DNA methylation at the suppressor of cytokine signaling 3 (<i>SOCS3</i>) gene influences height in childhood

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Issarapu, Prachand, Arumalla, Manisha, Elliott, Hannah R, Nongmaithem, Suraj S, Sankareswaran, Alagu, Betts, Modupeh ORCID: 0000-0003-0083-7487, Sajjadi, Sara, Kessler, Noah J, Bayyana, Swati, Mansuri, Sohail R et al (show 15 more authors) , Derakhshan, Maria, Krishnaveni, GV, Shrestha, Smeeta, Kumaran, Kalyanaraman, Di Gravio, Chiara, Sahariah, Sirazul A, Sanderson, Eleanor, Relton, Caroline L, Ward, Kate A, Moore, Sophie E, Prentice, Andrew M, Lillycrop, Karen A, Fall, Caroline HD, Silver, Matt J and Chandak, Giriraj R (2023) DNA methylation at the suppressor of cytokine signaling 3 (<i>SOCS3</i>) gene influences height in childhood. NATURE COMMUNICATIONS, 14 (1). 5200-.

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Abstract

Human height is strongly influenced by genetics but the contribution of modifiable epigenetic factors is under-explored, particularly in low and middle-income countries (LMIC). We investigate links between blood DNA methylation and child height in four LMIC cohorts (n = 1927) and identify a robust association at three CpGs in the suppressor of cytokine signaling 3 (SOCS3) gene which replicates in a high-income country cohort (n = 879). SOCS3 methylation (SOCS3m)-height associations are independent of genetic effects. Mendelian randomization analysis confirms a causal effect of SOCS3m on height. In longitudinal analysis, SOCS3m explains a maximum 9.5% of height variance in mid-childhood while the variance explained by height polygenic risk score increases from birth to 21 years. Children's SOCS3m is associated with prenatal maternal folate and socio-economic status. In-vitro characterization confirms a regulatory effect of SOCS3m on gene expression. Our findings suggest epigenetic modifications may play an important role in driving child height in LMIC.

Item Type:	Article
Uncontrolled Keywords:	EMPHASIS study group, Humans, Cytokines, DNA Methylation, Epigenesis, Genetic, Pregnancy, Child, Female, Suppressor of Cytokine Signaling Proteins, Epigenomics, Suppressor of Cytokine Signaling 3 Protein
Divisions:	Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Infection, Veterinary and Ecological Sciences
Depositing User:	Symplectic Admin
Date Deposited:	30 Jan 2024 11:02
Last Modified:	30 Jan 2024 11:34
DOI:	10.1038/s41467-023-40607-0
Open Access URL:	https://doi.org/10.1038/s41467-023-40607-0
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3178124