A missense variant in CREBRF is associated with taller stature in Samoans.
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ABSTRACT: Objectives
Studies have demonstrated that rs373863828, a missense variant in CREBRF, is associated with a number of anthropometric traits including body mass index (BMI), obesity, percent body fat, hip circumference, and abdominal circumference. Given the biological relationship between height and adiposity, we hypothesized that the effect of this variant on BMI might be due in part to an association of this variant with height.Methods
We tested the hypothesis that minor allele of rs373863828 is associated with height in a Samoan population in two adult cohorts and in a separate cohort of children (age 5-18 years old) using linear mixed modeling.Results
We found evidence of a strong relationship between rs373863828 and greater mean height in Samoan adults (0.77 cm greater average height for each copy of the minor allele) with the same direction of effect in Samoan children.Conclusions
These results suggest that the missense variant rs373863828 in CREBRF, first identified through an association with larger BMI, may be related to an underlying biological mechanism affecting overall body size including stature.
SUBMITTER: Carlson JC
PROVIDER: S-EPMC7501196 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ObjectiveA missense variant, rs373863828, in CREBRF is associated with obesity in Polynesians. We investigate whether rs373863828 and other factors are associated with body mass index (BMI) rate-of-change between 2010 and 2017-19 in Samoans.MethodsWe used sex-stratified models to test whether BMI rate-of-change was associated with rs373863828, baseline BMI, age, residence, physical activity, and household asset score in a cohort study of 480 Samoan adults measured in both 2010 (mean age 43.8 years) and 2017-19.ResultsMean BMI increased from 32.1 to 33.5 kg/m2 in males (n = 220, p = 1.3 ×10-8) and from 35.9 to 37.8 kg/m2 in females (n = 260, p = 1.2 ×10-13). In females, the A allele was associated with a higher rate-of-change (0.150 kg/m2/year/allele, p = 1.7 ×10-4). Across 10-year age groups, mean BMI rate-of-change was lower in older participants. The BMI rate of change differed by genotype: it was, in females with AA genotype, approximately half that seen in GG and AG participants. In females lower baseline household asset scores were associated with a higher rate-of-change (p = 0.002).ConclusionsIn Samoans, the minor A allele of rs373863828 is associated with an increased rate-of-change in BMI in females. On average, BMI of females with the AA genotype increased 0.30 kg/m2/year more than of those with the GG genotype.
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