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Functional variants in cytochrome b5 type A (CYB5A) are enriched in Southwest American Indian individuals and associate with obesity.
- Source :
-
Obesity (Silver Spring, Md.) [Obesity (Silver Spring)] 2022 Feb; Vol. 30 (2), pp. 546-552. Date of Electronic Publication: 2022 Jan 18. - Publication Year :
- 2022
-
Abstract
- Objective: This study aimed to identify genetic variants enriched in Southwest American Indian (SWAI) individuals that associate with BMI.<br />Methods: Whole genome sequencing data (n = 296) were used to identify potentially functional variants that are common in SWAI individuals (minor allele frequency ≥10%) but rare in other ethnic groups (minor allele frequency < 0.1%). Enriched variants were tested for association with BMI in 5,870 SWAI individuals. One variant was studied using a luciferase reporter, and haplotypes that included this variant were analyzed for association with various measures of obesity (n = 917-5,870), 24-hour energy expenditure (24-h EE; n = 419), and skeletal muscle biopsy expression data (n = 207).<br />Results: A 5' untranslated region variant in cytochrome b5 type A (CYB5A), rs548402150, met the enrichment criteria and associated with increased BMI (β = 2%, p = 0.004). Functionally, rs548402150 decreased luciferase expression by 30% (p = 0.003) and correlated with decreased skeletal muscle CYB5A expression (β = -0.5 SD, p = 0.0008). Combining rs548402150 with two splicing quantitative trait loci in CYB5A identified a haplotype carried almost exclusively in SWAI individuals that associated with increased BMI (β = 3%, p = 0.0003) and decreased CYB5A expression, whereas the most common haplotype in all ethnic groups associated with lower BMI and percentage of body fatness, increased 24-h EE, and increased CYB5A expression.<br />Conclusions: Further studies on the effects of CYB5A on 24-h EE and BMI may provide insights into obesity-related physiology.<br /> (Published 2022. This article is a U.S. Government work and is in the public domain in the USA. Obesity published by Wiley Periodicals LLC on behalf of The Obesity Society (TOS).)
Details
- Language :
- English
- ISSN :
- 1930-739X
- Volume :
- 30
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Obesity (Silver Spring, Md.)
- Publication Type :
- Academic Journal
- Accession number :
- 35043601
- Full Text :
- https://doi.org/10.1002/oby.23359