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

Author:
  • Pieter Stijnen
  • Krizia Tuand
  • Tibor V. Varga
  • Paul Franks
  • Bert Aertgeerts
  • John W. M. Creemers
Publishing year: 2014
Language: English
Pages: 1051-1065
Publication/Series: American Journal of Epidemiology
Volume: 180
Issue: 11
Document type: Journal article review
Publisher: Oxford University Press

Abstract english

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.

Keywords

  • Public Health, Global Health, Social Medicine and Epidemiology
  • proprotein convertase 1/3
  • waist
  • circumference
  • PCSK1
  • obesity
  • human
  • genome
  • genetic epidemiology
  • body mass index
  • genetic association studies

Other

Published
  • Genetic and Molecular Epidemiology
  • ISSN: 0002-9262
Paul Franks
E-mail: paul.franks [at] med.lu.se

Principal investigator

Genetic and Molecular Epidemiology

+46 40 39 11 49

60-12-021

33

Lund University Diabetes Centre, CRC, SUS Malmö, Entrance 72, House 91:12. SE-205 02 Malmö. Telephone: +46 40 39 10 00