A thrifty variant in CREBRF strongly influences body mass index in Samoans

Minster, Ryan L.; Hawley, Nicola L.; Su, Chi-Ting; Sun, Guoqiang; Kershaw, Erin E.; Cheng, Hong; Buhule, Olive D.; Lin, Jerome; Reupena, Muagututi’a Sefuiva; Viali, Satupaitea; Tuitele, John; Naseri, Take; Urban, Zsolt; Deka, Ranjan; Weeks, Daniel E.; McGarvey, Stephen T.

doi:10.1038/ng.3620

Cited by 227 publications

(391 citation statements)

References 68 publications

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“…Over 80% of Samoans are overweight or obese [body mass index (BMI) > 26 kg/m 2 ], which is among the highest prevalence in the world (36). By genotyping ~3000 Samoans, a missense variant in CREBRF was found to be associated with BMI and fasting glucose levels.…”

Section: Impact Of Local Adaptation On Common Complex Diseasesmentioning

confidence: 99%

Going global by adapting local: A review of recent human adaptation

Fan

Hansen

et al. 2016

Science

275

224

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The spread of modern humans across the globe has led to genetic adaptations to diverse local environments. Recent developments in genomic technologies, statistical analyses, and expanded sampled populations have led to improved identification and fine-mapping of genetic variants associated with adaptations to regional living conditions and dietary practices. Ongoing efforts in sequencing genomes of indigenous populations, accompanied by the growing availability of “-omics” and ancient DNA data, promises a new era in our understanding of recent human evolution and the origins of variable traits and disease risks.

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Section: Impact Of Local Adaptation On Common Complex Diseasesmentioning

confidence: 99%

Going global by adapting local: A review of recent human adaptation

Fan

Hansen

et al. 2016

Science

275

224

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“…The high prevalence of cardiometabolic disorders among NHPI have been attributed to genetic/biological dispositions (Minster et al 2016), lifestyle behaviors (e.g., calorie-dense diet and physical inactivity) (Kolonel et al 2000), socioeconomic deprivation (e.g., lower income and education levels), sociocultural challenges (e.g., colonization and acculturation stressors) (Kaholokula, Nacapoy, and Dang 2009), psychosocial stressors (e.g., discrimination) (Kaholokula, Iwane, and Nacapoy 2010), environmental conditions (Mau et al 2008), and complex permutations of these variables (Kirtland, Cho, and Geiss 2015). Health interventions targeting cardiometabolic disorders in NHPI communities need to be culturally responsive and account for their interpersonal, sociocultural, and socioeconomic realities.…”

Section: Introductionmentioning

confidence: 99%

Culturally responsive approaches to health promotion for Native Hawaiians and Pacific Islanders

Kaholokula

Ing

Look

et al. 2018

Annals of Human Biology

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Context Obesity, diabetes, and cardiovascular disease (CVD) have reached epidemic proportions among Native Hawaiians/Pacific Islanders (NHPI). Culturally responsive interventions that account for their interpersonal, sociocultural, and socioeconomic realities is a public health priority. Objective To describe cultural adaptation and cultural grounded approaches to developing health interventions for NHPI and to review the culturally responsive approaches used by, and outcomes from, two long-standing community-based participatory research projects (CBPR) in Hawai‘i: PILI ‘Ohana and KāHOLO Projects. Methods A literature review of 14 studies from these two projects were done to exemplify the methods applied to culturally adapting existing evidence-based interventions and to developing novel interventions from the “ground up” to address health disparities in NHPI. Of the 14 studies reviewed, 11 were studies of the clinical and behavioral outcomes of both types of interventions. Results Both cultural adapted and cultural grounded approaches using community-based assets and NHPI cultural values/practices led to establishing sustainable and scalable interventions that significantly improved clinical measures of obesity, diabetes, and hypertension. Conclusion Several recommendations are provided based on the lessons learned from the PILI ‘Ohana and KāHOLO Projects. Multidisciplinary and transdisciplinary research using CBPR approaches are needed to elucidate how human biology is impacted by societal, environmental, and psychological factors that increase the risk for cardiometabolic diseases among NHPI to develop more effective health promotion interventions and public health policies.

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“…The gene seems to be linked at a cellular level to adipocyte responses to starvation, and the insertion of the mutation into adipocytes protects them from starvation-induced mortality. Whether this cell-based assay also means that the gene protects people from starvation-induced mortality is unclear, although this was the basis of the claim that the gene variant is 'thrifty' (Minster et al, 2016). If this is shown to be the case, it would be strong evidence that extremely rare 'thrifty genes' favouring survival in famines may exist and be selected for in small populations.…”

Section: Introductionmentioning

confidence: 99%

“…the shortfall between the known heritability and the proportion explained by common variants. One potential example of such a gene was found in the people living on the island of Samoa in the South Pacific Ocean (Minster et al, 2016). The variant is a mis-sense mutation that results in a coding change in the gene CREBRF.…”

Section: Introductionmentioning

confidence: 99%

The evolution of body fatness: trading off disease and predation risk

Speakman

2018

Journal of Experimental Biology

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Human obesity has a large genetic component, yet has many serious negative consequences. How this state of affairs has evolved has generated wide debate. The thrifty gene hypothesis was the first attempt to explain obesity as a consequence of adaptive responses to an ancient environment that in modern society become disadvantageous. The idea is that genes (or more precisely, alleles) predisposing to obesity may have been selected for by repeated exposure to famines. However, this idea has many flaws: for instance, selection of the supposed magnitude over the duration of human evolution would fix any thrifty alleles (famines kill the old and young, not the obese) and there is no evidence that hunter-gatherer populations become obese between famines. An alternative idea (called thrifty late) is that selection in famines has only happened since the agricultural revolution. However, this is inconsistent with the absence of strong signatures of selection at single nucleotide polymorphisms linked to obesity. In parallel to discussions about the origin of obesity, there has been much debate regarding the regulation of body weight. There are three basic models: the setpoint, settling point and dual-intervention point models. Selection might act against low and high levels of adiposity because food unpredictability and the risk of starvation selects against low adiposity whereas the risk of predation selects against high adiposity. Although evidence for the latter is quite strong, evidence for the former is relatively weak. The release from predation ∼2-million years ago is suggested to have led to the upper intervention point drifting in evolutionary time, leading to the modern distribution of obesity: the drifty gene hypothesis. Recent critiques of the dual-intervention point/ drifty gene idea are flawed and inconsistent with known aspects of energy balance physiology. Here, I present a new formulation of the dual-intervention point model. This model includes the novel suggestion that food unpredictability and starvation are insignificant factors driving fat storage, and that the main force driving up fat storage is the risk of disease and the need to survive periods of pathogen-induced anorexia. This model shows why two independent intervention points are more likely to evolve than a single set point. The molecular basis of the lower intervention point is likely based around the leptin pathway signalling. Determining the molecular basis of the upper intervention point is a crucial key target for future obesity research. A potential definitive test to separate the different models is also described.

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A thrifty variant in CREBRF strongly influences body mass index in Samoans

Cited by 227 publications

References 68 publications

Going global by adapting local: A review of recent human adaptation

Going global by adapting local: A review of recent human adaptation

Culturally responsive approaches to health promotion for Native Hawaiians and Pacific Islanders

The evolution of body fatness: trading off disease and predation risk

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