Genome-wide pleiotropy of osteoporosis-related phenotypes: the Framingham Study.
Genome-wide pleiotropy of osteoporosis-related phenotypes: the Framingham Study.
复制标题
DOI：
10.1002/jbmr.38
复制
发表时间：
2010-07
影响因子：
6.2
通讯作者：
Demissie, Serkalem
中科院分区：
文献类型：
--
作者：
Karasik, David;Hsu, Yi-Hsiang;Zhou, Yanhua;Cupples, L. Adrienne;Kiel, Douglas P.;Demissie, Serkalem
关键词：
全基因组关联研究提供了一个公正的方法来确定新的候选基因的骨质疏松症。我们在Frachial Osteoporosis Study中检查了Affyoung 500 K +50 K SNP基因芯片标记集与各种骨骼部位多个骨质疏松相关性状的相关性，包括骨矿物质密度（BMD，髋关节和脊柱），足跟超声和髋关节几何指数。我们评估了2073名女性（平均年龄65岁）的433，510个单核苷酸多态性（SNP），这些女性来自两代同堂的家庭。方差分量分析估计骨性状之间的表型、遗传和环境相关（ρP、ρG和ρE）。线性混合效应模型被用来测试SNPs和多变量调整性状值之间的关联。我们在名义显著性阈值α = 0.01下评估了与成对性状相关的SNP比例。我们发现相关SNP的比例与ρP和ρG之间存在显著相关性（r分别为0.91和0.84），但与ρE之间的相关性要低得多（r = 0.38）。因此，例如，髋关节和脊柱BMD有6.8%的共同相关SNP，对应于它们之间的ρP = 0.55和ρG = 0.66。与BMD和任何髋关节几何特征（例如，股骨颈和股骨干宽度、截面模量、颈干角和颈长）相关的SNP较少; BMD和几何特征之间的ρG范围为-0.24至+0.40。总之，我们研究了基于全基因组关联的糖尿病相关性状之间的关系。骨定量表型之间的大部分相似性可能归因于基因的多效性效应。这些知识可能有助于确定骨质疏松症遗传学研究中使用的最佳表型。© 2010美国骨与矿物质研究学会。
Genome-wide association studies offer an unbiased approach to identify new candidate genes for osteoporosis. We examined the Affymetrix 500K + 50K SNP GeneChip marker sets for associations with multiple osteoporosis-related traits at various skeletal sites, including bone mineral density (BMD, hip and spine), heel ultrasound, and hip geometric indices in the Framingham Osteoporosis Study. We evaluated 433,510 single-nucleotide polymorphisms (SNPs) in 2073 women (mean age 65 years), members of two-generational families. Variance components analysis was performed to estimate phenotypic, genetic, and environmental correlations (ρP, ρG, and ρE) among bone traits. Linear mixed-effects models were used to test associations between SNPs and multivariable-adjusted trait values. We evaluated the proportion of SNPs associated with pairs of the traits at a nominal significance threshold α = 0.01. We found substantial correlation between the proportion of associated SNPs and the ρP and ρG (r = 0.91 and 0.84, respectively) but much lower with ρE (r = 0.38). Thus, for example, hip and spine BMD had 6.8% associated SNPs in common, corresponding to ρP = 0.55 and ρG = 0.66 between them. Fewer SNPs were associated with both BMD and any of the hip geometric traits (eg, femoral neck and shaft width, section moduli, neck shaft angle, and neck length); ρG between BMD and geometric traits ranged from −0.24 to +0.40. In conclusion, we examined relationships between osteoporosis-related traits based on genome-wide associations. Most of the similarity between the quantitative bone phenotypes may be attributed to pleiotropic effects of genes. This knowledge may prove helpful in defining the best phenotypes to be used in genetic studies of osteoporosis. © 2010 American Society for Bone and Mineral Research.
登录
查看更多内容
影响因子：
2.1
作者：
Deng, HW;Mahaney, MC;Recker, RR
通讯作者：
Recker, RR
影响因子：
6.2
作者：
Howard, GM;Nguyen, TV;Eisman, JA
通讯作者：
Eisman, JA
影响因子：
6.2
作者：
Andrew, T;Antioniades, L;Spector, TD
通讯作者：
Spector, TD
影响因子：
2.1
作者：
Jung, Jeesun;Zhong, Ming;Fan, Ruzong
通讯作者：
Fan, Ruzong
影响因子：
2.1
作者：
Blangero, J;Williams, JT;Almasy, L
通讯作者：
Almasy, L