Genome wide association of methylation with BMI

A recent issue of The Lancet featured an epigenome wide association study (EWAS) of methylated CpGs associated with BMI. Sites were identified in an initial cohort of 479 Europeans and, after filtering data for false positives, inspected in a replication cohort of 339 people. Sites still significant were tested in a larger second replication cohort of 1789 individuals. Five sites were identified as significantly associated with BMI, three of which fall within the first intron of the gene HIF3A, which encodes a subunit of the Hypoxia Inducible Transcription Factor (HIF). Chromatin state at this intron indicates regulatory activity. For all these cases, increasing methylation is linearly correlated with increasing BMI. Notably, the association is tissue specific, manifesting in blood and adipose tissues, but not skin.