FTO haplotyping underlines high obesity risk for European populations
| Autor: | Arcady L. Markel, Vladimir N. Babenko, Junaid Gamieldien, Roman O. Babenko |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
lcsh:Internal medicine lcsh:QH426-470 Population genetics Alpha-Ketoglutarate-Dependent Dioxygenase FTO Single-nucleotide polymorphism Locus (genetics) Genome-wide association study Biology Polymorphism Single Nucleotide FTO gene White People 03 medical and health sciences 0302 clinical medicine Gene Frequency Risk Factors Genetics Humans Obesity Allele lcsh:RC31-1245 Allele frequency Alleles Genetics (clinical) Principal Component Analysis Research Genomics Introns Minor allele frequency lcsh:Genetics Genetics Population 030104 developmental biology Haplotypes 030220 oncology & carcinogenesis Genome-Wide Association Study |
| Zdroj: | BMC Medical Genomics, Vol 12, Iss S2, Pp 107-115 (2019) BMC Medical Genomics |
| ISSN: | 1755-8794 |
| Popis: | Background Fat mass and obesity-associated (FTO) gene has been under close investigation since the discovery of its high impact on the obesity status in 2007 by a range of publications. Recent report on its implication in adipocytes underscored its molecular and functional mechanics in pathology. Still, the population specific features of the locus structure have not been approached in detail. Methods We analyzed the population specific haplotype profiles of FTO genomic locus identified by Genome Wide Association Studies (GWAS) for the high obesity risk by examining eighteen 1000G populations from 4 continental groups. The GWAS SNPs cluster is located in the FTO gene intron 1 spanning around 70 kb. Results We reconstructed the ancestral state of the locus, which comprised low-risk major allele found in all populations, and two minor risk-associated alleles, each one specific for African and European populations, correspondingly. The locus structure and its allele frequency distribution underscore the high risk allele frequency specifically for the European population. South Asian populations have the second highest frequency of risk alleles, while East Asian populations have the lowest. African population-specific minor allele was only partially risk-associated. All of the GWAS SNPs considered are manifested by low risk alleles as reference (major) ones (p > 0.5) in each of the continental groups. Strikingly, rs1421085, recently reported as a causal SNP, was found to be monomorphic in ancestral (African) populations, implying possible selection sweep in the course of its rapid fixation, as reported previously. Conclusion The observations underscore varying FTO -linked risk in the manifestation of population specific epidemiology of genetically bound obesity. The results imply that the FTO locus is one of the major genetic determinants for obesity risk from GWAS SNPs set. Electronic supplementary material The online version of this article (10.1186/s12920-019-0491-x) contains supplementary material, which is available to authorized users. |
| Databáze: | OpenAIRE |
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