Study Report - GWAS of obesity and osteoporosis in Caucasians (HGVST502)
Bookmark
Explore Study in Browser| Identifier | HGVST502 | ||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Study name | GWAS of obesity and osteoporosis in Caucasians | ||||||||||||||||||||
| Total p-values imported | 2 | ||||||||||||||||||||
| Phenotype(s) tested | Obesity and osteoporosis (body mass index and bone mineral density, males) |
||||||||||||||||||||
| Study design | Quantitative trait analysis with replication | ||||||||||||||||||||
| Genotype platforms |
Affymetrix 379,319 | ||||||||||||||||||||
| Abstract | BACKGROUND: Current genome-wide association studies (GWAS) are normally implemented in a univariate framework and analyze different phenotypes in isolation. This univariate approach ignores the potential genetic correlation between important disease traits. Hence this approach is difficult to detect pleiotropic genes, which may exist for obesity and osteoporosis, two common diseases of major public health importance that are closely correlated genetically. PRINCIPAL FINDINGS: To identify such pleiotropic genes and the key mechanistic links between the two diseases, we here performed the first bivariate GWAS of obesity and osteoporosis. We searched for genes underlying co-variation of the obesity phenotype, body mass index (BMI), with the osteoporosis risk phenotype, hip bone mineral density (BMD), scanning approximately 380,000 SNPs in 1,000 unrelated homogeneous Caucasians, including 499 males and 501 females. We identified in the male subjects two SNPs in intron 1 of the SOX6 (SRY-box 6) gene, rs297325 and rs4756846, which were bivariately associated with both BMI and hip BMD, achieving p values of 6.82x10(-7) and 1.47x10(-6), respectively. The two SNPs ranked at the top in significance for bivariate association with BMI and hip BMD in the male subjects among all the approximately 380,000 SNPs examined genome-wide. The two SNPs were replicated in a Framingham Heart Study (FHS) cohort containing 3,355 Caucasians (1,370 males and 1,985 females) from 975 families. In the FHS male subjects, the two SNPs achieved p values of 0.03 and 0.02, respectively, for bivariate association with BMI and femoral neck BMD. Interestingly, SOX6 was previously found to be essential to both cartilage formation/chondrogenesis and obesity-related insulin resistance, suggesting the gene's dual role in both bone and fat. CONCLUSIONS: Our findings, together with the prior biological evidence, suggest the SOX6 gene's importance in co-regulation of obesity and osteoporosis. | ||||||||||||||||||||
| Submission information |
|
||||||||||||||||||||
Author communication  |
|
||||||||||||||||||||
| Related links |
NHGRI GWAS catalog study annotation for HGVST502 |
||||||||||||||||||||
| 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 | ||||||||||||||||||||
| Related citations |
Liu YZ, Pei YF, Liu JF et al.
Powerful bivariate genome-wide association analyses suggest the SOX6 gene influencing both obesity and osteoporosis phenotypes in males. PLoS One 2009 Aug 28;4(8):e6827
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 |
