DNA methylome profiling in identical twin pairs discordant for body mass index

• Published in: International Journal of Obesity Vol. 43; no. 12; pp. 2491 - 2499
• Main Authors: Li, Weilong, Zhang, Dongfeng, Wang, Weijing, Wu, Yili, Mohammadnejad, Afsaneh, Lund, Jesper, Baumbach, Jan, Christiansen, Lene, Tan, Qihua
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.12.2019; Nature Publishing Group
• Subjects: 38/43; 692/308/174; 692/699/75; 692/700/478/174; Adipose tissue; Adult; Aged; Analysis; Bisulfite; Blood cells; Body Mass Index; Body size; Deoxyribonucleic acid; Discordance; DNA; DNA fingerprinting; DNA methylation; DNA Methylation - genetics; DNA sequencing; Epidemiology; Epigenesis, Genetic - genetics; Epigenetic inheritance; Epigenetics; Epigenome - genetics; Epigenomics; Female; Gene expression; Genes; Genetic aspects; Genetic diversity; Genetic factors; Genetic variance; Genomes; Genomics; Health Promotion and Disease Prevention; Heritability; Humans; Internal Medicine; Male; Medicine; Medicine & Public Health; Metabolic Diseases; Methylation; Middle Aged; Obesity; Obesity - genetics; Public Health; Sulfites; Twins; Twins, Monozygotic - genetics; Type 2 diabetes; Denmark
• ISSN: 0307-0565; 1476-5497; 1476-5497
• DOI: 10.1038/s41366-019-0382-4

Objective Body mass index (BMI) serves as an important measurement of obesity and adiposity, which are highly correlated with cardiometabolic diseases. Although high heritability has been estimated, the identified genetic variants by genetic association studies only explain a small proportion of BMI variation. As an active effort for further exploring the molecular basis of BMI variation, large-scale epigenome-wide association studies have been conducted but with limited number of loci reported, perhaps due to poorly controlled confounding factors, including genetic factors. Being genetically identical, monozygotic twins discordant for BMI are ideal subjects for analyzing the epigenetic association between DNA methylation and BMI, providing perfect control on their genetic makeups largely responsible for BMI variation. Subjects We performed an epigenome-wide association study on BMI using 30 identical twin pairs (15 male and 15 female pairs) with age ranging from 39 to 72 years and degree of BMI discordance ranging from 3–7.5 kg/m 2 . Methylation data from whole blood samples were collected using the reduced representation bisulfite sequencing technique. Results After adjusting for blood cell composition and clinical variables, we identified 136 CpGs with p -value < 1e-4, 30 CpGs with p  < 1e-05 but no CpGs reached genome-wide significance. Genomic region-based analysis found 11 differentially methylated regions harboring coding and non-coding genes some of which were validated by gene expression analysis on independent samples. Conclusions Our DNA methylation sequencing analysis on identical twins provides new references for the epigenetic regulation on BMI and obesity.