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Targeted Genome Sequencing Identifies Multiple Rare Variants in Caveolin-1 Associated with Obstructive Sleep Apnea.
Thursday,2022-07-21 19:12 America/Los_Angeles — ecterry
| Title | Targeted Genome Sequencing Identifies Multiple Rare Variants in Caveolin-1 Associated with Obstructive Sleep Apnea. |
| Publication Type | Journal Article |
| Year of Publication | 2022 |
| Authors | Liang, J, Wang, H, Cade, BE, Kurniansyah, N, He, KY, Lee, J, Sands, SA, Brody, J, Chen, H, Gottlieb, DJ, Evans, DS, Guo, X, Gharib, SA, Hale, L, Hillman, DR, Lutsey, PL, Mukherjee, S, Ochs-Balcom, HM, Palmer, LJ, Purcell, S, Saxena, R, Patel, SR, Stone, KL, Tranah, GJ, Boerwinkle, E, Lin, X, Liu, Y, Psaty, BM, Vasan, RS, Manichaikul, A, Rich, SS, Rotter, JI, Sofer, T, Redline, S, Zhu, X |
| Corporate/Institutional Authors | TOPMed Sleep Working Group |
| Journal | Am J Respir Crit Care Med |
| Date Published | 2022 Jul 13 |
| ISSN | 1535-4970 |
| Abstract | <p><b>INTRODUCTION: </b>Obstructive sleep apnea (OSA) is a common disorder associated with increased risk for cardiovascular disease, diabetes, and premature mortality. There is strong clinical and epi-demiologic evidence supporting the importance of genetic factors influencing OSA, but limited data implicating specific genes.</p><p><b>METHODS: </b>Leveraging high depth genomic sequencing data from the National Heart, Lung, and Blood Institute (NHLBI) Trans-Omics for Precision Medicine (TOPMed) program and imputed genotype data from multiple population-based studies, we performed linkage analysis in the Cleve-land Family Study (CFS) followed by multi-stage gene-based association analyses in independent cohorts to search for rare variants contributing to OSA severity as assessed by the apnea-hypopnea index (AHI) in a total of 7,708 individuals of European ancestry.</p><p><b>RESULTS: </b>Linkage analysis in CFS identified a suggestive linkage peak on chromosome 7q31 (LOD=2.31). Gene-based analysis identified 21 non-coding rare variants in Caveolin-1 (CAV1) associated with lower AHI after accounting for multiple comparisons (p=7.4×10-8). These non-coding variants together significantly contributed to the linkage evidence (p<10-3). Follow-up anal-ysis revealed significant associations between these variants and increased CAV1 expression, and increased CAV1 expression in peripheral monocytes was associated with lower AHI (p=0.024) and higher minimum overnight oxygen saturation (p=0.007).</p><p><b>CONCLUSION: </b>Rare variants in CAV1, a membrane scaffolding protein essential in multiple cellular and metabolic functions, are associated with higher CAV1 gene expression and lower OSA severity, suggesting a novel target for modulating OSA severity.</p> |
| DOI | 10.1164/rccm.202203-0618OC |
| Alternate Journal | Am J Respir Crit Care Med |
| PubMed ID | 35822943 |
ePub date:
22/07