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Advancements in technology over the decades have elevated research from early candidate gene studies to present-day genome-wide scans, unveiling numerous genetic and epigenetic risk factors for AUD. The latest GWAS on more than one million participants identified more than 100 genetic variants, and the largest epigenome-wide association studies (EWAS) in blood and brain samples have revealed tissue-specific epigenetic changes. Downstream analyses revealed enriched pathways, genetic correlations with other traits, transcriptome-wide association in brain tissues, and drug-gene interactions for AUD. We also discuss limitations and future directions, including increasing the power of GWAS and EWAS studies as well as expanding the diversity of populations included in these analyses. Larger samples, novel technologies, and analytic approaches are essential; these include whole-genome sequencing, multiomics, single-cell sequencing, spatial transcriptomics, deep-learning prediction of variant function, and integrated methods for disease risk prediction.<\/jats:p>","DOI":"10.1172\/jci172885","type":"journal-article","created":{"date-parts":[[2024,8,14]],"date-time":"2024-08-14T14:00:45Z","timestamp":1723644045000},"source":"Crossref","is-referenced-by-count":41,"title":["Human genetics and epigenetics of alcohol use disorder"],"prefix":"10.1172","volume":"134","author":[{"given":"Hang","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Psychiatry, Yale School of Medicine, New Haven, Connecticut, USA."},{"name":"Veterans Affairs Connecticut Healthcare System, West Haven, Connecticut, USA."},{"name":"Department of Biomedical Informatics and Data Science,"},{"name":"Center for Brain and Mind 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