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We systematically assessed genetic variation in the\n                      <jats:italic>GLP1R<\/jats:italic>\n                      locus for impact on mental ill\u2010health (MIH) and cardiometabolic phenotypes across diverse populations within UK Biobank.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>\n                      All genetic variants with minor allele frequency &gt;1% in the\n                      <jats:italic>GLP1R<\/jats:italic>\n                      locus were investigated for associations with MIH phenotypes and cardiometabolic phenotypes. Linear or Logistic regression analyses (adjusted for age, sex, population structure and genotyping chip) were conducted separately in unrelated individuals of self\u2010reported white British (\n                      <jats:italic>N<\/jats:italic>\n                      \u2009=\u2009408\u2009774), white European (\n                      <jats:italic>N<\/jats:italic>\n                      \u2009=\u200950\u2009314), South Asian (\n                      <jats:italic>N<\/jats:italic>\n                      \u2009=\u20097667), multiple\u2010ancestry groups (\n                      <jats:italic>N<\/jats:italic>\n                      \u2009=\u200910\u2009437) or African\u2010Caribbean (\n                      <jats:italic>N<\/jats:italic>\n                      \u2009=\u20097641) subsets. All ancestries were subsequently combined in an inverse variance\u2010weighted fixed effects meta\u2010analysis. Bonferroni correction for multiple testing was applied (for number of independent genetic variants).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Associations were identified between\n                      <jats:italic>GLP1R<\/jats:italic>\n                      variants and body mass index (BMI), blood pressure and type 2 diabetes in all ancestries. All ancestries except South Asian had significant MIH associations (mood instability: rs111265626\u2010G, odds ratio [OR] 0.851 [confidence interval, CI 0.79\u20130.92], risk\u2010taking behaviour: rs75408972\u2010T, OR 1.05 [CI 1.03\u20131.08] or chronic pain: rs9296280\u2010C, OR 0.645 [CI 0.54\u20130.78]). The trans\u2010ancestry meta\u2010analysis showed mainly consistent effect sizes and directions for metabolic traits, but discordant directions MIH associations. Only signals for chronic pain, stroke and BMI influenced expression of\n                      <jats:italic>GLP1R<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      <jats:italic>GLP1R<\/jats:italic>\n                      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\n                      <jats:italic>GLP1R<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.16178","type":"journal-article","created":{"date-parts":[[2025,1,22]],"date-time":"2025-01-22T03:01:32Z","timestamp":1737514892000},"page":"1845-1858","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Association of\n                    <scp>\n                      <i>GLP1R<\/i>\n                    <\/scp>\n                    locus with mental ill\u2010health endophenotypes and cardiometabolic traits: A trans\u2010ancestry study in\n                    <scp>UK<\/scp>\n                    Biobank"],"prefix":"10.1111","volume":"27","author":[{"given":"Madeleine M. 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