Influence of Ancestry and Molecular Markers on the Severity of Obstructive Sleep Apnea: A Systematic Review and Meta-Analysis.

Genetic susceptibility to obstructive sleep apnea (OSA) may vary by ancestry. We have conducted a systematic review and random-effects meta-analysis of observational studies (International Prospective Register of Systematic Reviews [PROSPERO] CRD42024548801) to test whether ancestry modifies the associations involving specific genetic polymorphisms and OSA risk and severity. We searched databases until June 2024 for studies examining variants (interleukin-6 (IL6) rs1800795, tumor necrosis factor (TNF) rs1800629, solute carrier family 6 member 4 (serotonin-transporter gene) (SLC6A4) serotonin-transporter-linked polymorphic region (5-HTTLPR)/serotonin transporter intron 2 (VNTR) (STin2), 5-hydroxytryptamine (serotonin) receptor 2A gene (HTR2A) rs9526240, leptin receptor (LEPR) rs3790435) and pooled odds ratios (ORs) with 95% confidence interval (CIs); ancestry-specific effects were explored. Five studies included 3,606 participants. The overall association showed an OR = 1.25 (95%CI: 0.85-1.86; I 2  = 76%). By ancestry, Brazilian participants of European descent demonstrated higher risk (OR = 2.80; 95%CI: 1.11-7.08), while those of West-African ancestry showed protection (OR = 0.26; 95%CI: 0.09-0.74). Genetic associations with OSA differ significantly by ancestry, supporting ancestry-informed study designs and larger multiethnic cohorts for personalized OSA management.