Twin birth changes DNA methylation of subsequent siblings

Shuai Li; Eunae Kim; Ee Ming Wong; Ji-Hoon Eric Joo; Tuong L Nguyen; Jennifer Stone; Yun-Mi Song; Louisa B Flander; Richard Saffery; Graham G Giles; Melissa C Southey; Joohon Sung; John L Hopper

doi:10.1038/s41598-017-08595-6

Twin birth changes DNA methylation of subsequent siblings

Sci Rep. 2017 Aug 16;7(1):8463. doi: 10.1038/s41598-017-08595-6.

Authors

Shuai Li¹, Eunae Kim², Ee Ming Wong³, Ji-Hoon Eric Joo³, Tuong L Nguyen¹, Jennifer Stone⁴, Yun-Mi Song⁵, Louisa B Flander¹, Richard Saffery^{6

7}, Graham G Giles^{1

8}, Melissa C Southey³, Joohon Sung^{2

9}, John L Hopper^{10

11

12}

Affiliations

¹ Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, Victoria, Australia.
² Department of Epidemiology, School of Public Health, Seoul National University, Seoul, South Korea.
³ Genetic Epidemiology Laboratory, Department of Pathology, University of Melbourne, Parkville, Victoria, Australia.
⁴ Centre for Genetic Origins of Health and Disease, Curtin University and the University of Western Australia, Perth, Western Australia, Australia.
⁵ Department of Family Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
⁶ Murdoch Childrens Research Institute, Royal Children's Hospital, Parkville, Victoria, Australia.
⁷ Department of Paediatrics, University of Melbourne, Parkville, Victoria, Australia.
⁸ Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Victoria, Australia.
⁹ Institute of Health and Environment, Seoul National University, Seoul, South Korea.
¹⁰ Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, Victoria, Australia. j.hopper@unimelb.edu.au.
¹¹ Department of Epidemiology, School of Public Health, Seoul National University, Seoul, South Korea. j.hopper@unimelb.edu.au.
¹² Institute of Health and Environment, Seoul National University, Seoul, South Korea. j.hopper@unimelb.edu.au.

Abstract

We asked if twin birth influences the DNA methylation of subsequent siblings. We measured whole blood methylation using the HumanMethylation450 array for siblings from two twin and family studies in Australia and Korea. We compared the means and correlations in methylation between pairs of siblings born before a twin birth (BT siblings), born on either side of a twin birth (B/AT pairs) and born after a twin birth (AT siblings). For the genome-wide average DNA methylation, the correlation for AT pairs (r_AT) was larger than the correlation for BT pairs (r_BT) in both studies, and from the meta-analysis, r_AT = 0.46 (95% CI: 0.26, 0.63) and r_BT = -0.003 (95% CI: -0.30, 0.29) (P = 0.02). B/AT pairs were not correlated (from the meta-analysis r_BAT = 0.08; 95% CI: -0.31, 0.45). Similar results were found for the average methylation of several genomic regions, e.g., CpG shelf and gene body. BT and AT pairs were differentially correlated in methylation for 15 probes (all P < 10^-7), and the top 152 differentially correlated probes (at P < 10^-4) were enriched in cell signalling and breast cancer regulation pathways. Our observations are consistent with a twin birth changing the intrauterine environment such that siblings both born after a twin birth are correlated in DNA methylation.

Publication types

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

MeSH terms

Adult
Aged
Australia
Birth Order
CpG Islands / genetics
DNA Methylation*
Female
Genome, Human / genetics
Humans
Male
Middle Aged
Pregnancy
Pregnancy, Twin / genetics*
Republic of Korea
Siblings*
Twins / genetics*