@article {12129,
	title = {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.},
	journal = {Human Molecular Genetics},
	volume = {24},
	year = {2015},
	pages = {3582-3594},
	abstract = {<p>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 {\texttimes} 10(-6)) and rs6234/rs6235 (OR = 1.07, 95\% CI 1.04-1.10, P = 3.00 {\texttimes} 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 {\texttimes} 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. </p>},
	keywords = {Alleles, Body Mass Index, Genetic Predisposition to Disease, Genetic Variation, Humans, Obesity, Odds Ratio, Polymorphism, Single Nucleotide, Proprotein Convertase 1},
	issn = {1460-2083},
	doi = {10.1093/hmg/ddv097},
	author = {Nead, Kevin T and Li, Aihua and Wehner, Mackenzie R and Neupane, Binod and Gustafsson, Stefan and Adam S Butterworth and Engert, James C and Davis, A Darlene and Hegele, Robert A and Miller, Ruby and den Hoed, Marcel and Khaw, Kay-Tee and Kilpel{\"a}inen, Tuomas O and Wareham, Nick and Edwards, Todd L and Hallmans, G{\"o}ran and Varga, Tibor V and Sharon L R Kardia and Smith, Jennifer A and Zhao, Wei and Jessica Faul and David R Weir and Mi, Jie and Xi, Bo and Quinteros, Samuel Canizales and Cooper, Cyrus and Sayer, Avan Aihie and Jameson, Karen and Gr{\o}ntved, Anders and Myriam Fornage and Stephen Sidney and Hanis, Craig L and Highland, Heather M and H{\"a}ring, Hans-Ulrich and Heni, Martin and Lasky-Su, Jessica and Weiss, Scott T and Gerhard, Glenn S and Still, Christopher and Melka, Melkaey M and Pausova, Zdenka and Paus, Tom{\'a}{\v s} and Grant, Struan F A and Hakonarson, Hakon and Price, R Arlen and Wang, Kai and Scherag, Andre and Hebebrand, Johannes and Hinney, Anke and Franks, Paul W and Timothy M Frayling and McCarthy, Mark I and Hirschhorn, Joel N and Ruth J F Loos and Ingelsson, Erik and Gerstein, Hertzel C and Yusuf, Salim and Beyene, Joseph and Anand, Sonia S and Meyre, David}
}
