NRXN3 is a novel locus for waist circumference: a genome-wide association study from the CHARGE Consortium
| Autor: | Mao Fu, M. Carola Zillikens, Charles C. White, Ellen W. Demerath, Thor Aspelund, Talin Haritunians, Albert V. Smith, Cristian Pattaro, L. Adrienne Cupples, Xiaoyi Gao, Christopher J. O'Donnell, Jacqueline C.M. Witteman, Mary F. Feitosa, Lenore J. Launer, Veronique Vitart, Alan R. Shuldiner, Vilmundur Gudnason, Nicole L. Glazer, Robert C. Kaplan, Harry Campbell, Åsa Johansson, Bruce M. Psaty, André G. Uitterlinden, Karol Estrada, Eric Boerwinkle, Ingrid B. Borecki, Qunyuan Zhang, Yii-Der Ida Chen, Ben A. Oostra, Suzette J. Bielinski, Igor Rudan, Albert Hofman, Larry D. Atwood, Joel N. Hirschhorn, Melissa Garcia, Josée Dupuis, Tamara B. Harris, Jerome I. Rotter, Keri L. Monda, Barbara McKnight, Nancy L. Heard-Costa, Kari E. North, Cashell E. Jaquish, Maksim Struchalin, James S. Pankow, Yurii S. Aulchenko, Caroline S. Fox, Ramachandran S. Vasan, Fred Brancati, Najaf Amin, Peter P. Pramstaller, Alice M. Arnold, Braxton D. Mitchell, Ulf Gyllensten, Fernando Rivadeneira, Jeffrey R. O'Connell, Gudny Eiriksdottir, Cornelia M. van Duijn, Aldi T. Kraja, Patrick F. McArdle, Michael A. Province |
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| Přispěvatelé: | Internal Medicine, Epidemiology, Clinical Genetics |
| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: |
Male
Cancer Research Genome-wide association study Body Mass Index Cohort Studies 0302 clinical medicine Nutrition/Obesity Genetics(clinical) Genetics (clinical) 2. Zero hunger Genetics 0303 health sciences Middle Aged 3. Good health Female Waist Circumference Research Article medicine.medical_specialty Waist lcsh:QH426-470 030209 endocrinology & metabolism Single-nucleotide polymorphism Locus (genetics) Nerve Tissue Proteins Biology Genetics and Genomics/Complex Traits Polymorphism Single Nucleotide White People 03 medical and health sciences SDG 3 - Good Health and Well-being Internal medicine medicine Humans Genetic Predisposition to Disease Obesity Allele Molecular Biology Ecology Evolution Behavior and Systematics 030304 developmental biology Aged genome-wide association study waist circumference NRXN3 Odds ratio medicine.disease lcsh:Genetics Endocrinology Body mass index Genome-Wide Association Study |
| Zdroj: | PLoS Genetics, Vol 5, Iss 6, p e1000539 (2009) PLoS Genetics PLoS Genetics (print), 5(6). Public Library of Science Heard-Costa, N L, Zillikens, M C, Monda, K L, Johansson, A, Harris, T B, Fu, M, Haritunians, T, Feitosa, M F, Aspelund, T, Eiriksdottir, G, Garcia, M, Launer, L J, Smith, A V, Mitchell, B D, McArdle, P F, Shuldiner, A R, Bielinski, S J, Boerwinkle, E, Brancati, F, Demerath, E W, Pankow, J S, Arnold, A M, Chen, Y-D I, Glazer, N L, McKnight, B, Psaty, B M, Rotter, J I, Amin, N, Campbell, H, Gyllensten, U, Pattaro, C, Pramstaller, P P, Rudan, I, Struchalin, M, Vitart, V, Gao, X, Kraja, A, Province, M A, Zhang, Q, Atwood, L D, Dupuis, J, Hirschhorn, J N, Jaquish, C E, O'Donnell, C J, Vasan, R S, White, C C, Aulchenko, Y S, Estrada, K, Hofman, A, Rivadeneira, F, Uitterlinden, A G, Witteman, J C M, Oostra, B A, Kaplan, R C, Gudnason, V, O'Connell, J R, Borecki, I B, van Duijn, C M, Cupples, L A, Fox, C S & North, K E 2009, ' NRXN3 is a novel locus for waist circumference : a genome-wide association study from the CHARGE Consortium ', PLoS Genetics, vol. 5, no. 6, e1000539 . https://doi.org/10.1371/journal.pgen.1000539 |
| ISSN: | 1553-7404 1553-7390 1014-6997 |
| Popis: | Central abdominal fat is a strong risk factor for diabetes and cardiovascular disease. To identify common variants influencing central abdominal fat, we conducted a two-stage genome-wide association analysis for waist circumference (WC). In total, three loci reached genome-wide significance. In stage 1, 31,373 individuals of Caucasian descent from eight cohort studies confirmed the role of FTO and MC4R and identified one novel locus associated with WC in the neurexin 3 gene [NRXN3 (rs10146997, p = 6.4×10−7)]. The association with NRXN3 was confirmed in stage 2 by combining stage 1 results with those from 38,641 participants in the GIANT consortium (p = 0.009 in GIANT only, p = 5.3×10−8 for combined analysis, n = 70,014). Mean WC increase per copy of the G allele was 0.0498 z-score units (0.65 cm). This SNP was also associated with body mass index (BMI) [p = 7.4×10−6, 0.024 z-score units (0.10 kg/m2) per copy of the G allele] and the risk of obesity (odds ratio 1.13, 95% CI 1.07–1.19; p = 3.2×10−5 per copy of the G allele). The NRXN3 gene has been previously implicated in addiction and reward behavior, lending further evidence that common forms of obesity may be a central nervous system-mediated disorder. Our findings establish that common variants in NRXN3 are associated with WC, BMI, and obesity. Author Summary Obesity is a major health concern worldwide. In the past two years, genome-wide association studies of DNA markers known as SNPs (single nucleotide polymorphisms) have identified two novel genetic factors that may help scientists better understand why some people may be more susceptible to obesity. Similarly, this paper describes results from a large scale genome-wide association analysis for obesity susceptibility genes that includes 31,373 individuals from 8 separate studies. We uncovered a new gene influencing waist circumference, the neurexin 3 gene (NRXN3), which has been previously implicated in studies of addiction and reward behavior. These findings lend further evidence that our genes may influence our desire and consumption of food and, in turn, our susceptibility to obesity. |
| Databáze: | OpenAIRE |
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