Genotype-based recall to study metabolic effects of genetic variation: a pilot study ofPPARGPro12Ala carriers
| العنوان: | Genotype-based recall to study metabolic effects of genetic variation: a pilot study ofPPARGPro12Ala carriers |
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| المؤلفون: | Per Lundkvist, Maria J. Pereira, Lars Lind, Paul W. Franks, Jan W. Eriksson, Prasad G. Kamble, Tove Fall, Erik Ingelsson, Stefan Gustafsson, Naomi L. Cook |
| المصدر: | Upsala Journal of Medical Sciences, Vol 122, Iss 4, Pp 234-242 (2017) Upsala Journal of Medical Sciences |
| بيانات النشر: | Uppsala Medical Society, 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, Heterozygote, medicine.medical_specialty, Genotype, lcsh:Medicine, Pilot Projects, Type 2 diabetes, Endocrinology and Diabetes, PPARG Pro12Ala, 03 medical and health sciences, Genetic variation, medicine, Humans, Missense mutation, Aged, Medicinsk genetik, Genetics, business.industry, lcsh:R, Original Articles, General Medicine, Middle Aged, Anthropometry, medicine.disease, PPAR gamma, Minor allele frequency, Phenotype, 030104 developmental biology, Endokrinologi och diabetes, Cohort, Genotype-based recall, Medical genetics, Female, business, metabolism, Medical Genetics, Genome-Wide Association Study |
| الوصف: | Aim: To assess practical implications of genotype-based recall (GBR) studies, an increasingly popular approach for in-depth characterization of genotype–phenotype relationships. Methods: We genotyped 2500 participants from the Swedish EpiHealth cohort and considered loss-of-function and missense variants in genes with relation to cardiometabolic traits as the basis for our GBR study. Therefore, we focused on carriers and non-carriers of the PPARG Pro12Ala (rs1801282) variant, as it is a relatively common variant with a minor allele frequency (MAF) of 0.14. It has also been shown to affect ligand binding and transcription, and carriage of the minor allele (Ala12) is associated with a reduced risk of type 2 diabetes. We re-invited 39 Pro12Pro, 34 Pro12Ala, and 30 Ala12Ala carriers and performed detailed anthropometric and serological assessments. Results: The participation rates in the GBR study were 31%, 44%, and 40%, and accordingly we included 12, 15, and 13 individuals with Pro12Pro, Pro12Ala, and Ala12Ala variants, respectively. There were no differences in anthropometric or metabolic variables among the different genotype groups. Conclusions: Our report highlights that from a practical perspective, GBR can be used to study genotype–phenotype relationships. This approach can prove to be a valuable tool for follow-up findings from large-scale genetic discovery studies by undertaking detailed phenotyping procedures that might not be feasible in large studies. However, our study also illustrates the need for a larger pool of genotyped or sequenced individuals to allow for selection of rare variants with larger effects that can be examined in a GBR study of the present size. |
| وصف الملف: | application/pdf |
| تدمد: | 2000-1967 0300-9734 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::91a97921f3614ce8bb7bb2479ee191a9Test https://doi.org/10.1080/03009734.2017.1405127Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....91a97921f3614ce8bb7bb2479ee191a9 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20001967 03009734 |
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