title: NRXN3 is a novel locus for waist circumference: a genome-wide association study from the CHARGE Consortium.
abstract: 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.
authors: Department of Neurology, Boston University School of Medicine, Boston, Massachusetts, United States of America.
authors: Nancy L
authors: NL
authors: Heard-Costa
authors: M Carola
authors: MC
authors: Zillikens
authors: Keri L
authors: KL
authors: Monda
authors: Asa
authors: A
authors: Johansson
authors: Tamara B
authors: TB
authors: Harris
authors: Mao
authors: M
authors: Fu
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authors: Haritunians
authors: Mary F
authors: MF
authors: Feitosa
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authors: Aspelund
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authors: Eiriksdottir
authors: Melissa
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authors: Garcia
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authors: Launer
authors: Albert V
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authors: Patrick F
authors: PF
authors: McArdle
authors: Alan R
authors: AR
authors: Shuldiner
authors: Suzette J
authors: SJ
authors: Bielinski
authors: Eric
authors: E
authors: Boerwinkle
authors: Fred
authors: F
authors: Brancati
authors: Ellen W
authors: EW
authors: Demerath
authors: James S
authors: JS
authors: Pankow
authors: Alice M
authors: AM
authors: Arnold
authors: Yii-Der Ida
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authors: Chen
authors: Nicole L
authors: NL
authors: Glazer
authors: Barbara
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authors: McKnight
authors: Bruce M
authors: BM
authors: Psaty
authors: Jerome I
authors: JI
authors: Rotter
authors: Najaf
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authors: Amin
authors: Harry
authors: H
authors: Campbell
authors: Ulf
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authors: Gyllensten
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authors: Pattaro
authors: Peter P
authors: PP
authors: Pramstaller
authors: Igor
authors: I
authors: Rudan
authors: Maksim
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authors: Struchalin
authors: Veronique
authors: V
authors: Vitart
authors: Xiaoyi
authors: X
authors: Gao
authors: Aldi
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authors: Kraja
authors: Michael A
authors: MA
authors: Province
authors: Qunyuan
authors: Q
authors: Zhang
authors: Larry D
authors: LD
authors: Atwood
authors: Josée
authors: J
authors: Dupuis
authors: Joel N
authors: JN
authors: Hirschhorn
authors: Cashell E
authors: CE
authors: Jaquish
authors: Christopher J
authors: CJ
authors: O'Donnell
authors: Ramachandran S
authors: RS
authors: Vasan
authors: Charles C
authors: CC
authors: White
authors: Yurii S
authors: YS
authors: Aulchenko
authors: Karol
authors: K
authors: Estrada
authors: Albert
authors: A
authors: Hofman
authors: Fernando
authors: F
authors: Rivadeneira
authors: André G
authors: AG
authors: Uitterlinden
authors: Jacqueline C M
authors: JC
authors: Witteman
authors: Ben A
authors: BA
authors: Oostra
authors: Robert C
authors: RC
authors: Kaplan
authors: Vilmundur
authors: V
authors: Gudnason
authors: Jeffrey R
authors: JR
authors: O'Connell
authors: Ingrid B
authors: IB
authors: Borecki
authors: Cornelia M
authors: CM
authors: van Duijn
authors: L Adrienne
authors: LA
authors: Cupples
authors: Caroline S
authors: CS
authors: Fox
authors: Kari E
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authors: North
mesh_terms: D000368:Aged; D015992:Body Mass Index; D015331:Cohort Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009765:Obesity / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D055105:Waist Circumference; D044465:White People / Q000235:genetics
chemical_list: D009419:Nerve Tissue Proteins; C082354:neurexin IIIalpha