|
|
| PMID |
|
|
| TITLE |
|
| Discovery of genomic loci associated with sleep apnoea risk through multi-trait GWAS analysis with snoring. |
|
| ABSTRACT |
|
| STUDY OBJECTIVES |
NlmCategory: OBJECTIVE |
| Despite its association with severe health conditions, the aetiology of sleep apnoea remains understudied. This study sought to identify genetic variants robustly associated with sleep apnoea risk. |
| METHODS |
NlmCategory: METHODS |
| Despite its association with severe health conditions, the aetiology of sleep apnoea remains understudied. This study sought to identify genetic variants robustly associated with sleep apnoea risk. We performed a genome-wide association study (GWAS) meta-analysis of sleep apnoea across five cohorts (NTotal=523,366), followed by a multi-trait analysis of GWAS (MTAG) to boost power, leveraging the high genetic correlation between sleep apnoea and snoring. We then adjusted our results for the genetic effects of body mass index (BMI) using multi-trait-based conditional & joint analysis (mtCOJO) and sought replication of lead hits in a large cohort of participants from 23andMe, Inc (NTotal=1,477,352; Ncases=175,522). We also explored genetic correlations with other complex traits and performed a phenome-wide screen for causally associated phenotypes using the latent causal variable method. |
| RESULTS |
NlmCategory: RESULTS |
| Despite its association with severe health conditions, the aetiology of sleep apnoea remains understudied. This study sought to identify genetic variants robustly associated with sleep apnoea risk. We performed a genome-wide association study (GWAS) meta-analysis of sleep apnoea across five cohorts (NTotal=523,366), followed by a multi-trait analysis of GWAS (MTAG) to boost power, leveraging the high genetic correlation between sleep apnoea and snoring. We then adjusted our results for the genetic effects of body mass index (BMI) using multi-trait-based conditional & joint analysis (mtCOJO) and sought replication of lead hits in a large cohort of participants from 23andMe, Inc (NTotal=1,477,352; Ncases=175,522). We also explored genetic correlations with other complex traits and performed a phenome-wide screen for causally associated phenotypes using the latent causal variable method. Our sleep apnoea meta-analysis identified five independent variants with evidence of association beyond genome-wide significance. After adjustment for BMI, only one genome-wide significant variant was identified. MTAG analyses uncovered 49 significant independent loci associated with sleep apnoea risk. Twenty-nine variants were replicated in the 23andMe GWAS adjusting for BMI. We observed genetic correlations with several complex traits, including multisite chronic pain, diabetes, eye disorders, high blood pressure, osteoarthritis, chronic obstructive pulmonary disease, and BMI-associated conditions. |
| CONCLUSION |
NlmCategory: CONCLUSIONS |
| Despite its association with severe health conditions, the aetiology of sleep apnoea remains understudied. This study sought to identify genetic variants robustly associated with sleep apnoea risk. We performed a genome-wide association study (GWAS) meta-analysis of sleep apnoea across five cohorts (NTotal=523,366), followed by a multi-trait analysis of GWAS (MTAG) to boost power, leveraging the high genetic correlation between sleep apnoea and snoring. We then adjusted our results for the genetic effects of body mass index (BMI) using multi-trait-based conditional & joint analysis (mtCOJO) and sought replication of lead hits in a large cohort of participants from 23andMe, Inc (NTotal=1,477,352; Ncases=175,522). We also explored genetic correlations with other complex traits and performed a phenome-wide screen for causally associated phenotypes using the latent causal variable method. Our sleep apnoea meta-analysis identified five independent variants