A positively selected FBN1 missense variant reduces height in Peruvian individuals

Asgari, Samira; Luo, Yang; Akbari, Ali; Belbin, Gillian M.; Li, Xinyi; Harris, Daniel N.; Selig, Martin K.; Bartell, Eric; Calderón, Róger; Slowikowski, Kamil; Contreras, Carmen; Yataco, Rosa; Galea, Jerome T; Jiménez, Judith; Coit, Julia; Farroñay, Chandel; Nazarian, Rosalynn M.; O’Connor, Timothy D.; Dietz, Harry C.; Hirschhorn, Joel N.; Guio, Heinner; Lecca, Leonid; Kenny, Eimear E.; Freeman, Esther E.; Murray, Megan; Raychaudhuri, Soumya

doi:10.1038/s41586-020-2302-0

Cited by 46 publications

(52 citation statements)

References 68 publications

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“…Previous GWAS probably missed this variant due to its low frequency in European populations (0.017 compared with 0.98 in the Inuit); nevertheless, it has a much greater effect on height than other variants previously identified through GWAS 170 . Similarly, a recent study of height in 3,000 Peruvians identified another variant with an even greater influence on height 171 . The growth of large DNA biobanks in which hundreds of thousands of patients’ EHRs are linked to DNA samples represents a substantial untapped resource for evolutionary medicine 5 , 86 , 87 .…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 78%

The influence of evolutionary history on human health and disease

et al. 2021

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Section: Conclusion and Future Perspectivesmentioning

confidence: 78%

The influence of evolutionary history on human health and disease

et al. 2021

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“…In this regard, the WHtR, by incorporating the patient's height in the formula, overcomes the limitation of assuming the same cut-off point for individuals with different heights and body proportions (23,51) . This fact is important in the Peruvian context since a large proportion of the population of this country have a low height, and a measurement taking into account this characteristic would give a better estimation of risk (25) . In addition, an inverse association of height with morbidity and mortality due to CVD has been described (50) , which could be explained by adult height reflecting the nutritional situation in early childhood.…”

Section: Discussionmentioning

confidence: 99%

“…This is very important in the Peruvian population because it has one of the lower heights worldwide (24) . Furthermore, a genetic variation has even been postulated in a recently published study that would explain the short stature on this population (25) . The presence of this genetic variation would produce a reduction of 2•2 to 4•4 cm in height and is more frequent in the population from the coast -one of the three natural regions of Peru which comprises 55•9 % of the total population -than in the highlands or the Jungle.…”

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confidence: 88%

Cut-off points of anthropometric markers associated with hypertension and diabetes in Peru: Demographic and Health Survey 2018

Hernández-Vasquéz

Azañedo

Vargas-Fernández

et al. 2020

Public Health Nutr.

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Objectives To determine the optimal anthropometric cut-off points for predicting the likelihood ratios of hypertension and diabetes in the Peruvian population. Design A cross-sectional study was performed to establish cut-off values for body mass index (BMI) and waist circumference [WC], waist-height ratio [WHtR], and Conicity index [C-index]) associated with increased risk of hypertension and diabetes. Youden’s index (YIndex), area under the curve (AUC), sensitivity and specificity were considered. Settings Peruvian households. Participants Peruvian population over the age of 18 years. Results 31,553 subjects were included; 57% being women. Among the women, 53.06% belonged to the 25 to 44-year-old age group [mean age: 41.66 in men and 40.02 in women]. The mean BMI, WHtR and C-index values were higher in women 27.49, 0.61, 1.30 respectively; while the mean WC value was higher in men 92.12 cm (SD±11.28). The best predictors of hypertension in men were the WHtR (AUC=0.64) and the C-index (AUC=0.64) with an optimal cut-off point of 0.57 (YIndex=0.284) and 1.301 (YIndex=0.284), respectively. Women showed an AUC of 0.63 and 0.61 in the WHtR and C-index, respectively, with an optimal cut-off of 0.61 (YIndex=0.236) and 1.323 (YIndex=0.225). The best predictor for diabetes was the C-index: with an AUC=0.67 and an optimal cut-off of 1.337 (YIndex=0.346) for men, and an AUC=0.66 and optimal cut-off of 1.313 (YIndex=0.319) for women. Conclusions Our findings show that in Peruvian adults, the WHtR and the C-index have the strongest association with hypertension in both sexes. Likewise, the C-index had the strongest association with diabetes.

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“…A central goal of research in evolutionary genetics is to understand how new traits are built. Much of the literature to date has focused on putatively adaptive trait variation within a species, in the wild (Asgari et al, 2020;Chan et al, 2010;Cleves et al, 2014;Field et al, 2016;Linnen et al, 2013;Will et al, 2010) and in the lab (Blount et al, 2012;Castro et al, 2019;Good et al, 2017;Tenaillon et al, 2016). These systems have enabled studies of the mechanisms of adaptation over relatively short timescales.…”

Section: Introductionmentioning

confidence: 99%

“…A central goal of research in evolutionary genetics is to understand how new traits are built. Much of the literature to date focuses on adaptive trait innovation within a species, in the wild (Asgari et al, 2020; Chan et al, 2010; Cleves et al, 2014; Field et al, 2016; Linnen et al, 2013; Will et al, 2010) and in the lab (Blount et al, 2012; Castro et al, 2019; Good et al, 2017; Tenaillon et al, 2016). These systems have enabled studies of short-term adaptation, its genetics (Barroso-Batista et al, 2014; Castro et al, 2019; Garud et al, 2015; Good et al, 2017; Harris et al, 2018; Xie et al, 2019) and its dynamics (Blount et al, 2012; Toprak et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Population and comparative genetics of thermotolerance divergence between yeast species

Abrams

Dubin

AlZaben

et al. 2020

Preprint

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Many familiar traits in the natural world—from lions’ manes to the longevity of bristlecone pine trees—arose in the distant past, and have long since fixed in their respective species. A key challenge in evolutionary genetics is to figure out how and why species-defining traits have come to be. We used the growth advantage of the yeast Saccharomyces cerevisiae at high temperature, relative to its sister species Saccharomyces paradoxus, as a model for addressing these questions. Starting with a suite of identified loci where the S. cerevisiae allele promotes thermotolerance, we detected robust signatures of positive selection with sequence-based molecular evolution tests. These included recurrent signal across dozens of S. cerevisiae populations; we thus propose an approximate date for a selective sweep of thermotolerance alleles in the ancestor of the modern lineages of the species. In focused experiments on the chromosome segregation gene ESP1, a particularly strong contributor to thermotolerance, the S. paradoxus allele conferred a defect in cell division at high temperature, relative to the S. cerevisiae allele. Only divergent sites in the ESP1 coding region mattered phenotypically, with no functional impact detectable from the promoter. This study of an adaptation that likely arose long ago, by sweeps at many unlinked loci, sets the groundwork for evolutionary genetics in ancient traits across Eukarya.

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A positively selected FBN1 missense variant reduces height in Peruvian individuals

Cited by 46 publications

References 68 publications

The influence of evolutionary history on human health and disease

The influence of evolutionary history on human health and disease

Cut-off points of anthropometric markers associated with hypertension and diabetes in Peru: Demographic and Health Survey 2018

Population and comparative genetics of thermotolerance divergence between yeast species

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