Association of variants in the PCSK1 gene with obesity in the EPIC-Norfolk study

TY - JOUR

T1 - Association of variants in the PCSK1 gene with obesity in the EPIC-Norfolk study

AU - Oskari Kilpeläinen, Tuomas

AU - Bingham, Sheila A

AU - Khaw, Kay-Tee

AU - Wareham, Nicholas J

AU - Loos, Ruth J F

PY - 2009/9/15

Y1 - 2009/9/15

N2 - Recently, the rs6232 (N221D) and rs6235 (S690T) SNPs in the PCSK1 gene were associated with obesity in a meta-analysis comprising more than 13 000 individuals of European ancestry. Each additional minor allele of rs6232 or rs6235 was associated with a 1.34- or 1.22-fold increase in the risk of obesity, respectively. So far, only one relatively small study has aimed to replicate these findings, but could not confirm the association of the rs6235 SNP and did not study the rs6232 variant. In the present study, we examined the associations of the rs6232 and rs6235 SNPs with obesity in a population-based cohort consisting of 20 249 individuals of European descent from Norfolk, UK. Logistic regression and generalized linear models were used to test the associations of the risk alleles with obesity and related quantitative traits, respectively. Neither of the SNPs was significantly associated with obesity, BMI or waist circumference under the additive genetic model (P > 0.05). However, we observed an interaction between rs6232 and age on the level of BMI (P = 0.010) and risk of obesity (P = 0.020). The rs6232 SNP was associated with BMI (P = 0.021) and obesity (P = 0.022) in the younger individuals [less than median age (59 years)], but not among the older age group (P = 0.81 and P = 0.68 for BMI and obesity, respectively). In conclusion, our data suggest that the PCSK1 rs6232 and rs6235 SNPs are not major contributors to common obesity in the general population. However, the effect of rs6232 may be age-dependent.

AB - Recently, the rs6232 (N221D) and rs6235 (S690T) SNPs in the PCSK1 gene were associated with obesity in a meta-analysis comprising more than 13 000 individuals of European ancestry. Each additional minor allele of rs6232 or rs6235 was associated with a 1.34- or 1.22-fold increase in the risk of obesity, respectively. So far, only one relatively small study has aimed to replicate these findings, but could not confirm the association of the rs6235 SNP and did not study the rs6232 variant. In the present study, we examined the associations of the rs6232 and rs6235 SNPs with obesity in a population-based cohort consisting of 20 249 individuals of European descent from Norfolk, UK. Logistic regression and generalized linear models were used to test the associations of the risk alleles with obesity and related quantitative traits, respectively. Neither of the SNPs was significantly associated with obesity, BMI or waist circumference under the additive genetic model (P > 0.05). However, we observed an interaction between rs6232 and age on the level of BMI (P = 0.010) and risk of obesity (P = 0.020). The rs6232 SNP was associated with BMI (P = 0.021) and obesity (P = 0.022) in the younger individuals [less than median age (59 years)], but not among the older age group (P = 0.81 and P = 0.68 for BMI and obesity, respectively). In conclusion, our data suggest that the PCSK1 rs6232 and rs6235 SNPs are not major contributors to common obesity in the general population. However, the effect of rs6232 may be age-dependent.

KW - Adult

KW - Age Factors

KW - Aged

KW - Female

KW - Great Britain

KW - Humans

KW - Male

KW - Middle Aged

KW - Neuropeptides

KW - Obesity

KW - Polymorphism, Single Nucleotide

U2 - 10.1093/hmg/ddp280

DO - 10.1093/hmg/ddp280

M3 - Journal article

C2 - 19528091

SN - 0964-6906

VL - 18

SP - 3496

EP - 3501

JO - Human Molecular Genetics

JF - Human Molecular Genetics

IS - 18

ER -