Genome-wide association study of maternal plasma metabolites during pregnancy
Metabolites are key indicators of health and therapeutic targets, but their genetic underpinnings during pregnancy-a critical period for human reproduction-are largely unexplored. Using genetic data from non-invasive prenatal testing, we performed a genome-wide association study on 84 metabolites, including 37 amino acids, 24 elements, 13 hormones, and 10 vitamins, involving 34,394 pregnant Chinese women, with sample sizes ranging from 6,394 to 13,392 for specific metabolites. We identified 53 metabolite-gene associations, 23 of which are novel. Significant differences in genetic effects between pregnant and non-pregnant women were observed for 16.7%-100% of these associations, indicating gene-environment interactions. Additionally, 50.94% of genetic associations exhibited pleiotropy among metabolites and between six metabolites and eight pregnancy phenotypes. Mendelian randomization revealed potential causal relationships between seven maternal metabolites and 15 human traits and diseases. These findings provide new insights into the genetic basis of maternal plasma metabolites during pregnancy.
Authors
- Ya Gao (ORCID: https://orcid.org/0000-0002-5094-9842)
- Huanming Yang (ORCID: https://orcid.org/0000-0002-0858-3410)
- Weiqiao Rao (ORCID: https://orcid.org/0000-0001-8624-6703)
- Fengxiang Wei (ORCID: https://orcid.org/0000-0001-7559-2504)
- Fengxia Su (ORCID: https://orcid.org/0000-0003-0724-6284)
- Chao Nie (ORCID: https://orcid.org/0000-0003-3536-0324)
- Nannan Kong
- Xuemei Qiu (ORCID: https://orcid.org/0000-0002-4406-6728)
- Huanhuan Zhu (ORCID: https://orcid.org/0000-0002-2995-4911)
- Jilong Yao
- Liping Huang (ORCID: https://orcid.org/0000-0003-3073-7698)
- Linxuan Li (ORCID: https://orcid.org/0000-0002-7920-4684)
- Yun Zhou (ORCID: https://orcid.org/0000-0002-7075-6351)
- Zengyou Liu
- Shengmou Lin (ORCID: https://orcid.org/0000-0001-9033-3471)
- Xin Jin (ORCID: https://orcid.org/0000-0001-8816-9705)
- Xianmei Lan
- Liang Lin (ORCID: https://orcid.org/0000-0001-7374-7234)
- Qingmei Fu
- Ye Yin (ORCID: https://orcid.org/0000-0002-7051-1987)
- Jianmin Niu (ORCID: https://orcid.org/0000-0002-1182-5994)
- Guixue Hou
- Yuqing Deng
- Yuanqing Chen
- Xuelian He (ORCID: https://orcid.org/0000-0002-6275-1219)
- Rong Wang (ORCID: https://orcid.org/0000-0002-0669-9321)
- Yuan Wang (ORCID: https://orcid.org/0000-0002-0939-1269)
- Jing Zhang (ORCID: https://orcid.org/0000-0002-8449-6554)
- Yan Li (ORCID: https://orcid.org/0000-0002-2867-933X)
- Siqi Liu (ORCID: https://orcid.org/0000-0001-9744-3681)
- Fang Chen (ORCID: https://orcid.org/0000-0003-4971-8729)
- Xun Xu (ORCID: https://orcid.org/0000-0002-5338-5173)
- Siyang Liu
- Dan Jiang (ORCID: https://orcid.org/0000-0002-9187-7152)
- Zilong Li (ORCID: https://orcid.org/0000-0001-5859-2078)
- Xiaoxia Wu (ORCID: https://orcid.org/0000-0001-9375-5266)
- Linlin Wu (ORCID: https://orcid.org/0000-0001-8811-6574)
- Xinhong Liu (ORCID: https://orcid.org/0000-0002-6150-0493)
- Mei Zhao (ORCID: https://orcid.org/0000-0003-0900-8423)
- Jiansheng Xie
- Weihua Zhao
- Likuan Xiong (ORCID: https://orcid.org/0000-0002-8823-5722)
- Liqiong Luo
- Lijian Zhao (ORCID: https://orcid.org/0009-0002-5472-0639)
- Jinghui Ren
- Jian Wang (ORCID: https://orcid.org/0009-0004-4420-1928)
Institutions
- BGI Group (China) (CN)
- Jinan University (CN)
- Longgang Central Hospital (CN)
- Shenzhen Maternity and Child Healthcare Hospital (CN)
- ShenZhen People’s Hospital (CN)
- Peking University Shenzhen Hospital (CN)
- Shenzhen Bao'an District People's Hospital (CN)
- University of Hong Kong - Shenzhen Hospital (CN)
- Wuhan Children's Hospital (CN)
- Shenzhen Luohu People's Hospital (CN)
- Shenzhen Second People's Hospital (CN)
- University of Chinese Academy of Sciences (CN)
- Anshan Hospital (CN)
- BGI Genomics
- BGI Research (CN)
- Huazhong University of Science and Technology (CN)
- University of Hong Kong (HK)
Publication Details
- Journal
- Cell Genomics
- Published
- 2024-10-01
- DOI
- https://doi.org/10.1016/j.xgen.2024.100657
- Citations
- 9
- Primary Topic
- Genetic Associations and Epidemiology
- Type
- article
- Field-Weighted Citation Impact
- 4.95
Funders
- Guangzhou Medical University
- National Natural Science Foundation of China
- University of California, San Francisco
- Basic and Applied Basic Research Foundation of Guangdong Province