TY - JOUR
T1 - FGF21 signalling pathway and metabolic traits - genetic association analysis.
AU - Kaess, Bernhard M
AU - Barnes, Timothy A
AU - Stark, Klaus
AU - Charchar, Fadi J
AU - Waterworth, Dawn
AU - Song, Kijoung
AU - Wang, William Y S
AU - Vollenweider, Peter
AU - Waeber, Gerard
AU - Mooser, Vincent
AU - Zukowska-Szczechowska, Ewa
AU - Samani, Nilesh J
AU - Hengstenberg, Christian
AU - Tomaszewski, Maciej
N1 - (PG/06/097, British Heart Foundation, United KingdomR03 TW007165, FIC NIH HHS, United StatesR03 TW007165, FIC NIH HHS, United StatesR03 TW007165-03, FIC NIH HHS, United States
PY - 2010/12
Y1 - 2010/12
N2 - Fibroblast growth factor 21 (FGF21) is a novel master regulator of metabolic profile. The biological actions of FGF21 are elicited upon its klotho beta (KLB)-facilitated binding to FGF receptor 1 (FGFR1), FGFR2 and FGFR3. We hypothesised that common polymorphisms in the FGF21 signalling pathway may be associated with metabolic risk. At the screening stage, we examined associations between 63 common single-nucleotide polymorphisms (SNPs) in five genes of this pathway (FGF21, KLB, FGFR1, FGFR2, FGFR3) and four metabolic phenotypes (LDL cholesterol - LDL-C, HDL-cholesterol - HDL-C, triglycerides and body mass index) in 629 individuals from Silesian Hypertension Study (SHS). Replication analyses were performed in 5478 unrelated individuals of the Swiss CoLaus cohort (imputed genotypes) and in 3030 directly genotyped individuals of the German Myocardial Infarction Family Study (GerMIFS). Of 54 SNPs that met quality control criteria after genotyping in SHS, 4 (rs4733946 and rs7012413 in FGFR1; rs2071616 in FGFR2 and rs7670903 in KLB) showed suggestive association with LDL-C (P=0.0006, P=0.0013, P=0.0055, P=0.011, respectively) and 1 (rs2608819 in KLB) was associated with body mass index (P=0.011); all with false discovery rate q
AB - Fibroblast growth factor 21 (FGF21) is a novel master regulator of metabolic profile. The biological actions of FGF21 are elicited upon its klotho beta (KLB)-facilitated binding to FGF receptor 1 (FGFR1), FGFR2 and FGFR3. We hypothesised that common polymorphisms in the FGF21 signalling pathway may be associated with metabolic risk. At the screening stage, we examined associations between 63 common single-nucleotide polymorphisms (SNPs) in five genes of this pathway (FGF21, KLB, FGFR1, FGFR2, FGFR3) and four metabolic phenotypes (LDL cholesterol - LDL-C, HDL-cholesterol - HDL-C, triglycerides and body mass index) in 629 individuals from Silesian Hypertension Study (SHS). Replication analyses were performed in 5478 unrelated individuals of the Swiss CoLaus cohort (imputed genotypes) and in 3030 directly genotyped individuals of the German Myocardial Infarction Family Study (GerMIFS). Of 54 SNPs that met quality control criteria after genotyping in SHS, 4 (rs4733946 and rs7012413 in FGFR1; rs2071616 in FGFR2 and rs7670903 in KLB) showed suggestive association with LDL-C (P=0.0006, P=0.0013, P=0.0055, P=0.011, respectively) and 1 (rs2608819 in KLB) was associated with body mass index (P=0.011); all with false discovery rate q
U2 - 10.1038/ejhg.2010.130
DO - 10.1038/ejhg.2010.130
M3 - Article
C2 - 20717167
SN - 1476-5438
VL - 18
JO - European journal of human genetics : EJHG
JF - European journal of human genetics : EJHG
IS - 12
ER -