Research Paper Volume 13, Issue 7 pp 10619—10658
Identification of novel functional CpG-SNPs associated with Type 2 diabetes and birth weight
- 1 Department of Endocrinology and Metabolism, The Third Affiliated Hospital of Southern Medical University, Guangzhou 510630, China
- 2 Department of Endocrinology and Metabolism, SSL Central Hospital of Dongguan City, Dongguan 523326, China
- 3 Xiangya Nursing School, Central South University, Changsha 410013, China
- 4 Tulane Center for Biomedical Informatics and Genomics, Deming Department of Medicine, School of Medicine, Tulane University, New Orleans, LA 70112, USA
- 5 Department of Endocrinology and metabolism, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou 510330, China
- 6 School of Basic Medical Sciences, Central South University, Changsha 410000, China
Received: November 6, 2020 Accepted: March 4, 2021 Published: April 4, 2021https://doi.org/10.18632/aging.202828
How to Cite
Copyright: © 2021 Liu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Genome-wide association studies (GWASs) have identified hundreds of genetic loci for type 2 diabetes (T2D) and birth weight (BW); however, a large proportion of the total trait heritability remains unexplained. The previous studies were generally focused on individual traits and largely failed to identify the majority of the variants that play key functional roles in the etiology of the disease. Here, we aim to identify novel functional loci for T2D, BW and the pleiotropic variants shared between them by performing a targeted conditional false discovery rate (cFDR) analysis that integrates two independent GWASs with summary statistics for T2D (n = 26,676 cases and 132,532 controls) and BW (n = 153,781) which entails greater statistical power than individual trait analyses. In this analysis, we considered CpG-SNPs, which are SNPs that may influence DNA methylation status, and are therefore considered to be functionally important. We identified 103 novel CpG-SNPs for T2D, 182 novel CpG-SNPs for BW (cFDR < 0.05), and 52 novel pleiotropic loci for both (conjunction cFDR [ccFDR] < 0.05). Among the identified novel CpG-SNPs, 33 were annotated as methylation quantitative trait loci (meQTLs) in whole blood, and 145 displayed at least some effects on meQTL, metabolic QTL (metaQTL), and/or expression QTL (eQTL). These findings may provide further insights into the shared biological mechanisms and functional genetic determinants that overlap between T2D and BW, thereby providing novel potential targets for treatment/intervention development.