Work

Exome Sequencing of 21 Bardet‐Biedl Syndrome (BBS) Genes to Identify Obesity Variants in 6,851 American Indians

Year: 2021

Type: article

Abstract: OBJECTIVE: In an ongoing effort to identify the genetic variation that contributes to obesity in American Indians, known Bardet-Biedl syndrome (BBS) genes were analyzed for an effect on BMI and leptin signaling. METHODS: Potentially deleterious variants (Combined Annotation Dependent Depletion score > 20) in BBS genes were identified in whole-exome sequence data from 6,851 American Indians informative for BMI. Common variants (detected in ≥ 10 individuals) were analyzed for association with BMI; rare variants (detected in < 10 individuals) were analyzed for mean BMI of carriers. Functional assessment of variants' effect on signal transducer and activator of transcription 3 (STAT3) activity was performed in vitro. RESULTS: ), four were in BBS9. In vitro analysis of BBS9 found the Ile allele at Thr549Ile had a 20% increase in STAT3 activity compared with the Thr allele (P = 0.01). Western blot analysis showed the Ile allele had a 15% increase in STAT3 phosphorylation (P = 0.006). Comparable functional results were observed with Ser545Gly and Val209Leu but not Leu665Phe and Lys810Glu. CONCLUSIONS: Potentially functional variants in BBS genes in American Indians are reported. However, functional evidence supporting a causal role for BBS9 in obesity is inconclusive.

Source: Obesity

DOI: 10.1002/oby.23115