with evidence of association beyond genome-wide significance. After adjustment for BMI, only one genome-wide significant variant was identified. MTAG analyses uncovered 49 significant independent loci associated with sleep apnoea risk. Twenty-nine variants were replicated in the 23andMe GWAS adjusting for BMI. We observed genetic correlations with several complex traits, including multisite chronic pain, diabetes, eye disorders, high blood pressure, osteoarthritis, chronic obstructive pulmonary disease, and BMI-associated conditions. Our study uncovered multiple genetic loci associated with sleep apnoea risk, thus increasing our understanding of the aetiology of this condition and its relationship with other complex traits. |
| © Sleep Research Society 2022. Published by Oxford University Press on behalf of the Sleep Research Society. |
|
| DATE PUBLISHED |
|
|
| HISTORY |
|
| PUBSTATUS |
PUBSTATUSDATE |
| received |
2022/02/18 |
| entrez |
2022/12/16 15:53 |
| pubmed |
2022/12/17 06:00 |
| medline |
2022/12/17 06:00 |
|
| AUTHORS |
|
| NAME |
COLLECTIVENAME |
LASTNAME |
FORENAME |
INITIALS |
AFFILIATION |
AFFILIATIONINFO |
| Campos AI |
|
Campos |
Adrian I |
AI |
|
Institute for Molecular Bioscience, The University of Queensland, Brisbane QLD, Australia. |
| Ingold N |
|
Ingold |
Nathan |
N |
|
School of Biomedical Sciences, Faculty of Health, Queensland University of Technology, Brisbane, Queensland, Australia. |
| Huang Y |
|
Huang |
Yunru |
Y |
|
23andMe, Inc., Sunnyvale, CA, USA. |
| Mitchell BL |
|
Mitchell |
Brittany L |
BL |
|
School of Biomedical Sciences, Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia. |
| Kho PF |
|
Kho |
Pik-Fang |
PF |
|
Division of Cardiovascular Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA. |
| Han X |
|
Han |
Xikun |
X |
|
Program in Genetic Epidemiology and Statistical Genetics, Harvard University T.H. Chan School of Public Health, Boston, MA, USA. |
| García-Marín LM |
|
García-Marín |
Luis M |
LM |
|
School of Biomedical Sciences, Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia. |
| Ong JS |
|
Ong |
Jue-Sheng |
JS |
|
QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia. |
|
23andMe Research Team |
|
|
|
|
|
| Law MH |
|
Law |
Matthew H |
MH |
|
School of Biomedical Sciences, Faculty of Health, Queensland University of Technology, Brisbane, Queensland, Australia. |
| Yokoyama JS |
|
Yokoyama |
Jennifer S |
JS |
|
Weill Institute of Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco. |
| Martin NG |
|
Martin |
Nicholas G |
NG |
|
QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia. |
| Dong X |
|
Dong |
Xianjun |
X |
|
Department of Neurology, Brigham & Women's Hospital and Harvard Medical School, Boston, MA, USA. |
| Cuellar-Partida G |
|
Cuellar-Partida |
Gabriel |
G |
|
23andMe, Inc., Sunnyvale, CA, USA. |
| MacGregor S |
|
MacGregor |
Stuart |
S |
|
QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia. |
| Aslibekyan S |
|
Aslibekyan |
Stella |
S |
|
23andMe, Inc., Sunnyvale, CA, USA. |
| Rentería ME |
|
Rentería |
Miguel E |
ME |
|
School of Biomedical Sciences, Faculty of Health, Queensland University of Technology, Brisbane, Queensland, Australia. |
|
| INVESTIGATORS |
|
|
| JOURNAL |
|
| VOLUME: |
| ISSUE: |
| TITLE: Sleep |
| ISOABBREVIATION: Sleep |
| YEAR: 2022 |
| MONTH: Dec |
| DAY: 16 |
| MEDLINEDATE: |
| SEASON: |
| CITEDMEDIUM: Internet |
| ISSN: 1550-9109 |
| ISSNTYPE: Electronic |
|
| MEDLINE JOURNAL |
|
| MEDLINETA: Sleep |
| COUNTRY: United States |
| ISSNLINKING: 0161-8105 |
| NLMUNIQUEID: 7809084 |
|
| PUBLICATION TYPE |
|
| PUBLICATIONTYPE TEXT |
| Journal Article |
|
| COMMENTS AND CORRECTIONS |
|
|
| GRANTS |
|
|
| GENERAL NOTE |
|
|
| KEYWORDS |
|
| KEYWORD |
| GWAS |
| Sleep apnoea |
| genetics |
| snoring |
|
| MESH HEADINGS |
|
|
| SUPPLEMENTARY MESH |
|
|
| GENE SYMBOLS |
|
|
| CHEMICALS |
|
|
| OTHER ID's |
|
|
|
