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Sequencing Analysis at 8p23 Identifies Multiple Rare Variants in DLC1 Associated with Sleep-Related Oxyhemoglobin Saturation Level.
Wednesday,2019-12-04 15:54 America/Los_Angeles — ecterry
| Title | Sequencing Analysis at 8p23 Identifies Multiple Rare Variants in DLC1 Associated with Sleep-Related Oxyhemoglobin Saturation Level. |
| Publication Type | Journal Article |
| Year of Publication | 2019 |
| Authors | Liang, J, Cade, BE, He, KY, Wang, H, Lee, J, Sofer, T, Williams, S, Li, R, Chen, H, Gottlieb, DJ, Evans, DS, Guo, X, Gharib, SA, Hale, L, Hillman, DR, Lutsey, PL, Mukherjee, S, Ochs-Balcom, HM, Palmer, LJ, Rhodes, J, Purcell, S, Patel, SR, Saxena, R, Stone, KL, Tang, W, Tranah, GJ, Boerwinkle, E, Lin, X, Liu, Y, Psaty, BM, Vasan, RS, Cho, MH, Manichaikul, A, Silverman, EK, R Barr, G, Rich, SS, Rotter, JI, Wilson, JG, Redline, S, Zhu, X |
| Corporate/Institutional Authors | NHLBI Trans-Omics for Precision Medicine (TOPMed), TOPMed Sleep Working Group |
| Journal | Am J Hum Genet |
| Volume | 105 |
| Issue | 5 |
| Pagination | 1057-1068 |
| Date Published | 2019 Nov 07 |
| ISSN | 1537-6605 |
| Abstract | <p>Average arterial oxyhemoglobin saturation during sleep (AvSpOS) is a clinically relevant measure of physiological stress associated with sleep-disordered breathing, and this measure predicts incident cardiovascular disease and mortality. Using high-depth whole-genome sequencing data from the National Heart, Lung, and Blood Institute (NHLBI) Trans-Omics for Precision Medicine (TOPMed) project and focusing on genes with linkage evidence on chromosome 8p23, we observed that six coding and 51 noncoding variants in a gene that encodes the GTPase-activating protein (DLC1) are significantly associated with AvSpOS and replicated in independent subjects. The combined DLC1 association evidence of discovery and replication cohorts reaches genome-wide significance in European Americans (p = 7.9 × 10). A risk score for these variants, built on an independent dataset, explains 0.97% of the AvSpOS variation and contributes to the linkage evidence. The 51 noncoding variants are enriched in regulatory features in a human lung fibroblast cell line and contribute to DLC1 expression variation. Mendelian randomization analysis using these variants indicates a significant causal effect of DLC1 expression in fibroblasts on AvSpOS. Multiple sources of information, including genetic variants, gene expression, and methylation, consistently suggest that DLC1 is a gene associated with AvSpOS.</p> |
| DOI | 10.1016/j.ajhg.2019.10.002 |
| Alternate Journal | Am. J. Hum. Genet. |
| PubMed ID | 31668705 |
| PubMed Central ID | PMC6849112 |
ePub date:
19/11