Lower Oxygen Saturation During Sleep Is Associated with Reduced Expressions of CD1D and RAB20 That Is Potentially Reversed by CPAP Therapy

Li, R.; Joehanes, Roby; Lin, Honghuang; Gower, Adam C.; Cade, Brian E.; Li, J.; Williams, Stephanie; Wang, H.; Punjabi, N.M.; Mehra, Reena; Patel, Sanjay R.; Quan, Stuart F.; Liu, Y.; Gharib, Sina A.; Rotter, Jerome I.; Rich, Stephen S.; Levy, Daniel; Spira, Avrum; Redline, Susan; Gottlieb, Daniel J.; Sofer, Tamar

doi:10.1164/ajrccm-conference.2019.199.1_meetingabstracts.a5604

C99. Srn: Cardiometabolic Consequences of Sleep Disordered Breathing and the Role of Cpap Therapy 2019

DOI: 10.1164/ajrccm-conference.2019.199.1_meetingabstracts.a5604

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Lower Oxygen Saturation During Sleep Is Associated with Reduced Expressions of CD1D and RAB20 That Is Potentially Reversed by CPAP Therapy

R. Li

Roby Joehanes

Honghuang Lin

et al.

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2022

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“…(THADA Armadillo Repeat Containing) gene and was previously associated with glycemic traits(52). It was also associated with p-value=0.004 with minimum oxyhemoglobin saturation during sleep(53). Another replicated SNP at nominal significance (replication p-value=0.04), rs540606, is near the CAMKMT (Calmodulin-Lysine N-Methyltransferase) gene, thought to be involved in calcium signaling…”

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Genome-wide association study of obstructive sleep apnea in the Million Veteran Program uncovers genetic heterogeneity by sex

Sofer

Kurniansyah

Murray

et al. 2022

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Background: Genome-wide association studies (GWAS) for obstructive sleep apnea (OSA) are limited due to the underdiagnosis of OSA, leading to misclassification of OSA, which consequently reduces statistical power. We performed a GWAS of OSA in the Million Veteran Program (MVP) of the U.S. Department of Veterans Affairs (VA) healthcare system, where OSA prevalence is close to its true population prevalence. Methods: We performed GWAS of 568,576 MVP participants, stratified by biological sex and by harmonized race/ethnicity and genetic ancestry (HARE) groups of White, Black, Hispanic, and Asian individuals. We considered both BMI adjusted (BMI-adj) and unadjusted (BMI-unadj) models. We replicated associations in independent datasets, and analyzed the heterogeneity of OSA genetic associations across HARE and sex groups. We finally performed a larger meta-analysis GWAS of MVP, FinnGen, and the MGB Biobank, totaling 916,696 individuals. Findings: MVP participants are 91% male. OSA prevalence is 21%. In MVP there were 18 and 6 genome-wide significant loci in BMI-unadj and BMI-adj analyses, respectively, corresponding to 21 association regions. Of these, 17 were not previously reported in association with OSA, and 13 replicated in FinnGen (False Discovery Rate p-value<0.05). There were widespread significant differences in genetic effects between men and women, but less so across HARE groups. Meta-analysis of MVP, FinnGen, and MGB biobank revealed 17 additional, novel, genome-wide significant regions. Interpretation: Sex differences in genetic associations with OSA are widespread, likely associated with multiple OSA risk factors. OSA shares genetic underpinnings with several sleep phenotypes, suggesting shared etiology and causal pathways.

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confidence: 96%

Genome-wide association study of obstructive sleep apnea in the Million Veteran Program uncovers genetic heterogeneity by sex

Sofer

Kurniansyah

Murray

et al. 2022

Preprint

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Lower Oxygen Saturation During Sleep Is Associated with Reduced Expressions of CD1D and RAB20 That Is Potentially Reversed by CPAP Therapy

Cited by 1 publication

References 0 publications

Genome-wide association study of obstructive sleep apnea in the Million Veteran Program uncovers genetic heterogeneity by sex

Genome-wide association study of obstructive sleep apnea in the Million Veteran Program uncovers genetic heterogeneity by sex

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