Please use this identifier to cite or link to this item: https://doi.org/10.1371/journal.pone.0006827
Title: Powerful bivariate Genome-wide association analyses suggest the SOX6 gene influencing both obesity and osteoporosis phenotypes in males
Authors: Liu Y.-Z.
Pei Y.-F.
Liu J.-F.
Yang F.
Guo Y.
Zhang L.
Liu X.-G. 
Yan H.
Wang L.
Zhang Y.-P.
Levy S.
Recker R.R.
Deng H.-W.
Keywords: transcription factor Sox6
SOX6 protein, human
transcription factor Sox
adult
article
body mass
bone density
Caucasian
chondrogenesis
controlled study
family
female
femur neck
gene identification
genetic association
genotype
human
insulin resistance
intron
major clinical study
male
obesity
osteoporosis
pathogenesis
phenotype
single nucleotide polymorphism
aged
cohort analysis
genetics
middle aged
obesity
osteoporosis
Adult
Aged
Cohort Studies
Female
Genome-Wide Association Study
Humans
Male
Middle Aged
Obesity
Osteoporosis
Phenotype
Polymorphism, Single Nucleotide
SOXD Transcription Factors
Issue Date: 2009
Citation: Liu Y.-Z., Pei Y.-F., Liu J.-F., Yang F., Guo Y., Zhang L., Liu X.-G., Yan H., Wang L., Zhang Y.-P., Levy S., Recker R.R., Deng H.-W. (2009). Powerful bivariate Genome-wide association analyses suggest the SOX6 gene influencing both obesity and osteoporosis phenotypes in males. PLoS ONE 4 (8) : e6827. ScholarBank@NUS Repository. https://doi.org/10.1371/journal.pone.0006827
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 ?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 6.82� -7 and 1.47� -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 ?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 coregulation of obesity and osteoporosis. � 2009 Liu et al.
Source Title: PLoS ONE
URI: https://scholarbank.nus.edu.sg/handle/10635/161830
ISSN: 19326203
DOI: 10.1371/journal.pone.0006827
Appears in Collections:Staff Publications
Elements

Show full item record
Files in This Item:
File Description SizeFormatAccess SettingsVersion 
10_1371_journal_pone_0006827.pdf126.55 kBAdobe PDF

OPEN

NoneView/Download

SCOPUSTM   
Citations

64
checked on Dec 9, 2019

Page view(s)

10
checked on Dec 5, 2019

Google ScholarTM

Check

Altmetric


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.