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Genotype-based recall to study metabolic effects of genetic variation : a pilot study of PPARG Pro12Ala carriers

Kamble, Prasad G.; Gustafsson, Stefan LU ; Pereira, Maria J.; Lundkvist, Per; Cook, Naomi; Lind, Lars; Franks, Paul W. LU ; Fall, Tove LU ; Eriksson, Jan W. and Ingelsson, Erik (2017) In Upsala Journal of Medical Sciences 122(4). p.234-242
Abstract

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... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Genotype-based recall, metabolism, PPARG Pro12Ala
in
Upsala Journal of Medical Sciences
volume
122
issue
4
pages
9 pages
publisher
Taylor & Francis
external identifiers
  • scopus:85041207146
ISSN
0300-9734
DOI
10.1080/03009734.2017.1405127
language
English
LU publication?
yes
id
295bc90f-0dbe-453d-a392-03042308032b
date added to LUP
2018-02-23 12:14:49
date last changed
2018-02-24 03:00:02
@article{295bc90f-0dbe-453d-a392-03042308032b,
  abstract     = {<p>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.</p>},
  author       = {Kamble, Prasad G. and Gustafsson, Stefan and Pereira, Maria J. and Lundkvist, Per and Cook, Naomi and Lind, Lars and Franks, Paul W. and Fall, Tove and Eriksson, Jan W. and Ingelsson, Erik},
  issn         = {0300-9734},
  keyword      = {Genotype-based recall,metabolism,PPARG Pro12Ala},
  language     = {eng},
  month        = {10},
  number       = {4},
  pages        = {234--242},
  publisher    = {Taylor & Francis},
  series       = {Upsala Journal of Medical Sciences},
  title        = {Genotype-based recall to study metabolic effects of genetic variation : a pilot study of PPARG Pro12Ala carriers},
  url          = {http://dx.doi.org/10.1080/03009734.2017.1405127},
  volume       = {122},
  year         = {2017},
}