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It is caused by lack of breathing during sleep, typically mediated by obstruction of airways or less frequently by misdirected central signals for breathing. The primary risk factor is a high body mass index, causing airway obstruction. However, understanding risk factors for sleep apnoea in non-obese (body mass index &lt;30\u2005kg\u00b7m<jats:sup>\u22122<\/jats:sup>) individuals requires further exploration. Our goal was to elucidate genetic risk factors for sleep apnoea in non-obese individuals.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We performed genome-wide association testing in non-obese individuals in FinnGen, including 20\u2009413 participants with a sleep apnoea diagnosis (International Classification of Diseases (ICD)-9 3472 or ICD-10 G47.3) and 443\u2009463 disease-free controls. We replicated our analysis in the Estonian Biobank.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>We identified a significant association within the serotonin receptor 1F (<jats:italic>HTR1F<\/jats:italic>) locus (rs1818163, \u03b2=0.059, <jats:sc>se<\/jats:sc>=0.010, p=1.58\u00d710<jats:sup>\u2212<\/jats:sup>\n                     <jats:sup>8<\/jats:sup>), and replicated the association in the Estonian Biobank (\u03b2=0.042, <jats:sc>se<\/jats:sc>=0.020, p=0.034). The association signal colocalised with <jats:italic>HTR1F<\/jats:italic> expression across multiple tissues (posterior probability &gt;0.8), and single-cell sequencing implicated <jats:italic>HTR1F<\/jats:italic> expression, particularly in neurons. Analysis of expression quantitative trait locus data further supported a possible regulatory role in neurons (\u03b2=\u2005\u22120.03, p=1.2\u00d710<jats:sup>\u22124<\/jats:sup>). Finally, phenome-wide association study analysis of rs1818163 showed an association with objectively measured sleep-activity data, specifically with the number of awakenings during the night (p=5.6\u00d710<jats:sup>\u22128<\/jats:sup>).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>The findings indicate that <jats:italic>HTR1F<\/jats:italic> is associated with sleep apnoea, particularly in the non-obese patient population, and provide insight into the growing evidence of serotonin signalling as a factor modulating liability to sleep apnoea.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1183\/13993003.01778-2024","type":"journal-article","created":{"date-parts":[[2025,6,26]],"date-time":"2025-06-26T11:45:25Z","timestamp":1750938325000},"page":"2401778","update-policy":"https:\/\/doi.org\/10.1183\/ers-crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Genetic associations between serotonin receptor 1F (<i>HTR1F<\/i>) regulatory variation and sleep apnoea in non-obese individuals: insights from GWAS and eQTL analyses"],"prefix":"10.1183","volume":"66","author":[{"given":"Satu","family":"Strausz","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Broberg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0153-922X","authenticated-orcid":false,"given":"Samuel 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