Dataset Information

Association of CREBRF variants with obesity and diabetes in Pacific Islanders from Guam and Saipan.

ABSTRACT: AIMS/HYPOTHESIS:Variants in CREBRF (rs12513649 and rs373863828) have been strongly associated with increased BMI and decreased risk of type 2 diabetes in Polynesian populations; the A allele at rs373863828 is common in Polynesians but rare in most other global populations. The aim of the present study was to assess the association of CREBRF variants with obesity and diabetes in Pacific Islander (largely Marianas and Micronesian) populations from Guam and Saipan. METHODS:CREBRF rs12513649 and rs373863828 were genotyped in 2022 participants in a community-based cross-sectional study designed to identify determinants of diabetes and end-stage renal disease (ESRD). Associations were analysed with adjustment for age, sex, ESRD and the first four genetic principal components from a genome-wide association study (to account for population stratification); a genomic control procedure was used to account for residual stratification. RESULTS:The G allele at rs12513649 had an overall frequency of 7.7%, which varied from 2.2% to 20.7% across different Marianas and Micronesian populations; overall frequency of the A allele at rs373863828 was 4.2% (range: 1.1-5.4%). The G allele at rs12513649 was associated with higher BMI (??=?1.55 kg/m2 per copy; p?=?0.0026) as was the A allele at rs373863828 (??=?1.48 kg/m2, p?=?0.033). The same alleles were associated with lower risk of diabetes (OR per copy: 0.63 [p?=?0.0063] and 0.49 [p?=?0.0022], respectively). Meta-analyses combining the current results with previous results in Polynesians showed a strong association between the A allele at rs373863828 and BMI (??=?1.38 kg/m2; p?=?2.5?×?10-29) and diabetes (OR 0.65, p?=?1.5?×?10-13). CONCLUSIONS/INTERPRETATION:These results confirm the associations of CREBRF variants with higher BMI and lower risk of diabetes and, importantly, they suggest that these variants contribute to the risk of obesity and diabetes in Oceanic populations.

SUBMITTER: Hanson RL

PROVIDER: S-EPMC6721609 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Association of CREBRF variants with obesity and diabetes in Pacific Islanders from Guam and Saipan.

Hanson Robert L RL Safabakhsh Saied S Curtis Jeffrey M JM Hsueh Wen-Chi WC Jones Lois I LI Aflague Tanisha F TF Duenas Sarmiento Jenny J Kumar Satish S Blackburn Nicholas B NB Curran Joanne E JE Mahkee Darin D Baier Leslie J LJ Knowler William C WC Nelson Robert G RG

Diabetologia 20190706 9

<h4>Aims/hypothesis</h4>Variants in CREBRF (rs12513649 and rs373863828) have been strongly associated with increased BMI and decreased risk of type 2 diabetes in Polynesian populations; the A allele at rs373863828 is common in Polynesians but rare in most other global populations. The aim of the present study was to assess the association of CREBRF variants with obesity and diabetes in Pacific Islander (largely Marianas and Micronesian) populations from Guam and Saipan.<h4>Methods</h4>CREBRF rs1 ...[more]

PMID: 31280340

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Project description:BackgroundMāori and Pacific Islander people are a priority population originating from Australasia. Māori and Pacific Islander children exhibit greater risk of obesity and associated morbidities compared to children of other descent, secondary to unique cultural practices and socioeconomic disadvantage. Despite these known risk factors, there is limited synthesised evidence for preventing and treating childhood obesity in this unique population. The objective of this systematic review was to identify and evaluate global prevention or treatment interventions for overweight or obesity that targeted Māori and Pacific Islander children and adolescents (aged 2-17 years).MethodsThe Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. The databases PubMed, EMBASE, Scopus, Web of Science and CINAHL were searched from inception to August 2018. Study quality and risk of bias was assessed using a modified Downs and Black Quality Checklist for Health Care Intervention Studies. Studies were included if RCT/intervention/case control/ or prevention study designs. The study group was defined under the search term 'Oceanic Ancestry Group'.ResultsOf the initial 94 articles identified, six were included describing two prevention and three treatment interventions. Interventions were heterogenous in setting, design, length and outcomes. Four interventions were implemented in New Zealand. Most studies were of 'fair' quality. One study recruited an exclusive population of Māori and Pacific Islander participants. In the five studies that recruited mixed populations, one performed sub-group analysis on Māori and Pacific Islander participants. No study reported an improvement in anthropometric outcomes post-intervention in complete or sub-group analysis. Improvements in cardiometabolic or psychological secondary outcomes were inconsistent across all studies.ConclusionsThere is a lack of evidence to recommend specific intervention characteristics to optimise obesity prevention or treatment outcomes for Māori and Pacific Islander children. Future research requires greater consideration of cultural values and beliefs, community engagement, exclusive targeting of Māori and Pacific Islander children and families, and sub-group analyses for mixed-population studies. Incorporating co-design principles during study design and implementation can maximise the cultural specificity of interventions and may contribute to improved health and weight-related outcomes for this at-risk, priority population.Trial registrationPROSPERO CRD42019121790 (26 March 2019).

Project description:Human genetic diversity in the Pacific has not been adequately sampled, particularly in Melanesia. As a result, population relationships there have been open to debate. A genome scan of autosomal markers (687 microsatellites and 203 insertions/deletions) on 952 individuals from 41 Pacific populations now provides the basis for understanding the remarkable nature of Melanesian variation, and for a more accurate comparison of these Pacific populations with previously studied groups from other regions. It also shows how textured human population variation can be in particular circumstances. Genetic diversity within individual Pacific populations is shown to be very low, while differentiation among Melanesian groups is high. Melanesian differentiation varies not only between islands, but also by island size and topographical complexity. The greatest distinctions are among the isolated groups in large island interiors, which are also the most internally homogeneous. The pattern loosely tracks language distinctions. Papuan-speaking groups are the most differentiated, and Austronesian or Oceanic-speaking groups, which tend to live along the coastlines, are more intermixed. A small "Austronesian" genetic signature (always <20%) was detected in less than half the Melanesian groups that speak Austronesian languages, and is entirely lacking in Papuan-speaking groups. Although the Polynesians are also distinctive, they tend to cluster with Micronesians, Taiwan Aborigines, and East Asians, and not Melanesians. These findings contribute to a resolution to the debates over Polynesian origins and their past interactions with Melanesians. With regard to genetics, the earlier studies had heavily relied on the evidence from single locus mitochondrial DNA or Y chromosome variation. Neither of these provided an unequivocal signal of phylogenetic relations or population intermixture proportions in the Pacific. Our analysis indicates the ancestors of Polynesians moved through Melanesia relatively rapidly and only intermixed to a very modest degree with the indigenous populations there.

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Dataset Information

Association of CREBRF variants with obesity and diabetes in Pacific Islanders from Guam and Saipan.

Publications

Association of CREBRF variants with obesity and diabetes in Pacific Islanders from Guam and Saipan.

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