Hang Zhou, PhD, assistant professor of psychiatry and of biomedical informatics and data science, has been awarded two federal grants to continue his study of the genetics of alcohol use disorder (AUD).
Zhou was awarded an NIH R01 grant to further his investigation of the missing components of AUD’s genetic etiology. He will leverage large-scale whole-genome sequencing datasets from multiple biobanks.
The project aims to identify novel rare, common, and structural variants associated with AUD, enhance causal variant identification and disease risk prediction, and uncover key biology in the human brain. Yale researchers Joel Gelernter, MD, and Hongyu Zhao, PhD, will collaborate on the project.
Zhou was also awarded an NIH R21 grant to support an exploratory project aimed at uncovering the missing heritability of substance use disorders and developing a novel whole-genome polygenic risk score framework to advance understanding of their genetic mechanisms.
AUD is a complex trait, and many risk variants contribute to its etiology. Large-scale human genetic and genomic data are essential to decoding the genetic mechanism underlying the etiology of AUD.
Zhou, Gelernter and their team have led several innovative projects and delivered key findings, including:
- The genetic architecture of alcohol consumption differs from that of AUD;
- Substantial shared genetic architecture of AUD across ancestries, with cross-ancestry fine-mapping improved the identification of potential causal variants;
- Multiple genes have been prioritized with convergent evidence linking their associations with AUD to brain biology;
- Conducted the first whole-exome sequencing study of AUD and identified novel rare variants and genes.
While these findings have significantly advanced our knowledge of the genetics of AUD, there are knowledge gaps concerning rare and structural variants in the entire genome and their biological relevance to AUD. Zhou and team look forward to filling the gaps with support from these grants.