PMID- 37184252
OWN - NLM
STAT- MEDLINE
DCOM- 20230809
LR  - 20230810
IS  - 1460-2083 (Electronic)
IS  - 0964-6906 (Linking)
VI  - 32
IP  - 16
DP  - 2023 Aug 7
TI  - Epigenome-wide methylation study identified two novel CpGs associated with T2DM 
      risk and a network of co-methylated CpGs capable of patient's classifications.
PG  - 2576-2586
LID - 10.1093/hmg/ddad084 [doi]
AB  - Prevention of Type 2 diabetes mellitus (T2DM) pandemic needs markers that can 
      precisely predict the disease risk in an individual. Alterations in DNA 
      methylations due to exposure towards environmental risk factors are widely sought 
      markers for T2DM risk prediction. To identify such individual DNA methylation 
      signatures and their effect on disease risk, we performed an epigenome-wide 
      association study (EWAS) in 844 Indian individuals of Indo-European origin. We 
      identified and validated methylation alterations at two novel CpG sites in 
      MIR1287 (cg01178710) and EDN2-SCMH1 (cg04673737) genes associated with T2DM risk 
      at the epigenome-wide-significance-level (P < 1.2 x 10-7). Further, we also 
      replicated the association of two known CpG sites in TXNIP, and CPT1A in the 
      Indian population. With 535 EWAS significant CpGs (P < 1.2 x 10-7) identified in 
      the discovery phase samples, we created a co-methylation network using weighted 
      correlation network analysis and identified four modules among the CpGs. We 
      observed that methylation of one of the module associates with T2DM risk factors 
      (e.g. BMI, insulin and C-peptide) and can be used as markers to segregate T2DM 
      patients with good glycemic control (e.g. low HbA1c) and dyslipidemia (low HDL 
      and high TG) from the other patients. Additionally, an intronic SNP (rs6503650) 
      in the JUP gene, a member of the same module, associated with methylation at all 
      the 14 hub CpG sites of that module as methQTL. Our network-assisted EWAS is the 
      first to systematically explore DNA methylation variations conferring risks to 
      T2DM in Indians and use the identified risk CpG sites for patient segregation 
      with different clinical outcomes. These findings can be useful for better 
      stratification of patients to improve the clinical management and treatment 
      effects.
CI  - (c) The Author(s) 2023. Published by Oxford University Press. All rights reserved. 
      For Permissions, please email: journals.permissions@oup.com.
FAU - Giri, Anil K
AU  - Giri AK
AD  - Genomics and Molecular Medicine Unit, CSIR-Institute of Genomics and Integrative 
      Biology, New Delhi 110025, India.
AD  - Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India.
FAU - Prasad, Gauri
AU  - Prasad G
AD  - Genomics and Molecular Medicine Unit, CSIR-Institute of Genomics and Integrative 
      Biology, New Delhi 110025, India.
AD  - Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India.
FAU - Parekatt, Vaisak
AU  - Parekatt V
AD  - Genomics and Molecular Medicine Unit, CSIR-Institute of Genomics and Integrative 
      Biology, New Delhi 110025, India.
FAU - Rajashekar, Donaka
AU  - Rajashekar D
AD  - Genomics and Molecular Medicine Unit, CSIR-Institute of Genomics and Integrative 
      Biology, New Delhi 110025, India.
FAU - Tandon, Nikhil
AU  - Tandon N
AD  - Department of Endocrinology and Metabolism, All India Institute of Medical 
      Sciences, New Delhi 110029, India.
FAU - Bharadwaj, Dwaipayan
AU  - Bharadwaj D
AUID- ORCID: 0000-0001-5268-8482
AD  - Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India.
AD  - Systems Genomics Laboratory, School of Biotechnology, Jawaharlal Nehru 
      University, New Delhi 110067, India.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Hum Mol Genet
JT  - Human molecular genetics
JID - 9208958
RN  - 0 (MIRN1287 microRNA, human)
RN  - 0 (MicroRNAs)
SB  - IM
MH  - Humans
MH  - Epigenome/genetics
MH  - Epigenesis, Genetic/genetics
MH  - *Diabetes Mellitus, Type 2/genetics
MH  - Genome-Wide Association Study
MH  - CpG Islands/genetics
MH  - DNA Methylation/genetics
MH  - *MicroRNAs
EDAT- 2023/05/15 13:06
MHDA- 2023/08/09 06:43
CRDT- 2023/05/15 09:03
PHST- 2022/09/02 00:00 [received]
PHST- 2023/04/24 00:00 [revised]
PHST- 2023/05/11 00:00 [accepted]
PHST- 2023/08/09 06:43 [medline]
PHST- 2023/05/15 13:06 [pubmed]
PHST- 2023/05/15 09:03 [entrez]
AID - 7162637 [pii]
AID - 10.1093/hmg/ddad084 [doi]
PST - ppublish
SO  - Hum Mol Genet. 2023 Aug 7;32(16):2576-2586. doi: 10.1093/hmg/ddad084.