Genome-wide association study reveals two novel risk alleles for incident obstructive sleep apnea in the EPISONO cohort

Autor(es)

Tempaku, Priscila Farias ^[1] ; Santoro, Marcos Leite ^{[2, 3]} ; Bittencourt, Lia ^[1] ; D'Almeida, Vania ^[1] ; Belangero, Sintia Iole ^{[2, 3]} ; Tufik, Sergio ^[1]

Afiliação do(s) autor(es)

^[1] Univ Fed Sao Paulo, Dept Psicobiol, Sao Paulo - Brazil

^[2] Univ Fed Sao Paulo, Dept Morfol & Genet, Sao Paulo - Brazil

^[3] Univ Fed Sao Paulo, Dept Psiquiatria, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Sleep Medicine; v. 66, p. 24-32, FEB 2020.
• Citações Web of Science: 0

Resumo

Objective/background: Obstructive sleep apnea (OSA) is a sleep-related breathing disorder that has a complex phenotype. Currently, few genes have been linked with OSA. Thus, the aim of this study was to conduct a genome-wide association study (GWAS) of the apnea-hypopnea index (AHI) variation along time (delta-AHI) in a prospective cohort. Methods: We used data derived from the Sao Paulo Epidemiologic Sleep Study (EPISONO) (n = 1074) cohort, which was followed over eight years (n = 712). Our phenotype of interest was delta-AHI and incident OSA. Further, we were interested on the time-dependent effect of genetic variants. Our final GWAS model used delta-AHI as a dependent variable and the SNPs and covariates as independent variables. We also performed a gene-set and pathway analysis. Results: The delta-AHI increased on average 6.1 events/hour (standard deviation = 14.9) over the followup. We found two significant and 21 suggestive variants associated with delta-AHI. The strongest association (rs12415421) was observed at ST8SIA6 gene and the other significant hit (rs4731117) was in an intergenic region in linkage disequilibrium with our third hit (rs12669165) in the ASB15 gene. We found an effect of the allele rs12415421 for the OSA incidence. Additionally, we observed that individuals with both risk alleles presented a higher incidence of OSA when compared to those with one or without any risk alleles. Conclusions: This study has identified genes in these associated regions with delta-AHI, which seem to be involved in growth and stability of muscle and bone. We also observed an effect of both allele frequencies in the incidence of OSA. (C) 2019 Elsevier B.V. All rights reserved. (AU)

• Processo FAPESP: 18/00955-4 - Estudo do efeito da apneia obstrutiva do sono sobre o comprimento telomérico e seus mecanismos associados
• Beneficiário: Priscila Farias Tempaku
• Modalidade de apoio: Bolsas no Brasil - Doutorado