TREM2 has a significant, gender-specific, effect on human obesity

Abstract

Abstract Triggering Receptor Expressed On Myeloid Cells 2 (TREM2) is a membrane protein expressed on immune cells, involved in neurodegenerative diseases and cancer. Recently, it was shown that TREM2 is expressed on lipid associated macrophages in adipose tissue, and that TREM2 knockout mice suffer from metabolic symptoms. Here, a computational study using public databases, brings direct evidence for the involvement of TREM2 in human obesity. First, we show a significant correlation between TREM2 expression levels and BMI in adipose tissues in samples from the GTEx database. This association was evident for males but not for females. Second, we identified in the UK Biobank cohort a coding SNP in TREM2 with a significant effect on BMI. Compared to previously identified SNPs associated with BMI, this SNP (rs2234256 SNP, L211P) has the strongest association, reflected in significantly higher BMI values of people carrying the SNP as heterozygous and even more for homozygous. Strikingly, this association was evident only for females. These observations suggest a novel gender-specific role of TREM2 in human obesity, and call for further studies to elucidate the mechanism by which this gene correlates with an obese phenotype.