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Genetic analysis of obstructive sleep apnoea discovers a strong association with cardiometabolic health

Strausz, Satu ; Ruotsalainen, Sanni ; Ollila, Hanna M. ; Karjalainen, Juha ; Kiiskinen, Tuomo ; Reeve, Mary ; Kurki, Mitja ; Mars, Nina ; Havulinna, Aki S. and Luonsi, Elina , et al. (2021) In European Respiratory Journal 57(5). p.1-17
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/calmodulindependent protein kinase ID)... (More)

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/calmodulindependent 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 (rg=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 (rg>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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
European Respiratory Journal
volume
57
issue
5
article number
2003091
pages
1 - 17
publisher
European Respiratory Society
external identifiers
  • scopus:85099406680
  • pmid:33243845
ISSN
0903-1936
DOI
10.1183/13993003.03091-2020
language
English
LU publication?
yes
additional info
Funding Information: These results allow us to draw several conclusions. First, genetic variation plays an important role in the development of OSA. This is supported by both the SNP heritability estimates and the associated loci. Publisher Copyright: Copyright © 2021 ERS.
id
0628fcdf-d175-4fee-b124-9ff6399ebb20
date added to LUP
2021-12-21 12:49:01
date last changed
2024-06-30 00:02:16
@article{0628fcdf-d175-4fee-b124-9ff6399ebb20,
  abstract     = {{<p>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&lt;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/calmodulindependent 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 (rg=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 (rg&gt;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. </p>}},
  author       = {{Strausz, Satu and Ruotsalainen, Sanni and Ollila, Hanna M. and Karjalainen, Juha and Kiiskinen, Tuomo and Reeve, Mary and Kurki, Mitja and Mars, Nina and Havulinna, Aki S. and Luonsi, Elina and Aly, Dina Mansour and Ahlqvist, Emma and Teder-Laving, Maris and Palta, Priit and Groop, Leif and Reedik Mägi, Mägi and Antti Mäkitie, Mäkitie and Salomaa, Veikko and Bachour, Adel and Tuomi, Tiinamaija and Palotie, Aarno and Palotie, Tuula and Ripatti, Samuli}},
  issn         = {{0903-1936}},
  language     = {{eng}},
  number       = {{5}},
  pages        = {{1--17}},
  publisher    = {{European Respiratory Society}},
  series       = {{European Respiratory Journal}},
  title        = {{Genetic analysis of obstructive sleep apnoea discovers a strong association with cardiometabolic health}},
  url          = {{http://dx.doi.org/10.1183/13993003.03091-2020}},
  doi          = {{10.1183/13993003.03091-2020}},
  volume       = {{57}},
  year         = {{2021}},
}