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The Association of Common Variants in PCSK1 With Obesity: A HuGE Review and Meta-Analysis

Stijnen, Pieter; Tuand, Krizia; Varga, Tibor V.; Franks, Paul LU ; Aertgeerts, Bert and Creemers, John W. M. (2014) In American Journal of Epidemiology 180(11). p.1051-1065
Abstract
Congenital deficiency of the proprotein convertase subtilisine/kexin type 1 gene (PCSK1), which encodes proprotein convertase 1/3, causes a severe multihormonal disorder marked by early-onset obesity. The single nucleotide polymorphisms (SNPs) rs6232 and rs6234-rs6235 in PCSK1 have been associated with obesity. However, case-control studies carried out in populations of different ethnicities have only partly replicated this association. Moreover, these SNPs have only weakly been associated with body mass index (weight (kg)/height (m)(2)) at a genome-wide level of significance. To investigate this discrepancy, we conducted a systematic search for studies published before December 2013 and extracted relevant data. Pooled estimates were... (More)
Congenital deficiency of the proprotein convertase subtilisine/kexin type 1 gene (PCSK1), which encodes proprotein convertase 1/3, causes a severe multihormonal disorder marked by early-onset obesity. The single nucleotide polymorphisms (SNPs) rs6232 and rs6234-rs6235 in PCSK1 have been associated with obesity. However, case-control studies carried out in populations of different ethnicities have only partly replicated this association. Moreover, these SNPs have only weakly been associated with body mass index (weight (kg)/height (m)(2)) at a genome-wide level of significance. To investigate this discrepancy, we conducted a systematic search for studies published before December 2013 and extracted relevant data. Pooled estimates were calculated for overall and subgroup analyses. This meta-analysis confirmed the association of PCSK1 SNPs with obesity and provides the first evidence that the association between PCSK1 rs6232 and obesity is stronger for childhood obesity than for adult obesity. Moreover, we identified weak associations with body mass index and significantly stronger associations with waist circumference for rs6234-rs6235. No difference was found in the association with different obesity grades, and no association of PCSK1 rs6234-rs6235 with obesity was identified in Asian populations. This systematic Human Genome Epidemiology (HuGE) review showed convincingly that the SNPs rs6232, rs6234, and rs6235 in PCSK1 are associated with obesity in Caucasians. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
proprotein convertase 1/3, waist, circumference, PCSK1, obesity, human, genome, genetic epidemiology, body mass index, genetic association studies
in
American Journal of Epidemiology
volume
180
issue
11
pages
1051 - 1065
publisher
Oxford University Press
external identifiers
  • wos:000345780800001
  • scopus:84925222316
ISSN
0002-9262
DOI
10.1093/aje/kwu237
language
English
LU publication?
yes
id
7e138054-883c-4f95-8e23-9f3dcc82980a (old id 4962611)
date added to LUP
2015-02-03 07:04:18
date last changed
2017-03-19 03:01:26
@article{7e138054-883c-4f95-8e23-9f3dcc82980a,
  abstract     = {Congenital deficiency of the proprotein convertase subtilisine/kexin type 1 gene (PCSK1), which encodes proprotein convertase 1/3, causes a severe multihormonal disorder marked by early-onset obesity. The single nucleotide polymorphisms (SNPs) rs6232 and rs6234-rs6235 in PCSK1 have been associated with obesity. However, case-control studies carried out in populations of different ethnicities have only partly replicated this association. Moreover, these SNPs have only weakly been associated with body mass index (weight (kg)/height (m)(2)) at a genome-wide level of significance. To investigate this discrepancy, we conducted a systematic search for studies published before December 2013 and extracted relevant data. Pooled estimates were calculated for overall and subgroup analyses. This meta-analysis confirmed the association of PCSK1 SNPs with obesity and provides the first evidence that the association between PCSK1 rs6232 and obesity is stronger for childhood obesity than for adult obesity. Moreover, we identified weak associations with body mass index and significantly stronger associations with waist circumference for rs6234-rs6235. No difference was found in the association with different obesity grades, and no association of PCSK1 rs6234-rs6235 with obesity was identified in Asian populations. This systematic Human Genome Epidemiology (HuGE) review showed convincingly that the SNPs rs6232, rs6234, and rs6235 in PCSK1 are associated with obesity in Caucasians.},
  author       = {Stijnen, Pieter and Tuand, Krizia and Varga, Tibor V. and Franks, Paul and Aertgeerts, Bert and Creemers, John W. M.},
  issn         = {0002-9262},
  keyword      = {proprotein convertase 1/3,waist,circumference,PCSK1,obesity,human,genome,genetic epidemiology,body mass index,genetic association studies},
  language     = {eng},
  number       = {11},
  pages        = {1051--1065},
  publisher    = {Oxford University Press},
  series       = {American Journal of Epidemiology},
  title        = {The Association of Common Variants in PCSK1 With Obesity: A HuGE Review and Meta-Analysis},
  url          = {http://dx.doi.org/10.1093/aje/kwu237},
  volume       = {180},
  year         = {2014},
}