Uncovering novel regulatory variants in carbohydrate metabolism: a comprehensive multi-omics study of glycemic traits in the Indian population.

Autor: Nair JM; Systems Genomics Laboratory, School of Biotechnology, Jawaharlal Nehru University, New Delhi, 110067, India., Bandesh K; CSIR-Institute of Genomics and Integrative Biology, New Delhi, 110025, India. khushdeepbandesh@gmail.com.; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, India. khushdeepbandesh@gmail.com., Giri AK; CSIR-Institute of Genomics and Integrative Biology, New Delhi, 110025, India.; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, India., Prasad G; CSIR-Institute of Genomics and Integrative Biology, New Delhi, 110025, India.; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, India., Rajashekhar D; CSIR-Institute of Genomics and Integrative Biology, New Delhi, 110025, India., Jha P; CSIR-Institute of Genomics and Integrative Biology, New Delhi, 110025, India.; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, India., Basu A; National Institute of Biomedical Genomics, Kalyani, West Bengal, 741251, India., Tandon N; Department of Endocrinology and Metabolism, All India Institute of Medical Sciences, New Delhi, 110029, India., Bharadwaj D; Systems Genomics Laboratory, School of Biotechnology, Jawaharlal Nehru University, New Delhi, 110067, India. db@jnu.ac.in.
Jazyk: angličtina
Zdroj: Molecular genetics and genomics : MGG [Mol Genet Genomics] 2024 Sep 04; Vol. 299 (1), pp. 85. Date of Electronic Publication: 2024 Sep 04.
DOI: 10.1007/s00438-024-02176-9
Abstrakt: Clinical biomarkers such as fasting glucose, HbA1c, and fasting insulin, which gauge glycemic status in the body, are highly influenced by diet. Indians are genetically predisposed to type 2 diabetes and their carbohydrate-centric diet further elevates the disease risk. Despite the combined influence of genetic and environmental risk factors, Indians have been inadequately explored in the studies of glycemic traits. Addressing this gap, we investigate the genetic architecture of glycemic traits at genome-wide level in 4927 Indians (without diabetes). Our analysis revealed numerous variants of sub-genome-wide significance, and their credibility was thoroughly assessed by integrating data from various levels. This identified key effector genes, ZNF470, DPP6, GXYLT2, PITPNM3, BEND7, and LORICRIN-PGLYRP3. While these genes were weakly linked with carbohydrate intake or glycemia earlier in other populations, our findings demonstrated a much stronger association in the Indian population. Associated genetic variants within these genes served as expression quantitative trait loci (eQTLs) in various gut tissues essential for digestion. Additionally, majority of these gut eQTLs functioned as methylation quantitative trait loci (meth-QTLs) observed in peripheral blood samples from 223 Indians, elucidating the underlying mechanism of their regulation of target gene expression. Specific co-localized eQTLs-meth-QTLs altered the binding affinity of transcription factors targeting crucial genes involved in glucose metabolism. Our study identifies previously unreported genetic variants that strongly influence the diet-glycemia relationship. These findings set the stage for future research into personalized lifestyle interventions integrating genetic insights with tailored dietary strategies to mitigate disease risk based on individual genetic profiles.
(© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
Databáze: MEDLINE
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