Samoans are a unique founder population with a high prevalence of obesity1–3, making them well suited for identifying new genetic contributors to obesity4. We conducted a genome-wide association study (GWAS) in 3,072 Samoans, discovered a variant, rs12513649, strongly associated with body mass index (BMI) (P = 5.3 × 10−14), and replicated the association in 2,102 additional Samoans (P = 1.2 × 10−9). Targeted sequencing identified a strongly associated missense variant, rs373863828 (p.Arg457Gln), in CREBRF (meta P = 1.4 × 10−20). Although this variant is extremely rare in other populations, it is common in Samoans (frequency of 0.259), with an effect size much larger than that of any other known common BMI risk variant (1.36–1.45 kg/m2 per copy of the risk-associated allele). In comparison to wild-type CREBRF, the Arg457Gln variant when overexpressed selectively decreased energy use and increased fat storage in an adipocyte cell model. These data, in combination with evidence of positive selection of the allele encoding p.Arg457Gln, support a ‘thrifty’ variant hypothesis as a factor in human obesity.

Non-communicable diseases (NCDs) now account for more than 36 million deaths each year; many of which are premature. Pacific Islanders are some of the worst afflicted by obesity and diabetes with prevalence of both diseases rising disproportionately faster in the Pacific region over the past three decades than in the rest of the world. A high burden of disease is also found among enclaves of Pacifican migrants in the USA, Australia, and New Zealand. Urgent action is needed to alleviate the high economic and personal costs now associated with NCDs in Pacific Islanders. In this article, we describe contributors to the temporal trends in obesity and diabetes, discuss the current burden of disease in the Pacific Islands and among migrant communities, and suggest priorities for future research in this area. Finally, we discuss challenges unique to intervention among Pacific Islanders and highlight promising opportunities to reduce the NCD burden.

Objective To describe the prevalence of obesity-related noncommunicable diseases (NCDs) and associated risk factors in a sample of Samoan adults studied in 2010 as part of a genome-wide assocation study (GWAS) for obesity related traits. Methods Anthropometric and biochemical data collected from n = 3,475 participants (n = 1,437 male; n = 2,038 female) aged 24.5 to <65 years were used to describe the prevalence of obesity, diabetes, hypertension, and dyslipidemia within the study sample. One way analysis of variance, χ2 tests, and binary logistic regression were used to identify differences in disease and risk factor prevalence by 10-year age group, gender, or by census region of residence. Results Obesity was highly prevalent among the study sample; 64.6% of females and 41.2% of males were obese according to Polynesian cutoffs (BMI ≥ 32 kg/m2). Females were less likely than males to have hypertension (31.7% vs. 36.7%) but equally likely to have diabetes (17.8% vs. 16.4%). With the exception of obesity and low HDL-cholesterol in females only, there were significant differences in the prevalence of all NCDs and associated risk factors by age group, with the oldest age group (55 to <65 years) most affected. In both sexes, residents of the Apia Urban Area were at significantly greater risk of obesity, diabetes, low HDL-cholesterol, and high triglycerides than residents of the more rural Savaii region. Conclusions The phenotypic characteristics of this sample provide evidence of a continuation of previously reported temporal trends toward obesity and its associated disorders. Attention must be paid to the critical NCD situation in Samoa.