Genetic analysis of obstructive sleep apnoea discovers a strong association with cardiometabolic health
Open accessPublished version of a preprint
Abstract
There is currently limited understanding of the genetic aetiology of obstructive sleep apnoea (OSA). We aimed to identify genetic loci associated with OSA risk, and to test if OSA and its comorbidities share a common genetic background. We conducted the first large-scale genome-wide association study of OSA using the FinnGen study (217 955 individuals) with 16 761 OSA patients identified using nationwide health registries. We estimated 0.08 (95% CI 0.06–0.11) heritability and identified five loci associated with OSA (p<5.0×10 −8 ): rs4837016 near GAPVD1 (GTPase activating protein and VPS9 domains 1), rs10928560 near CXCR4 (C-X-C motif chemokine receptor type 4), rs185932673 near CAMK1D (calcium/calmodulin-dependent protein kinase ID) and rs9937053 near FTO (fat mass and obesity-associated protein; a variant previously associated with body mass index (BMI)). In a BMI-adjusted analysis, an association was observed for rs10507084 near RMST / NEDD1 (rhabdomyosarcoma 2 associated transcript/NEDD1 γ-tubulin ring complex targeting factor). We found high genetic correlations between OSA and BMI (r g =0.72 (95% CI 0.62–0.83)), and with comorbidities including hypertension, type 2 diabetes, coronary heart disease, stroke, depression, hypothyroidism, asthma and inflammatory rheumatic disease (r g >0.30). The polygenic risk score for BMI showed 1.98-fold increased OSA risk between the highest and the lowest quintile, and Mendelian randomisation supported a causal relationship between BMI and OSA. Our findings support the causal link between obesity and OSA, and the joint genetic basis between OSA and comorbidities.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Recently, large biobanks have begun analyzing genetic associations with snoring and ICD-based OSA diagnosis.
“Recently, large biobanks have begun analyzing genetic associations with snoring and ICD-based OSA diagnosis.274”
From International Consensus Statement on Obstructive Sleep Apnea (2023) · cites this paper as [274]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
The citation lists haven’t been fetched yet
References 46 · Cited by 194
Research works printed but not linked: 13
- [1]1. Chicago, IL, USA; Athena Matakidou, AstraZeneca, Cambridge, UK;
- [2]2. Heiko Runz, Biogen, Cambridge, MA, USA;
- [3]3. Jimmy Liu, Biogen, Cambridge, MA, USA;
- [35]35. Eaton, Biogen, Cambridge, MA, USA;
- [36]36. Heiko Runz, Biogen, Cambridge, MA, USA;
- [37]37. Sanni Lahdenperä, Biogen, Cambridge, MA, USA;
- [73]73. David Close, AstraZeneca, Cambridge, UK;
- [85]85. David Close, AstraZeneca, Cambridge, UK;
- [86]86. Susan Eaton, Biogen, Cambridge, MA, USA;
- [97]97. Ben Challis, AstraZeneca, Cambridge, UK;
- [115]115. Anne Lehtonen, AbbVie, Chicago, IL, USA; Athena Matakidou, AstraZeneca, Cambridge, UK;
- [130]130. Heiko Runz, Biogen, Cambridge, MA, USA;
- [131]131. Stephanie Loomis, Biogen, Cambridge, MA, USA;
- Authors
- Strausz, S., Ruotsalainen, S., Ollila, H. M., Karjalainen, J., Kiiskinen, T., Reeve, M., Kurki, M., Mars, N., Havulinna, A. S., Luonsi, E., Mansour Aly, D., Ahlqvist, E., Teder-Laving, M., Palta, P., Groop, L., Mägi, R., Mäkitie, A., Salomaa, V., Bachour, A., Tuomi, T., FinnGen, Palotie, A., Palotie, T., & Ripatti, S.
- Affiliations
- University of Helsinki (FI)
- Broad Institute (US)
- Lund University (SE)
- University of Tartu (EE)
- Finnish Institute for Health and Welfare (FI)
- Helsinki University Hospital (FI)
- ORCID
- Venue
- European Respiratory Journal
- Publisher
- European Respiratory Society (ERS)
- Published
- 2020-11-26
- Volume
- 57
- Issue
- 5
- Pages
- 2003091
- ISSN
- 0903-1936 (ISSN-L)
- 1399-3003
- OpenAlex
- W3109235605
- Cited by
- 194
- References
- 46
- Citations by year
- 2026: 22 · 2025: 35 · 2024: 51 · 2023: 37 · 2022: 38 · 2021: 11
- FWCI
- 12.88
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- European Respiratory Journal (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Työväentutkimus Vuosikirja (submittedVersion, other-oa)
- Lund University Publications (Lund University) (submittedVersion)
- Funders
- Academy of Finland Center of Excellence in Complex Disease Genetics (312062, 312074)
- Helsingin Yliopisto (HiLIFE Fellow grants 2017-2020)
- Academy of Finland (285380, 128650, 309643)
- Yrjö Jahnssonin Säätiö
- Biogen
- AstraZeneca
- Business Finland (HUS 4685/31/2016, UH 4386/31/2016)
- Celgene
- GlaxoSmithKline
- Sydäntutkimussäätiö
- Celgene International II Sàrl
- Maze Therapeutics Inc
- Suomen Hammaslääkäriseura Apollonia
- Genentech
- Sanofi
- Horizon 2020 Framework Programme (667301)
- Merck Sharp and Dohme
- Janssen Biotech
- Oskar Öfflund foundation
- Sigrid Juséliuksen Säätiö
- AbbVie
- Pfizer
- Topics
- Health Sciences › Medicine › Physiology › Obstructive Sleep Apnea Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Mapping and Diversity in Plants and Animals
- Keywords
- obstructive sleep apnea, genetic loci, cardiometabolic health, body mass index, obesity, genetic correlation, comorbidities, hypertension, type 2 diabetes, coronary artery disease, stroke, depression, hypothyroidism, asthma, inflammatory rheumatic diseases, polygenic risk score, Mendelian randomization, heritability, CXCR4, CAMK1D, FTO, NEDD1
- MeSH terms
- Alpha-Ketoglutarate-Dependent Dioxygenase FTO, Diabetes Mellitus, Type 2, Humans, Hypertension, Risk Factors, Body Mass Index, Sleep Apnea, Obstructive, Genome-Wide Association Study
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
