Genetic variation in TRPS1 may regulate hip geometry as well as bone mineral density. Bone 2012 May;50(5):1188-95
Date
02/07/2012Pubmed ID
22306695Pubmed Central ID
PMC3322322DOI
10.1016/j.bone.2012.01.011Scopus ID
2-s2.0-84859426283 (requires institutional sign-in at Scopus site) 10 CitationsAbstract
Trps1 has been proposed as a candidate gene for a mouse bone mineral density (BMD) QTL on Chromosome (Chr) 15, but it remained unclear if this gene was associated with BMD in humans. We used newly available data and advanced bioinformatics techniques to confirm that Trps1 is the most likely candidate gene for the mouse QTL. In short, by combining the raw genetic mapping data from two F2 generation crosses of inbred strains of mice, we narrowed the 95% confidence interval of this QTL down to the Chr 15 region spanning from 6 to 24cM. This region contains 131 annotated genes. Using block haplotyping, all other genes except Trps1 were eliminated as candidates for this QTL. We then examined associations of 208 SNPs within 10kb of TRPS1 with BMD and hip geometry, using human genome-wide association study (GWAS) data from the GEFOS consortium. After correction for multiple testing, six TRPS1 SNPs were significantly associated with femoral neck BMD (P=0.0015-0.0019; adjusted P=0.038-0.048). We also found that three SNPs were highly associated with femoral neck width in women (rs10505257, P=8.6×10(-5), adjusted P=2.15×10(-3); rs7002384, P=5.5×10(-4), adjusted P=01.38×10(-2)). In conclusion, we demonstrated that combining association studies in humans with murine models provides an efficient strategy to identify new candidate genes for bone phenotypes.
Author List
Ackert-Bicknell CL, Demissie S, Tsaih SW, Beamer WG, Cupples LA, Paigen BJ, Hsu YH, Kiel DP, Karasik DAuthor
Shirng-Wern Tsaih Research Scientist II in the Obstetrics and Gynecology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsBone Density
Chromosomes, Mammalian
Crosses, Genetic
DNA-Binding Proteins
Female
GATA Transcription Factors
Genetic Association Studies
Genetic Variation
Genome-Wide Association Study
Haplotypes
Hip
Humans
Lod Score
Male
Mice
Phenotype
Polymorphism, Single Nucleotide
Quantitative Trait Loci
Repressor Proteins
Transcription Factors
