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通过与全基因组 SNPs 的连锁分析对骨质疏松症相关特征进行精细化 QTL 分析:弗雷明汉 SHARE。

Refined QTLs of osteoporosis-related traits by linkage analysis with genome-wide SNPs: Framingham SHARe.

机构信息

Hebrew SeniorLife Institute for Aging Research and Harvard Medical School, Boston, MA 02131, USA.

出版信息

Bone. 2010 Apr;46(4):1114-21. doi: 10.1016/j.bone.2010.01.001. Epub 2010 Jan 11.

Abstract

Genome-wide association studies (GWAS) using high-density array of single-nucleotide polymorphisms (SNPs) offer an unbiased strategy to identify new candidate genes for osteoporosis. We used a subset of autosomal SNPs from the Affymetrix 500K+50K SNP GeneChip marker set to examine genetic linkage with multiple highly heritable osteoporosis-related traits, including BMD of the hip and spine, heel ultrasound (attenuation and speed of sound), and geometric indices of the hip, in two generations from the Framingham Osteoporosis Study. Variance component linkage analysis was performed using normalized residuals (adjusted for age, height, BMI, and estrogen status in women). Multipoint linkage analyses produced LOD scores > or =3.0 for BMD on chromosomes (chr.) 9 and 11 and for ultrasound speed of sound on chr. 5. Hip geometric traits were linked with higher LOD scores, such as with shaft width on chr. 4 (LOD=3.9) and chr. 16 (LOD=3.8) and with shaft section modulus on chr. 22 (LOD=4.0). LOD score > or =5.0 was obtained for femoral neck width on chr. 7. In conclusion, with an SNP-based linkage approach, we identified several novel potential QTLs and confirmed previously identified chromosomal regions linked to bone mass and geometry. Subsequent focus on the spectrum of genetic polymorphisms in these refined regions may contribute to finding variants predisposing to osteoporosis.

摘要

全基因组关联研究(GWAS)使用高密度单核苷酸多态性(SNP)阵列提供了一种无偏策略来识别骨质疏松症的新候选基因。我们使用来自 Affymetrix 500K+50K SNP GeneChip 标记集的常染色体 SNP 的子集,检查与多种高度遗传的骨质疏松相关特征的遗传连锁,包括髋部和脊柱的 BMD、足跟超声(衰减和声音速度)和髋部的几何指数,在 Framingham 骨质疏松症研究的两代人中。方差分量连锁分析使用标准化残差(调整年龄、身高、BMI 和女性雌激素状态)进行。多点连锁分析在染色体(chr.)9 和 11 上的 BMD 和 chr.5 上的超声速度产生了 LOD 分数>或=3.0。髋部几何特征与更高的 LOD 分数相关,例如在 chr.4(LOD=3.9)和 chr.16(LOD=3.8)上的杆宽和 chr.22 上的杆截面模数(LOD=4.0)。在 chr.7 上获得了股骨颈宽度的 LOD 分数>或=5.0。总之,通过基于 SNP 的连锁方法,我们确定了几个新的潜在 QTL,并证实了先前与骨量和几何形状相关的染色体区域。随后关注这些精细区域中遗传多态性的范围可能有助于发现易患骨质疏松症的变异。

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