TY - JOUR
T1 - Contribution of common non-synonymous variants in PCSK1 to body mass index variation and risk of obesity: a systematic review and meta-analysis with evidence from up to 331 175 individuals.
JF - Human Molecular Genetics
Y1 - 2015
A1 - Nead, Kevin T
A1 - Li, Aihua
A1 - Wehner, Mackenzie R
A1 - Neupane, Binod
A1 - Gustafsson, Stefan
A1 - Adam S Butterworth
A1 - Engert, James C
A1 - Davis, A Darlene
A1 - Hegele, Robert A
A1 - Miller, Ruby
A1 - den Hoed, Marcel
A1 - Khaw, Kay-Tee
A1 - Kilpeläinen, Tuomas O
A1 - Wareham, Nick
A1 - Edwards, Todd L
A1 - Hallmans, Göran
A1 - Varga, Tibor V
A1 - Sharon L R Kardia
A1 - Smith, Jennifer A
A1 - Zhao, Wei
A1 - Jessica Faul
A1 - David R Weir
A1 - Mi, Jie
A1 - Xi, Bo
A1 - Quinteros, Samuel Canizales
A1 - Cooper, Cyrus
A1 - Sayer, Avan Aihie
A1 - Jameson, Karen
A1 - Grøntved, Anders
A1 - Myriam Fornage
A1 - Stephen Sidney
A1 - Hanis, Craig L
A1 - Highland, Heather M
A1 - Häring, Hans-Ulrich
A1 - Heni, Martin
A1 - Lasky-Su, Jessica
A1 - Weiss, Scott T
A1 - Gerhard, Glenn S
A1 - Still, Christopher
A1 - Melka, Melkaey M
A1 - Pausova, Zdenka
A1 - Paus, Tomáš
A1 - Grant, Struan F A
A1 - Hakonarson, Hakon
A1 - Price, R Arlen
A1 - Wang, Kai
A1 - Scherag, Andre
A1 - Hebebrand, Johannes
A1 - Hinney, Anke
A1 - Franks, Paul W
A1 - Timothy M Frayling
A1 - McCarthy, Mark I
A1 - Hirschhorn, Joel N
A1 - Ruth J F Loos
A1 - Ingelsson, Erik
A1 - Gerstein, Hertzel C
A1 - Yusuf, Salim
A1 - Beyene, Joseph
A1 - Anand, Sonia S
A1 - Meyre, David
KW - Alleles
KW - Body Mass Index
KW - Genetic Predisposition to Disease
KW - Genetic Variation
KW - Humans
KW - Obesity
KW - Odds Ratio
KW - Polymorphism, Single Nucleotide
KW - Proprotein Convertase 1
AB - Polymorphisms rs6232 and rs6234/rs6235 in PCSK1 have been associated with extreme obesity [e.g. body mass index (BMI) ≥ 40 kg/m(2)], but their contribution to common obesity (BMI ≥ 30 kg/m(2)) and BMI variation in a multi-ethnic context is unclear. To fill this gap, we collected phenotypic and genetic data in up to 331 175 individuals from diverse ethnic groups. This process involved a systematic review of the literature in PubMed, Web of Science, Embase and the NIH GWAS catalog complemented by data extraction from pre-existing GWAS or custom-arrays in consortia and single studies. We employed recently developed global meta-analytic random-effects methods to calculate summary odds ratios (OR) and 95% confidence intervals (CIs) or beta estimates and standard errors (SE) for the obesity status and BMI analyses, respectively. Significant associations were found with binary obesity status for rs6232 (OR = 1.15, 95% CI 1.06-1.24, P = 6.08 × 10(-6)) and rs6234/rs6235 (OR = 1.07, 95% CI 1.04-1.10, P = 3.00 × 10(-7)). Similarly, significant associations were found with continuous BMI for rs6232 (β = 0.03, 95% CI 0.00-0.07; P = 0.047) and rs6234/rs6235 (β = 0.02, 95% CI 0.00-0.03; P = 5.57 × 10(-4)). Ethnicity, age and study ascertainment significantly modulated the association of PCSK1 polymorphisms with obesity. In summary, we demonstrate evidence that common gene variation in PCSK1 contributes to BMI variation and susceptibility to common obesity in the largest known meta-analysis published to date in genetic epidemiology.

VL - 24
IS - 12
ER -