TY - JOUR AU - Kamble , Prasad G. AU - Gustafsson , Stefan AU - Pereira , Maria J. AU - Lundkvist , Per AU - Cook , Naomi AU - Lind , Lars AU - Franks , Paul W. AU - Fall , Tove AU - Eriksson , Jan W. AU - Ingelsson , Erik PY - 2018/01/05 Y2 - 2024/03/28 TI - Genotype-based recall to study metabolic effects of genetic variation: a pilot study of PPARG Pro12Ala carriers JF - Upsala Journal of Medical Sciences JA - ujms VL - 122 IS - 4 SE - Original Articles DO - 10.1080/03009734.2017.1405127 UR - https://ujms.net/index.php/ujms/article/view/6222 SP - 234–242 AB - 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. ER -