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

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 investigated links between blood DNA methylation and child height in four LMIC cohorts (n=1927) and identified a robust association at three CpGs in the suppressor of cytokine signalling 3 (SOCS3) gene which replicated in a high-income country cohort (n=879).SOCS3methylation (SOCS3m) – height associations were independent of genetic effects. Mendelian randomization analysis confirmed a causal effect ofSOCS3mon height. In longitudinal analysis in a LMIC cohortSOCS3mexplained a maximum 9.5% of height variance in mid-childhood while the variance explained by height polygenic risk score increased from birth to 21 years (2% to 18%). Children'sSOCS3mwas associated with prenatal maternal folate and socio-economic status. In-vitro characterization confirmed a regulatory effect ofSOCS3mon gene expression. Our findings suggest that epigenetic modifications may play an important role in driving child height in LMIC.

Placental chorionic plate DNA methylation patterns correlate with DNA methylation at SOCS3 in newborn human peripheral blood cells

“…2). Methylation at cg18181703 correlated with child height in different socioeconomic cohorts and exerted causal effects on height [33].…”