NRXN3 is a novel locus for waist circumference: a genome-wide association study from the CHARGE Consortium

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 stag...

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Bibliographic Details
Published in:PLoS genetics 2009-06, Vol.5 (6), p.e1000539-e1000539
Main Authors: Heard-Costa, Nancy L, Zillikens, M Carola, Monda, Keri L, Johansson, Asa, Harris, Tamara B, Fu, Mao, Haritunians, Talin, Feitosa, Mary F, Aspelund, Thor, Eiriksdottir, Gudny, Garcia, Melissa, Launer, Lenore J, Smith, Albert V, Mitchell, Braxton D, McArdle, Patrick F, Shuldiner, Alan R, Bielinski, Suzette J, Boerwinkle, Eric, Brancati, Fred, Demerath, Ellen W, Pankow, James S, Arnold, Alice M, Chen, Yii-Der Ida, Glazer, Nicole L, McKnight, Barbara, Psaty, Bruce M, Rotter, Jerome I, Amin, Najaf, Campbell, Harry, Gyllensten, Ulf, Pattaro, Cristian, Pramstaller, Peter P, Rudan, Igor, Struchalin, Maksim, Vitart, Veronique, Gao, Xiaoyi, Kraja, Aldi, Province, Michael A, Zhang, Qunyuan, Atwood, Larry D, Dupuis, Josée, Hirschhorn, Joel N, Jaquish, Cashell E, O'Donnell, Christopher J, Vasan, Ramachandran S, White, Charles C, Aulchenko, Yurii S, Estrada, Karol, Hofman, Albert, Rivadeneira, Fernando, Uitterlinden, André G, Witteman, Jacqueline C M, Oostra, Ben A, Kaplan, Robert C, Gudnason, Vilmundur, O'Connell, Jeffrey R, Borecki, Ingrid B, van Duijn, Cornelia M, Cupples, L Adrienne, Fox, Caroline S, North, Kari E
Format: Article
Language:English
Subjects:
Aged
Body Mass Index
Cellular proteins
Cohort Studies
European Continental Ancestry Group - genetics
Female
Genes
Genetic aspects
Genetic Predisposition to Disease
Genetics and Genomics/Complex Traits
Genome-Wide Association Study
Health aspects
Health risk assessment
Humans
Male
Medical research
MEDICIN
MEDICINE
Middle Aged
Nerve Tissue Proteins - genetics
Nutrition/Obesity
Obesity
Obesity - genetics
Physiological aspects
Polymorphism, Single Nucleotide
Risk factors
Single nucleotide polymorphisms
Studies
Waist Circumference
Weight control
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Summary: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 = 6.4x10(-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 = 5.3x10(-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 = 7.4x10(-6), 0.024 z-score units (0.10 kg/m(2)) per copy of the G allele] and the risk of obesity (odds ratio 1.13, 95% CI 1.07-1.19; p = 3.2x10(-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.
ISSN:1553-7404
1553-7390
1553-7404
DOI:10.1371/journal.pgen.1000539