Exome sequencing of Alcohol-associated Hepatitis. Exome sequencing of Alcohol-associated Hepatitis

Alcoholic hepatitis (AH) is a clinically severe, acute disease that only afflicts a fraction of patients with alcohol use disorder (AUD). Although recent genomic studies of alcoholic cirrhosis (AC) and steatosis have revealed that several genes of large effect are shared between these disorders, the genetic and environmental sources of variation that lead to AH, AC or alcohol fatty liver disease (AFLD) in some AUD patients remain largely unknown. In order to investigate the genetic determinants of AH, we sequenced a 58 Mb exome target to high genotype accuracy (0.996) and completeness (0.941) in 1,735 patients with AH (N=784) and heavy drinking controls without alcohol-associated liver disease (ALD) (N=951), detecting 1,085,982 unique single nucleotide variants (SNVs). Analysis of... (for more see dbGaP study page.)

酒精性肝炎（Alcoholic hepatitis, AH）是一种临床重症急性疾病，仅会累及部分酒精使用障碍（Alcohol use disorder, AUD）患者。尽管近期针对酒精性肝硬化（Alcoholic cirrhosis, AC）与脂肪变性的基因组研究已揭示，此类疾病共享多个效应显著的基因，但导致部分AUD患者发展为AH、AC或酒精性脂肪肝（Alcohol fatty liver disease, AFLD）的遗传与环境变异来源，目前仍尚未明确。为探究AH的遗传决定因素，本研究对1735名受试者的58 Mb外显子组靶向区域进行测序，使其基因型准确率达0.996、覆盖完整度达0.941；其中受试者包括784名AH患者，以及951名无酒精相关肝病（Alcohol-associated liver disease, ALD）的重度饮酒对照人群。本研究共检测到1085982个独特的单核苷酸变异（Single nucleotide variants, SNVs）。后续分析详见……（更多内容请参见dbGaP研究页面）