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
Autor: | Nead, Kevin T., Li, Aihua, Wehner, Mackenzie R., Neupane, Binod, Gustafsson, Stefan, Butterworth, Adam, Engert, James C., Davis, A. Darlene, Hegele, Robert A., Miller, Ruby, den Hoed, Marcel, Khaw, Kay-Tee, Kilpeläinen, Tuomas O., Wareham, Nick, Edwards, Todd L., Hallmans, Göran, Varga, TiborV., Kardia, SharonL.R., Smith, Jennifer A., Zhao, Wei, Faul, Jessica D., Weir, David, Mi, Jie, Xi, Bo, Quinteros, Samuel Canizales, Cooper, Cyrus, Sayer, Avan Aihie, Jameson, Karen, Grøntved, Anders, Fornage, Myriam, Sidney, Stephen, Hanis, Craig L., Highland, Heather M., Häring, Hans-Ulrich, Heni, Martin, Lasky-Su, Jessica, Weiss, Scott T., Gerhard, Glenn S., Still, Christopher, Melka, Melkaey M., Pausova, Zdenka, Paus, Tomáš, Grant, Struan F.A., Hakonarson, Hakon, Price, R Arlen, Wang, Kai, Scherag, Andre, Hebebrand, Johannes, Hinney, Anke, BioBank Japan, AGEN-BMI, GIANT Consortium, Franks, Paul W., Frayling, Timothy M., McCarthy, Mark I., Hirschhorn, Joel N., Loos, Ruth, Ingelsson, Erik, Gerstein, Hertzel C., Yusuf, Salim, Beyene, Joseph, Anand, Sonia S., Meyre, David |
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Jazyk: | angličtina |
Rok vydání: | 2015 |
Předmět: |
Medizin
Genome-wide association study Context (language use) Biology Bioinformatics Polymorphism Single Nucleotide Body Mass Index Proprotein Convertase 1/genetics Genetics medicine Odds Ratio Humans Genetic Predisposition to Disease Obesity Molecular Biology Genetics (clinical) Alleles Association Studies Articles Genetic Variation General Medicine Odds ratio Obesity/diagnosis medicine.disease Confidence interval Genetic epidemiology Proprotein Convertase 1 Meta-analysis Body mass index Demography |
Zdroj: | Nead, K T, Li, A, Wehner, M R, Neupane, B, Gustafsson, S, Butterworth, A, Engert, J C, Davis, A D, Hegele, R A, Miller, R, den Hoed, M, Khaw, K-T, Kilpeläinen, T O, Wareham, N, Edwards, T L, Hallmans, G, Varga, T V, Kardia, S L R, Smith, J A, Zhao, W, Faul, J D, Weir, D, Mi, J, Xi, B, Quinteros, S C, Cooper, C, Sayer, A A, Jameson, K, Grøntved, A, Fornage, M, Sidney, S, Hanis, C L, Highland, H M, Häring, H-U, Heni, M, Lasky-Su, J, Weiss, S T, Gerhard, G S, Still, C, Melka, M M, Pausova, Z, Paus, T, Grant, S F A, Hakonarson, H, Price, R A, Wang, K, Scherag, A, Hebebrand, J, Hinney, A, Franks, P W & BioBank Japan, AGEN-BMI, GIANT Consortium 2015, ' 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 ', Human Molecular Genetics, vol. 24, no. 12, pp. 3582-3594 . https://doi.org/10.1093/hmg/ddv097 Hum. Mol. Genet. 24, 3582-3594 (2015) |
Popis: | 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. |
Databáze: | OpenAIRE |
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