"Soifua Manuia" (Good Health) Study (Samoa)
Samoans are a unique founder population with a high prevalence of obesity. In a genome-wide association study (GWAS) with 3,500 participants conducted in Samoa in 2010 we discovered a novel missense variant (rs373863828) that was associated with increased body mass index in this population (Minster et al., 2016). This variant is suspected to be ‘thrifty’, promoting a unique pattern of energy conservation and use among individuals who have the risk variant.
Around 45% of Samoans have the risk variant, so understanding the mechanisms by which it increases someone’s risk of obesity will be important to determine how best to intervene. This new study will re-recruit 500 of the original GWAS participants based on the presence or absence of the Samoan missense mutation to explore the function of variant in more depth.
Participants will receive a dual-energy X-ray absorptiometry (DXA) scan to measure their body composition, an oral glucose tolerance test to observe insulin response to a glucose load, and wear accelerometers for seven days to objectively measure physical activity as well as completing a number of questionnaires and cognitive tasks designed to measure factors related to health, dietary intake, and weight.
Timeline: This study will be actively recruiting participants between June 2017 and December 2018 in Apia, Samoa
Investigators: Nicola Hawley, Stephen McGarvey (Brown University [grant PI]), Daniel Weeks, Ryan Minster, Erin Kershaw, Zsolt Urban (all University of Pittsburgh), Ranjan Deka (Cincinnati)
Funding Source: National Institutes of Health, National Heart Lung and Blood Institute 2R01HL093093
Affiliated Students: Rebecca Valderrama (Yale, MPH Candidate)
If you can not access any of the full publications, please reach out to Nicola Hawley
1. A thrifty variant in CREBRF strongly influences body mass index in Samoans.
Minster R.L.*, Hawley N.L.*, Su, C., Sun, G., Kershaw E.E., Chen, H., Buhule, O.D., Lin, J., Reupena, M.S., Naseri, T., Urban, Z., Deka, R., Weeks, D.E. & McGarvey, S.T. (2016) Nature Genetics 48 (9): 1049-54. *Co-First Authors. https://pubmed.ncbi.nlm.nih.gov/27455349/
This study conducted a genome-wide association study in 3,072 Samoans and discovered a variant, rs12513649, strongly associated with BMI. We replicated this association in another 2,102 Samoans and identified a strongly associated missense variant, rs373863828, in CREBRF. The variant is rare in other populations but is common in Samoans, and in comparison to the wild-type CREBRF, shows decreased energy use and increased fat storage in adipocyte cells. The findings from the data, alongside evidence of positive selection of the allele encoding the missense variant, support a thrifty' variant hypothesis as a factor in human obesity.
2. Genome-wide association study of adiposity in Samoans: Prevalence of non-communicable disease and associated risk factors.
Hawley, N.L., Minster, R.L., Weeks, D.E., Viali, S., Reupena, M.S., Deka, R., & McGarvey, S.T. (2014) American Journal of Human Biology 26: 491-501. https://pubmed.ncbi.nlm.nih.gov/24799123/
This study described the prevalence of obesity-related noncommunicable diseases and associated risk factors in a sample of 3,475 Samoan adults aged 24 to <65 as part of a genome-wide association study for obesity-related traits. Findings show that obesity was highly prevalent in the sample studied—64.6% of females and 41.2% of males were obese according to Polynesian cutoffs—and also address the prevalence of diabetes, hypertension and dyslipidemia. The study concludes phenotypic characteristics of this sample provide further evidence previously reported trends toward obesity and its associated disorders.
3. Cardiovascular disease risk factors and DNA methylation at the LINE-1 repeat region in peripheral blood from Samoan Islanders.
Cash, H., McGarvey, S.T., Housemann, E.A., Marsit, C.J., Hawley, N.L., Lambert-Messerlian, G.M., Viali, S., Tuitele, J. & Kelsey, K.T. (2011) Epigenetics 6 (10): 1257-1264 https://pubmed.ncbi.nlm.nih.gov/21937883/
We sequenced DNA in peripheral blood samples from men and women in American Samoa and Samoa to study the relationship between LINE-1 methylation and factors associated with cardiovascular and metabolic diseases, like LDL and HDL. The findings confirm that DNA “global” loss of methylation, which was previously observed in cardiovascular disease, is associated with altered levels of HDL and LDL, and indicate the need for further research in understanding the relationship between LINE-1 methylation and risk factors for cardiovascular disease.
4. Nonmydriatic fundus photography in a high-risk population of Samoans with diabetes: the Soifua Manuia Eye Screening Program.
LaMonica, L., Hawley, N.L., Bhardwaj, M., Naseri, T., Reupena, M.S. & Ramsey, D. (2019). Clinical and Experimental Ophthalmology 47 (7): 954-956. https://pubmed.ncbi.nlm.nih.gov/31034672/
In this study, the research team piloted a low‐cost, smartphone‐based remote retinal diagnosis system to screen for diabetic retinopathy in a high‐risk population of Samoans with diabetes and elevated blood glucose levels. Their objective was to determine the percentage of radable images that could be obtained using the PanOptic iExaminer System. This study was undertaken alongside an ongoing longitudinal study of the genetics of obesity and diabetes among Samoans, the Soifua Manuia (“Good Health”) study, and 206 of the approximately 700 adults in the overall study partook. A total of 393 eyes, or 95.4%, from these 206 participants were successfully imaged using the PanOptic iExaminer. The researchers found that clinically useful fundus images could be successfully obtained in the majority of participants and that the durability and maintainability of the PanOptic iExaminer System in the field proves promising as a cost‐effective device for use in low‐ to middle‐income countries.
Adia, A.C., Hawley, N.L., Naseri, T., Reupena, M.S. & McGarvey, S.T. Tobacco Prevention and Cessation (in press). http://www.tobaccopreventioncessation.com/Tobacco-smoking-patterns-in-Samoa-in-2010-Implications-for-ninterventions,114093,0,2.html
In this study, the researchers describe current smoking and daily tobacco use in adults from Samoa, with a focus on sex and age stratified analyses of the influence of occupation, education, census region, household asset ownership, and alcohol use in order to help develop targeted interventions. The nationwide survey included 3745 adults, aged 25–65 years from 33 villages, and was completed in Samoa in 2010. Interviews were used to assess current smoking status, daily tobacco use, current alcohol use, and a variety of sociodemographic factors. The team found that more than half of men, or 51.3%, and 21.8% of women were current tobacco users. On average, men and women smoked on average 10.9 and 8.7 cigarettes each day, respectively. In men, being married, a subsistence farmer/laborer, an alcohol user, and having low household assets were all independently associated with being a tobacco smoker. In women, not completely secondary education, being 25–34 years old, residing in urban atypia, and being an alcohol user were all independently associated with being a tobacco smoker. The researchers conclude that the high rates of tobacco usage in Samoa warrant the development of interventions for cessation that are specific to sex, age, education, and household socioeconomic status.