
Research Square (Research Square), Journal Year: 2023, Volume and Issue: unknown
Published: May 31, 2023
Abstract American Indians (AI) demonstrate the highest rates of both suicidal behaviors (SB) and alcohol use disorders (AUD) among all ethnic groups in US. Rates suicide AUD vary substantially between tribal across different geographical regions, underscoring a need to delineate more specific risk resilience factors. Using data from over 740 AI living within eight contiguous reservations, we assessed genetic factors for SB by investigating: (1) possible overlap with AUD, (2) impacts rare low frequency genomic variants. Suicidal included lifetime history thoughts acts, including verified deaths, scored using ranking variable phenotype (range 0–4). We identified five loci significantly associated two which are intergenic three intronic on genes AACSP1 , ANK1 FBXO11 . Nonsynonymous mutations four SERPINF1 (PEDF), ZNF30 CD34 SLC5A9 non-intronic OPRD1 HSD17B3 one lincRNA were SB. One pathway related hypoxia-inducible factor (HIF) regulation, whose 83 nonsynonymous variants 10 linked as well. Four additional genes, pathways vasopressin-regulated water metabolism cellular hexose transport, also strongly This study represents first investigation an Indian population that has high suicide. Our suggests bivariate association analysis comorbid can increase statistical power; variant high-risk enabled whole-genome sequencing potential identify novel Although such findings may be specific, functional relating PEDF HIF regulation align past reports suggest biological mechanism therapeutic target intervention.
Language: Английский