NRXN3 Is a Novel Locus for Waist Circumference: A Genome-Wide Association Study from the CHARGE Consortium

被引：204

作者：

Heard-Costa, Nancy L. ^{[1
]}

Zillikens, M. Carola ^{[2
]}

Monda, Keri L. ^{[3
]}

Johansson, Asa ^{[4
]}

Harris, Tamara B. ^{[5
]}

Fu, Mao ^{[6
]}

Haritunians, Talin ^{[7
]}

Feitosa, Mary F. ^{[8
]}

Aspelund, Thor ^{[9
,10
,11
]}

Eiriksdottir, Gudny ^{[9
,10
]}

Garcia, Melissa ^{[5
]}

Launer, Lenore J. ^{[5
]}

Smith, Albert V. ^{[9
,10
]}

Mitchell, Braxton D. ^{[6
]}

McArdle, Patrick F. ^{[6
]}

Shuldiner, Alan R. ^{[6
]}

Bielinski, Suzette J. ^{[12
]}

Boerwinkle, Eric ^{[13
,14
]}

Brancati, Fred ^{[15
]}

Demerath, Ellen W. ^{[16
]}

Pankow, James S. ^{[16
]}

Arnold, Alice M. ^{[17
]}

Chen, Yii-Der Ida ^{[7
]}

Glazer, Nicole L. ^{[18
]}

McKnight, Barbara ^{[17
]}

Psaty, Bruce M. ^{[19
]}

Rotter, Jerome I. ^{[7
]}

Amin, Najaf ^{[20
]}

Campbell, Harry ^{[21
]}

Gyllensten, Ulf ^{[4
]}

Pattaro, Cristian ^{[22
]}

Pramstaller, Peter P. ^{[22
,23
,24
]}

Rudan, Igor ^{[21
,25
,26
]}

Struchalin, Maksim ^{[20
]}

Vitart, Veronique ^{[27
]}

Gao, Xiaoyi ^{[8
]}

Kraja, Aldi ^{[8
]}

Province, Michael A. ^{[8
]}

Zhang, Qunyuan ^{[8
]}

Atwood, Larry D. ^{[1
]}

Dupuis, Josee ^{[28
]}

Hirschhorn, Joel N. ^{[29
,30
,31
]}

Jaquish, Cashell E. ^{[32
]}

O'Donnell, Christopher J. ^{[33
]}

Vasan, Ramachandran S. ^{[34
]}

White, Charles C. ^{[28
]}

Aulchenko, Yurii S. ^{[20
]}

Estrada, Karol ^{[2
]}

Hofman, Albert ^{[20
]}

Rivadeneira, Fernando ^{[2
,20
]}

机构：

[1] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA

[2] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands

[3] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA

[4] Uppsala Univ, Dept Genet & Pathol, Uppsala, Sweden

[5] NIA, Lab Epidemiol Demog & Biometry, Intramural Res Program, Bethesda, MD 20892 USA

[6] Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, Baltimore, MD 21201 USA

[7] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA

[8] Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA

[9] Iceland Heart Assoc, Heart Prevent Clin, Kopavogur, Iceland

[10] Iceland Heart Assoc, Res Inst, Kopavogur, Iceland

[11] Univ Iceland, Reykjavik, Iceland

[12] Mayo Clin, Div Epidemiol, Rochester, MN USA

[13] Univ Texas Houston, Hlth Sci Ctr, Ctr Human Genet, Houston, TX USA

[14] Univ Texas Houston, Hlth Sci Ctr, Inst Mol Med, Houston, TX USA

[15] Johns Hopkins Univ, Dept Med & Epidemiol, Baltimore, MD USA

[16] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA

[17] Univ Washington, Dept Biostat, Seattle, WA 98195 USA

[18] Univ Washington, Dept Internal Med, Seattle, WA 98195 USA

[19] Univ Washington, Dept Epidemiol Med & Hlth Serv, Seattle, WA 98195 USA

[20] Erasmus Univ, Dept Epidemiol & Biostat, Med Ctr, NL-3000 DR Rotterdam, Netherlands

[21] Univ Edinburgh, Sch Med, Dept Publ Hlth Sci, Edinburgh, Midlothian, Scotland

[22] European Acad Bozen Bolzano, Inst Med Genet, Bolzano, Italy

[23] Univ Lubeck, Dept Neurol, Lubeck, Germany

[24] Cent Reg Hosp, Dept Neurol, Bolzano, Italy

[25] Univ Split, Sch Med, Croatian Ctr Global Hlth, Split, Croatia

[26] Univ Hosp Sestre Milosrdnice, Inst Clin Med Res, Zagreb, Croatia

[27] Inst Genet & Mol Med, Human Genet Unit, Edinburgh, Midlothian, Scotland

[28] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA

[29] Harvard Univ, Sch Med, Program Genom, Boston, MA USA

[30] Harvard Univ, Sch Med, Div Endocrinol, Boston, MA USA

[31] Harvard Univ, Sch Med, Div Genet, Boston, MA USA

[32] NHLBI, Div Prevent & Populat Sci, Bethesda, MD 20892 USA

[33] NHLBI, Div Intramural Res, Framingham Heart Study, Framingham, MA USA

[34] Boston Univ, Sch Med, Boston, MA 02118 USA

[35] Erasmus Univ, Dept Clin Genet, Med Ctr, NL-3000 DR Rotterdam, Netherlands

[36] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA

[37] Harvard Univ, Sch Med, Dept Med, Div Endocrinol Diabet & Metab, Boston, MA USA

来源：

PLOS GENETICS | 2009年 / 5卷 / 06期

关键词：

BODY-FAT DISTRIBUTION; DEPENDENT DIABETES-MELLITUS; FTO GENE; ADULT OBESITY; MASS INDEX; EXPRESSION; LINKAGE; VARIANT; MC4R; RISK;

D O I：

10.1371/journal.pgen.1000539

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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.

引用

页数：9

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