ArticlePloS one2015
Signatures of natural selection at the FTO (fat mass and obesity associated) locus in human populations.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
5 citing papers in PubMed, 12 citations in OpenAlex.
- Common BMI and diabetes-related genetic variants: A pilot study among indigenous people in the Brazilian Amazon.Genetics and molecular biology · 2022Article
- Genetics of Obesity in East Asians.Frontiers in genetics · 2020Review
- FTO haplotyping underlines high obesity risk for European populations.BMC medical genomics · 2019Article
- Medical genomics research at BGRS-2018.BMC medical genomics · 2019Article
- Polymorphisms of the FTO and MTHFR genes and vascular, inflammatory and metabolic marker levels in postmenopausal women.Journal of endocrinological investigation · 2016Article
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
aimsPolymorphisms in the first intron of FTO have been robustly replicated for associations with obesity. In the Sorbs, a Slavic population resident in Germany, the strongest effect on body mass index (BMI) was found for a variant in the third intron of FTO (rs17818902). Since this may indicate population specific effects of FTO variants, we initiated studies testing FTO for signatures of selection in vertebrate species and human populations.
methodsFirst, we analyzed the coding region of 35 vertebrate FTO orthologs with Phylogenetic Analysis by Maximum Likelihood (PAML, ω = dN/dS) to screen for signatures of selection among species. Second, we investigated human population (Europeans/CEU, Yoruba/YRI, Chinese/CHB, Japanese/JPT, Sorbs) SNP data for footprints of selection using DnaSP version 4.5 and the Haplotter/PhaseII. Finally, using ConSite we compared transcription factor (TF) binding sites at sequences harbouring FTO SNPs in intron three.
resultsPAML analyses revealed strong conservation in coding region of FTO (ω<1). Sliding-window results from population genetic analyses provided highly significant (p<0.001) signatures for balancing selection specifically in the third intron (e.g. Tajima's D in Sorbs = 2.77). We observed several alterations in TF binding sites, e.g. TCF3 binding site introduced by the rs17818902 minor allele.
conclusionPopulation genetic analysis revealed signatures of balancing selection at the FTO locus with a prominent signal in intron three, a genomic region with strong association with BMI in the Sorbs. Our data support the hypothesis that genes associated with obesity may have been under evolutionary selective pressure.
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