Skip to Main Content

"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)

Relevant Publications:

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.

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.

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

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.

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.

5. The Household Water InSecurity Experiences (HWISE) Scale: development and validation of a household water insecurity measure using data from 23 low- and middle-income countries.

Young, S.L., Collins, S.M., Boateng, G.O., Neilands, T.B., Jamaluddine, Z., Miller, J.D., Brewis, A., Frongillo, E.A., Jepson, W.E., Melgar-Quinonez, H., Schuster, R.C., Stoler, J., Wutich, A. & HWISE Consortium Authors. (2019). BMJ Global Health 4:e001750.

The purpose of this study is to develop the Household Water Insecurity Experiences (HWISE) Scale to measure household water insecurity in an equivalent way across disparate cultural and ecological settings. The researchers implemented cross-sectional surveys in 8127 households across 28 sites in 23 low-income and middle-income countries. They collected data related to water insecurity in the prior month; sociodemographics; water acquisition, use, and storage; household food insecurity and perceived stress. The research team retained twelve items about experiences of household water insecurity for the HWISE Scale, and concluded that the scale will have the ability to quantify the prevalence, causes, and consequences of household water insecurity.

6. Tobacco smoking patterns in Samoa in 2010: Implications for interventions.

Adia, A.C., Hawley, N.L., Naseri, T., Reupena, M.S. & McGarvey, S.T. Tobacco Prevention and Cessation (in press).,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.

7. Changing body norms in the context of increasing body size: Samoa in 1995 and 2018.

To, S., Brewis, A.A., Pomer, A., Naseri, T., Reupena, M.S., McGarvey, S.T. & Hawley, N.L. American Journal of Human Biology (in press).

In this study, the researchers sought to understand how body size preferences changed in Samoa between 1995 and 2017–2019. They collected data from adults aged 31 to 59 years who had participated in two separate cross-sectional studies of obesity and cardiometabolic risk conducted in Samoa in the aforementioned years. Participants selected line drawings which represented their current size, their ideal size, the most attractive and healthiest size, and the lower/upper limits of “normal size.” The team found that in both sexes, body size preferences and perceived current average body size have increased, but that preference for bodies smaller than one’s own perceived current size have persisted. Additionally, the range of body sizes that participants considered “normal” has narrowed over time, suggesting decreased tolerance for extremes of body size. This study presents findings that may have implications for mental and physical health outcomes, inform the development of future health initiatives, and contribute to a better understanding of the relationship between body norms and weight-related public health efforts.

8. Associations between socioeconomic resources and adiposity traits in adults: evidence from Samoa.

Choy, C.C., Hawley, N.L., Naseri, T., Reupena, M.S. & McGarvey, S.T. Social Science and Medicine: Population Health (in press).

In this study, the researchers sought to understand the association of socioeconomic resources, assessed by household assets, with adult body mass index (BMI) and abdominal circumference (AC) in Samoa. The researchers used data from a genome-wide association study for obesity conducted in 2010, which included 3,370 Samoans between the ages of 24.5 and 65. They found that higher asset ownership was associated with higher BMI and AC, even after the relationship was controlled for potential confounders. Though there was significant economic growth in the years before the study was conducted, the obesity burden had not shifted to low socioeconomic groups, which was a trend observed in other countries further along in the economic transition. The researchers hypothesize that the relationship between socioeconomic resources and adiposity may be complicated in Samoa by migrant remittances received as both cash and household assets, and that social and physical environments may also constrain the positive health behavior change necessary to reduce obesity even in the context of high socioeconomic position. They suggest further investigation into the relationship between socioeconomic resources and adiposity, as well as these social and physical environments.

9. Exploring the paradoxical relationship of a CREBRF missense variant with body mass index and diabetes among Samoans: study protocol for the Soifua Manuia (‘Good Health’) observational cohort study.

Hawley. N.L., Pomer, A., Rivara, A.C., Rosenthal, S.L., Duckham R.L., Carlson, J.C., Naseri, T., Reupena, M.S., Selu, M., Lupematisilia, V., Unasa, F., Vesi, L., Fatu, T., Unasa, S., Faasalele-Savusa, K., Wetzel, A., Soti-Ulberg, C., Prescott, A., Siufaga, G., Penaia, C., To, S., LaMonica, L., Lameko, V., Choy, C.C., Crouter, S., Redline, S., Deka, R., Kershaw, E.E., Urban, Z., Minster, R.L., Weeks, D.E., McGarvey, S.T. JMIR Research Protocols (in press)

The purpose of the Soifua Manuia (‘Good Health’) study was to precisely characterize the association of the CREBRF genetic variant—rs373863828—with metabolic (body composition, glucose homeostasis) and behavioral traits (dietary intake, physical activity, sleep, weight control behaviors) that influence energy homeostasis. In 2010, a cohort of Samoan adults participated in a genome-wide association study (GWAS) of adiposity in Samoa. A follow-up, which was based on the absence of the CREBRF gene variant in participants, took place between August 2017 and March 2019. Over a period of 7-10 days, the research team collected anthropomorphic measurements; body composition assessments; point-of-care glycated hemoglobin measurements; fasting blood draw and oral glucose tolerance tests; urine collections; blood pressure, hand grip strength, objective physical activity and sleep apnea monitoring assessments; and questionnaire measures from each participant. In January 2019, a sub-sample of the study participants (n=118) also completed a buttock fat biopsy procedure for collection of subcutaneous adipose tissue samples. A total of 519 participants were enrolled as of March 2019, and data analyses are currently ongoing. According to the research team, this study will provide insights into how the genetic variant rs373863828, in CREBRF, functions on a whole-body level. These results could provide novel targets to prevent or treat obesity, diabetes, and associated metabolic disorders

10. Evolutionary genomics of Samoans.

Harris, D.N., Kessler, M.D., Shetty, A.C., Weeks, D.E., Minster, R.L., Browning, S., Cochrane, E.E., Deka, R., Hawley, N.L., Reupena, M.S., Naseri, T., Trans-Omics for Precision Medicine Consortium, TOPMed Population Genetics Working Group, McGarvey, S.T., O’Conner, T.D. Proceedings of the National Academy of Sciences (in press)
In this study, researchers used 1,197 Samoan high coverage genomes to identify populating splits between the major Samoan islands, and to detect asymmetrical gene flow to the capital city. Through this genome study, the researchers found that 25% of Samoan genomes come from Papuan-related ancestry, and believe this ancestry to be the source of the archaic Denisovan haplotypes in Samoans. Additionally, the data reveals that Samoans had an extreme bottleneck until approximately 1,000 years ago, which was followed by expansion between the islands, and then subsequent bottlenecks related to European colonization. According to the team, these results provide insight to the ongoing archaeological debate about the peopling of Samoa.

11. A missense variant in CREBRF is associated with taller stature in Samoans.

Carlson, J.C.*, Rosenthal, S.L.*, Russell, E.M., Hawley, N.L., Sun, G., Cheng, H., Naseri, T., Reupena, M.S., Deka, R., McGarvey, S.T., Weeks, D.E. & Minster, R.L. American Journal of Human Biology (in press)

The purpose of this study was to determine whether the minor allele of rs373863828, a missense variant in the CREBRF gene, was associated with height in a Samoam population. The researchers measured this association in two adult cohorts and in a separate cohort of children (age 5–18 years old) using linear mixed modeling. The team found evidence of a strong relationship between rs373863828 and a 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. These results suggest that the missense variant rs373863828 in the CREBRF gene, which was first identified through its association with larger BMI, may be related to an underlying biological mechanism affecting overall body size, including stature.