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Study Report - GWAS of waist circumference in individuals of Caucasian descent (HGVST364)| HGVbaseG2P identifier | HGVST364 | ||||||||||||||||||||
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| Study name | GWAS of waist circumference in individuals of Caucasian descent | ||||||||||||||||||||
| Phenotype(s) tested | Waist circumference |
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| Study design | Quantitative trait analysis with replication | ||||||||||||||||||||
| Genotype Platforms |
Affymetrix & Illumina up to 512,349 | ||||||||||||||||||||
| 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. | ||||||||||||||||||||
| Submission information |
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| Cross-references |
NHGRI GWAS catalog study annotation for HGVST364 |
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| Background | Not supplied | ||||||||||||||||||||
| Objectives | Not supplied | ||||||||||||||||||||
| Key results | Not supplied | ||||||||||||||||||||
| Conclusions | Not supplied | ||||||||||||||||||||
| Reason for study size | Not supplied | ||||||||||||||||||||
| Study power | Not supplied | ||||||||||||||||||||
| Sources of bias | Not supplied | ||||||||||||||||||||
| Limitations | Not supplied | ||||||||||||||||||||
| Acknowledgements | Not supplied | ||||||||||||||||||||
| Other citations |
Hindorff LA, Sethupathy P, Junkins HA et al.
Potential etiologic and functional implications of genome-wide association loci for human diseases and traits. Proceedings of the National Academy of Sciences U S A. 2009 May 27
Heard-Costa NL, Zillikens MC, Monda KL et al.
NRXN3 is a novel locus for waist circumference: a genome-wide association study from the CHARGE Consortium. PLoS genetics 2009;5(6):e1000539 |
