Lipolysis and gestational diabetes mellitus onset: a case-cohort genome-wide association study in Chinese

Miao Zhang; Qing Li; Kai-Lin Wang; Yao Dong; Yu-Tong Mu; Yan-Min Cao; Jin Liu; Zi-Heng Li; Hui-Lu Cui; Hai-Yan Liu; An-Qun Hu; Ying-Jie Zheng

doi:10.1186/s12967-023-03902-4

Lipolysis and gestational diabetes mellitus onset: a case-cohort genome-wide association study in Chinese

J Transl Med. 2023 Jan 25;21(1):47. doi: 10.1186/s12967-023-03902-4.

Authors

Miao Zhang^#^{1

2

3}, Qing Li^#⁴, Kai-Lin Wang^{1

2

3}, Yao Dong^{1

2

3}, Yu-Tong Mu^{1

2

3}, Yan-Min Cao^{1

2

3}, Jin Liu^{1

2

3}, Zi-Heng Li^{1

2

3}, Hui-Lu Cui^{1

2

3}, Hai-Yan Liu⁵, An-Qun Hu⁶, Ying-Jie Zheng^{7

8

9}

Affiliations

¹ Department of Epidemiology, School of Public Health, Fudan University, Shanghai, 200032, China.
² Key Laboratory for Health Technology Assessment, National Commission of Health and Family Planning, Fudan University, Shanghai, 200032, China.
³ Key Laboratory of Public Health Safety, Ministry of Education, Fudan University, Shanghai, 200032, China.
⁴ Department of Obstetrics and Gynecology, Anqing Municipal Hospital, Anqing, 246003, China.
⁵ Department of Clinical Laboratory, Anqing Municipal Hospital, Anqing, 246003, China. lhyan929@163.com.
⁶ Department of Clinical Laboratory, Anqing Municipal Hospital, Anqing, 246003, China. haq0828@hotmail.com.
⁷ Department of Epidemiology, School of Public Health, Fudan University, Shanghai, 200032, China. yjzheng@fudan.edu.cn.
⁸ Key Laboratory for Health Technology Assessment, National Commission of Health and Family Planning, Fudan University, Shanghai, 200032, China. yjzheng@fudan.edu.cn.
⁹ Key Laboratory of Public Health Safety, Ministry of Education, Fudan University, Shanghai, 200032, China. yjzheng@fudan.edu.cn.

^# Contributed equally.

Abstract

Background: Genetic knowledge of gestational diabetes mellitus (GDM) in Chinese women is quite limited. This study aimed to identify the risk factors and mechanism of GDM at the genetic level in a Chinese population.

Methods: We conducted a genome-wide association study (GWAS) based on single nucleotide polymorphism (SNP) array genotyping (ASA-CHIA Bead chip, Illumina) and a case-cohort study design. Variants including SNPs, copy number variants (CNVs), and insertions-deletions (InDels) were called from genotyping data. A total of 2232 pregnant women were enrolled in their first/second trimester between February 2018 and December 2020 from Anqing Municipal Hospital in Anhui Province, China. The GWAS included 193 GDM patients and 819 subjects without a diabetes diagnosis, and risk ratios (RRs) and their 95% confidence intervals (CIs) were estimated by a regression-based method conditional on the population structure. The calling and quality control of genotyping data were performed following published guidelines. CNVs were merged into CNV regions (CNVR) to simplify analyses. To interpret the GWAS results, gene mapping and overexpression analyses (ORAs) were further performed to prioritize the candidate genes and related biological mechanisms.

Results: We identified 14 CNVRs (false discovery rate corrected P values < 0.05) and two suggestively significant SNPs (P value < 0.00001) associated with GDM, and a total of 19 candidate genes were mapped. Ten genes were significantly enriched in gene sets related to lipase (triglyceride lipase and lipoprotein lipase) activity (LIPF, LIPK, LIPN, and LIPJ genes), oxidoreductase activity (TPH1 and TPH2 genes), and cellular components beta-catenin destruction complex (APC and GSK3B genes), Wnt signalosome (APC and GSK3B genes), and lateral element in the Gene Ontology resource (BRCA1 and SYCP2 genes) by two ORA methods (adjusted P values < 0.05).

Conclusions: Genes related to lipolysis, redox reaction, and proliferation of islet β-cells are associated with GDM in Chinese women. Energy metabolism, particularly lipolysis, may play an important role in GDM aetiology and pathology, which needs further molecular studies to verify.

Keywords: Genome-wide association study; Gestational diabetes mellitus; Lipolysis; Metabolism.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cohort Studies
Diabetes, Gestational* / genetics
East Asian People
Female
Genome-Wide Association Study
Humans
Lipolysis
Polymorphism, Single Nucleotide / genetics
Pregnancy