Genetic variation in TRPS1 may regulate hip geometry as well as bone mineral density

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• 作者：Cheryl L. Ackert-Bicknell^a ; ^{cheryl.ackertb@jax.org} ; Serkalem Demissie^b ; ^{demissie@bu.edu} ; Shirng-Wern Tsaih^a ; ¹ ; ^{stsaih@mcw.edu} ; Wesley G. Beamer^a ; ^{Wesley.Beamer@jax.org} ; L. Adrienne Cupples^b ; ^{adrienne@bu.edu} ; Beverly J. Paigen^a ; ^{bev.paigen@jax.org} ; Yi-Hsiang Hsu^c ; ^{yihsianghsu@hsl.harvard.edu} ; Douglas P. Kiel^c ; ^{kiel@hsl.harvard.edu} ; David Karasik^c ; ^{karasik@hsl.harvard.edu}
• 关键词：(TRPS1) ; trichorhinophalangeal syndrome I ; (BMD) ; bone mineral density ; (GWAS) ; genome wide association study ; (SNP) ; single nucleotide polymorphism ; (NNW) ; narrow neck width ; (FNL) ; femoral neck length ; (NSA) ; femoral neck-shaft angle ; (FN) ; femoral neck
• 刊名：Bone
• 出版年：2012
• 期刊代码：39_87563282
• 类别：med
• 出版时间：May, 2012
• 卷：50
• 期：5
• 页码：1188-1195
• 文件大小：510 K

摘要

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 24 cM. 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 10 kb 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 脳 10^鈭?#xA0;5, adjusted P = 2.15 脳 10^鈭?#xA0;3; rs7002384, P = 5.5 脳 10^鈭?#xA0;4, adjusted P = 01.38 脳 10^鈭?#xA0;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.