title: A GWAS follow-up of obesity-related SNPs in SYPL2 reveals sex-specific association with hip circumference.
abstract: A novel single-nucleotide polymorphism (SNP) associated with morbid obesity was recently identified by exome sequencing. The purpose of this study was to follow up this low-frequency coding SNP located within theSYPL2locus and associated with body mass index in order to reveal novel associations with obesity-related traits.
  
  
  
  The body mass index-associated SNP (rs62623713 A>G [chr1:109476817/hg19]) and two tagging SNPs within theSYPL2locus, rs9661614 T>C (chr1:109479215) and rs485660 G>A (chr1:109480810), were genotyped in the obesity (n= 3,017) and the infogene (n= 676) cohorts, which were further combined, leading to a larger cohort of 3,693 individuals. Association testing was performed by general linear models in the obesity cohort and validated by joint analysis in the combined cohort.
  
  
  
  rs9661614 and rs485660 were significantly associated with hip circumference (HC) in the obesity cohort, with heterozygotes exhibiting a significantly lower HC. These results were validated by joint analysis for rs9661614 (false discovery rate [FDR]-correctedP= 7.5 × 10-4) and, to a lesser extent, for rs485660 (FDR correctedP= 3.9 × 10-2). The association with HC remained significant for rs9661614 when tested independently in women (FDR-correctedP= 1.7 × 10-2), but not for rs485660 (FDR-correctedP= 0.2). Both associations were absent in men.
  
  
  
  This study reveals strong evidence for a novel association between rs9661614 (T>C) and HC in women, which likely reflects a preferential association ofSYPL2to a gynoid profile of fat distribution. The study findings support a clinical significance ofSYPL2worth considering when assessing risk factors associated with obesity.
authors.affiliation: Institute of Nutrition and Functional Foods (INAF) Laval University Quebec Quebec Canada; School of Nutrition Laval University Quebec Quebec Canada.
authors.forename: J
authors.initials: J
authors.lastname: de Toro-Martín
authors.affiliation: Institute of Nutrition and Functional Foods (INAF) Laval University Quebec Quebec Canada; School of Nutrition Laval University Quebec Quebec Canada.
authors.forename: F
authors.initials: F
authors.lastname: Guénard
authors.affiliation: School of Nutrition Laval University Quebec Quebec Canada; Quebec Heart and Lung Institute Research Center Quebec Quebec Canada.
authors.forename: A
authors.initials: A
authors.lastname: Tchernof
authors.affiliation: Quebec Heart and Lung Institute Research Center Quebec Quebec Canada; Department of Medicine Laval University Quebec Quebec Canada.
authors.forename: Y
authors.initials: Y
authors.lastname: Deshaies
authors.affiliation: Institute of Nutrition and Functional Foods (INAF) Laval University Quebec Quebec Canada; Department of Kinesiology Laval University Quebec Quebec Canada.
authors.forename: L
authors.initials: L
authors.lastname: Pérusse
authors.affiliation: Department of Surgery Laval University Quebec Quebec Canada.
authors.forename: S
authors.initials: S
authors.lastname: Biron
authors.affiliation: Department of Surgery Laval University Quebec Quebec Canada.
authors.forename: O
authors.initials: O
authors.lastname: Lescelleur
authors.affiliation: Department of Surgery Laval University Quebec Quebec Canada.
authors.forename: L
authors.initials: L
authors.lastname: Biertho
authors.affiliation: Department of Surgery Laval University Quebec Quebec Canada.
authors.forename: S
authors.initials: S
authors.lastname: Marceau
authors.affiliation: Institute of Nutrition and Functional Foods (INAF) Laval University Quebec Quebec Canada; School of Nutrition Laval University Quebec Quebec Canada.
authors.forename: M-C
authors.identifier: 0000-0002-7017-5848
authors.initials: MC
authors.lastname: Vohl
keywords: Hip circumference; SYPL2; obesity; replication study