Forward and reverse genomic screens enhance the understanding of phenotypic variation in a large Chinese rhesus macaque cohort
Combining genotype and phenotype data promises to greatly increase the value of macaque as biomedical models for human disease. Here we launch the Macaque Biobank project by deeply sequencing 919 captive Chinese rhesus macaques (CRM) while assessing 52 phenotypic traits. Genomic analyses reveal the captive CRMs are a mixture of multiple wild sources and exhibit significantly lower mutational load than their Indian counterparts. We identify hundreds of loss-of-function variants linked to human inherited disease and drug targets, and at least seven exert significant effects on phenotypes using forward genomic screens. Genome-wide association analyses reveal 30 independent loci associated with phenotypic variations. Using reverse genomic approaches, we identify DISC1 (p.Arg517Trp) as a genetic risk factor for neuropsychiatric disorders, with macaques carrying this deleterious allele exhibiting impairments in working memory and cortical architecture. This study demonstrates the potential of macaque cohorts for the investigation of genotype-phenotype relationships and exploring potential spontaneous models of human genetic disease.
Authors
- Minmin Yang (ORCID: https://orcid.org/0000-0003-1148-7347)
- Yijiang Li
- Ning Liu (ORCID: https://orcid.org/0000-0001-6662-6709)
- Xinran You (ORCID: https://orcid.org/0009-0008-0355-6764)
- Dong‐Dong Wu (ORCID: https://orcid.org/0000-0001-7101-7297)
- Ping Zheng (ORCID: https://orcid.org/0000-0003-0402-5507)
- D.N. Cooper (ORCID: https://orcid.org/0000-0002-8943-8484)
- Yizeng Lu (ORCID: https://orcid.org/0000-0002-5198-0155)
- Longbao Lv (ORCID: https://orcid.org/0000-0002-8437-6333)
- Hongdi Huang (ORCID: https://orcid.org/0000-0001-7873-1282)
- Nanhui Chen (ORCID: https://orcid.org/0000-0001-5075-5848)
- Yang Wu (ORCID: https://orcid.org/0000-0002-0128-7280)
- Y X Chen
- Yanling Li (ORCID: https://orcid.org/0000-0002-6277-1869)
- Yun Wang (ORCID: https://orcid.org/0000-0002-3644-3466)
- Yali Zhang (ORCID: https://orcid.org/0000-0002-9115-5758)
- Qiong Wang (ORCID: https://orcid.org/0000-0002-0835-3770)
- Jianhong Wang
- Xiaomei Yu
- Baolin Zhang (ORCID: https://orcid.org/0000-0002-4559-1567)
- Yong‐Gang Yao (ORCID: https://orcid.org/0000-0002-2955-0693)
- Hexian Duan
- Wenxian Xiao
- Yi Zhang (ORCID: https://orcid.org/0009-0009-9196-6508)
- Mengying Qiu
- Yicheng Qiao
Institutions
- Kunming Institute of Zoology (CN)
- Chinese Academy of Sciences (CN)
- Sichuan University (CN)
- West China Hospital of Sichuan University (CN)
- Institute of Biophysics (CN)
- University of Chinese Academy of Sciences (CN)
- Cardiff University (GB)
- University of Hong Kong (HK)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-09-30
- DOI
- https://doi.org/10.1038/s41467-025-63747-x
- Primary Topic
- Primate Behavior and Ecology
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Chinese Academy of Sciences
- Institute of Zoology, Chinese Academy of Sciences
- Kunming Institute of Zoology, Chinese Academy of Sciences
- National Key Research and Development Program of China