
Original publication
Association of GLP1R locus with mental ill‐health endophenotypes and cardiometabolic traits: A trans‐ancestry study in UK Biobank. Diabetes Obes Metab. Published 22 January 2025. doi:10.
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