Genome-wide analysis in over 1.6 million participants uncovers 147 loci associated with obstructive sleep apnoea
Garcia-Marin, L. M.; Ceja, Z.; Parasuraman, A.; Xu, J.; Diaz-Torres, S.; Flores-Ocampo, V.; Aman, A. M.; Maya-Martinez, M.; Huang, X.; Pasquali, C.; Aguilar-Roldan, A.; Uckac, B.; Cao, F.; Ogonowski, N. S.; Martin, N. G.; MacGregor, S.; Dong, X.; Lewis, S. J.; Saviiri, M.; Wang, J.; Renteria, M. E.
Show abstract
We conducted the largest GWAS meta-analysis for obstructive sleep apnoea (OSA; Ncases= 230,657; Ncontrols= 1,377,442) using European ancestry genetic data from five countries. We identified 147 independent loci associated with OSA, and estimated SNP-based heritability at 16%. We report six independent loci in a separate African population meta-analysis (Ncases= 46,834; Ncontrols= 149,192). We observed spatially resolved gene enrichment involving GABAergic and glutamate pathways, synaptic transmission, and cytoskeletal remodelling. OSA-derived polygenic risk scores showed predictive ability for clinician ascertained OSA status, Fitbit-derived sleep features, and self-reported sleep traits in participants of diverse ancestral backgrounds. We identified putative causal relationships with ADHD, depression, multisite chronic pain, body mass index, and schizophrenia, among others. Our findings demonstrate a robust genetic component underlying OSA risk, independent of body mass index, implicating distinct neurobiological pathways related to synaptic function and corticothalamic feedback loops.
Matching journals
The top 3 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Genome-wide association analysis of excessive daytime sleepiness identifies 42 loci that suggest phenotypic subgroups 95%
- Whole Genome Sequencing Analysis Of Body Mass Index Identifies Novel African Ancestry-Specific Risk Allele 94%
- Alternative splicing in the lung influences COVID-19 severity and respiratory diseases 93%
Similar papers in this journal
- Signatures Of TSPAN8 Variants Associated With Human Metabolic Regulation And Diseases 93%
- Sex-dependent placental mQTL provide insight into the prenatal origins of childhood-onset traits and conditions 93%
- Sleep-dependent engram reactivation during hippocampal memory consolidation is associated with subregion-specific biosynthetic changes 93%
Similar papers in this journal
- Electrophysiological measures from human iPSC-derived neurons are associated with schizophrenia clinical status and predict individual cognitive performance 92%
- Global patterns of genetic variation and association with clinical phenotypes at genes involved in SARS-CoV-2 infection 92%
- Developing forebrain synapses are uniquely vulnerable to sleep loss 92%
Similar papers in this journal
- Genome-wide analysis of binge-eating disorder identifies the first three risk loci and implicates iron metabolism 94%
- Genome-wide analysis in 756,646 individuals provides first genetic evidence that ACE2 expression influences COVID-19 risk and yields genetic risk scores predictive of severe disease 93%
- The impact of rare protein coding genetic variation on adult cognitive function 93%
Similar papers in this journal
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.