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DNA methylation at the suppressor of cytokine signaling 3 (SOCS3) gene influences height in childhood.

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Arumalla, Manisha 
Nongmaithem, Suraj S  ORCID logo
Sankareswaran, Alagu  ORCID logo


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.



Female, Pregnancy, Humans, Child, DNA Methylation, Suppressor of Cytokine Signaling Proteins, Epigenesis, Genetic, Epigenomics, Cytokines, Suppressor of Cytokine Signaling 3 Protein

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Nat Commun

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Springer Science and Business Media LLC
Medical Research Council (MC_U123261351)
Medical Research Council (MC_U105960371)