Can I read Variant-to-function analysis of the childhood obesity chr12q13 locus implicates rs7132908 as a causal variant within the 3’ UTR of FAIM2 on EtoBox?

Variant-to-function analysis of the childhood obesity chr12q13 locus implicates rs7132908 as a causal variant within the 3’ UTR of FAIM2 by Sheridan H. Littleton; Khanh B. Trang; Christina M. Volpe; Kieona Cook; Nicole DeBruyne; Jean Ann Maguire; Mary Ann Weidekamp; Keith Boehm; Alessandra Chesi; James A. Pippin; Stewart A. Anderson; Andrew D. Wells; Matthew C. Pahl; Struan F.A. Grant is a scholarly article available to read on EtoBox.

What is Variant-to-function analysis of the childhood obesity chr12q13 locus implicates rs7132908 as a causal variant within the 3’ UTR of FAIM2 about?

## SUMMARY The ch12q13 obesity locus is among the most significant childhood obesity loci identified in genome-wide association studies. This locus resides in a non-coding region within __FAIM2__; thus, the underlying causal variant(s) presumably influence disease susceptibility via an influence on __cis__-regulation within the genomic region. We implicated rs7132908 as a putative causal variant at this locus leveraging a combination of our inhouse 3D genomic data, public domain datasets, and several computational approaches. Using a luciferase reporter assay in human primary astrocytes, we observed allele-specific __cis__-regulatory activity of the immediate region harboring rs7132908. Motivated by this finding, we went on to generate isogenic human embryonic stem cell lines homozygous for either rs7132908 allele with CRISPR-Cas9 homology-directed repair to assess changes in gene expression due to genotype and chromatin accessibility throughout a differentiation to hypothalamic neurons, a key cell type known to regulate feeding behavior. We observed that the rs7132908 obesity risk allele influenced the expression of __FAIM2__ along with other genes, decreased the proportion of neu

Author

Sheridan H. Littleton; Khanh B. Trang; Christina M. Volpe; Kieona Cook; Nicole DeBruyne; Jean Ann Maguire; Mary Ann Weidekamp; Keith Boehm; Alessandra Chesi; James A. Pippin; Stewart A. Anderson; Andrew D. Wells; Matthew C. Pahl; Struan F.A. Grant

Publisher

Cold Spring Harbor Laboratory

Published

2023