Hang Zhou, PhD

The central goal of my graduate and postdoctoral work is to understand the human genome and how it affects human traits and diseases. To reach this goal, I completed training in computational biology and population genetics during PhD and psychiatric genetics as a postdoc. I performed a series of genetic studies on natural selection in the human genome and genome-wide studies on substance use disorders (SUDs) and comorbid psychiatric diseases.

Over the past years, I led the analytic effort for several projects in the Million Veteran Program (MVP) using large-scale genomic data and electronic health records. We conducted the largest multi-ancestry genome-wide association study (GWAS) on alcohol consumption and AUD (Kranzler*, Zhou*, Kember* et al., Nature Communications, 2019). This study delivered a key message that changed this field: AUD differs from alcohol consumption genetically. Subsequently, we made significant contributions to this field (Zhou et al., Nature Neuroscience, 2020; Zhou et al., Neuropsychopharmacology, 2022; Zhou et al., Nature Medicine, 2023; Zhou et al., Journal of Clinical Investigation, 2024). We also conducted a large genetic study of opioid use disorder (OUD) and identified the functional coding variant Asn40Asp in OPRM1 associated with OUD (Zhou et al., JAMA Psychiatry, 2020). Collectively, these studies represent important advances in the field.

There is limited knowledge in the literature regarding the role of rare coding variants in SUDs. My lab developed analytical pipelines to process more than 4,500 in-house whole-exome sequencing (WES) samples—from raw sequencing reads to variant calling, quality control, annotation, and functional prediction. We then conducted single-variant and gene-based collapsing analyses, integrating these data with the UK Biobank WES data. Our work represents the first comprehensive WES studies of SUDs, leveraging cross-ancestry datasets to identify novel rare variants and genes (Wang et al., Biological Psychiatry, 2025; Wang et al., Translational Psychiatry, 2025).

Currently, my lab is working on whole-genome sequencing (WGS) projects integrating multi-ancestry biobank-level resources, including the MVP, UK Biobank, and All of Us Program. We aim to find novel rare, common, and structural variants associated with AUD and recover the missing heritability, improve causal variant identification and disease prediction using a novel whole-genome polygenic risk score framework, and identify cell subtypes and key cellular processes in the human brain.