Multivariate analysis of a missense variant in CREBRF reveals associations with measures of adiposity in people of Polynesian ancestries

Genet Epidemiol. 2023 Feb;47(1):105-118. doi: 10.1002/gepi.22508. Epub 2022 Nov 9.

Abstract

The minor allele of rs373863828, a missense variant in CREB3 Regulatory Factor, is associated with several cardiometabolic phenotypes in Polynesian peoples. To better understand the variant, we tested the association of rs373863828 with a panel of correlated phenotypes (body mass index [BMI], weight, height, HDL cholesterol, triglycerides, and total cholesterol) using multivariate Bayesian association and network analyses in a Samoa cohort (n = 1632), Aotearoa New Zealand cohort (n = 1419), and combined cohort (n = 2976). An expanded set of phenotypes (adding estimated fat and fat-free mass, abdominal circumference, hip circumference, and abdominal-hip ratio) was tested in the Samoa cohort (n = 1496). In the Samoa cohort, we observed significant associations (log10 Bayes Factor [BF] ≥ 5.0) between rs373863828 and the overall phenotype panel (8.81), weight (8.30), and BMI (6.42). In the Aotearoa New Zealand cohort, we observed suggestive associations (1.5 < log10 BF < 5) between rs373863828 and the overall phenotype panel (4.60), weight (3.27), and BMI (1.80). In the combined cohort, we observed concordant signals with larger log10 BFs. In the Samoa-specific expanded phenotype analyses, we also observed significant associations between rs373863828 and fat mass (5.65), abdominal circumference (5.34), and hip circumference (5.09). Bayesian networks provided evidence for a direct association of rs373863828 with weight and indirect associations with height and BMI.

Keywords: Bayesian association analyses; Bayesian network analyses; Māori; Pacific Islander; Samoan.

MeSH terms

  • Adiposity*
  • Bayes Theorem
  • Body Mass Index
  • Humans
  • Multivariate Analysis
  • Mutation, Missense
  • Obesity / genetics
  • Pacific Island People*
  • Tumor Suppressor Proteins* / genetics

Substances

  • CREB3 regulatory factor, human
  • Tumor Suppressor Proteins