Genetic risk score based on the lifetime prevalence of femoral fracture in 1632 consecutive Japanese autopsy cases
Genetic risk score based on the lifetime prevalence of femoral fracture in 1632 consecutive Japanese autopsy cases
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基于 1632 例连续日本尸检病例股骨骨折终生患病率的遗传风险评分
DOI：
10.1007/s00774-015-0718-7
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发表时间：
2016
影响因子：
3.3
通讯作者：
Hideki Ito
中科院分区：
文献类型：
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作者：
Heying Zhou;Seijiro Mori;Tatsuro Ishizaki;Masashi Tanaka;Kumpei Tanisawa;Makiko Naka-Mieno;Motoji Sawabe;Tomio Arai;Masaaki Muramatsu;Yoshiji Yamada;Hideki Ito
根据 924 例连续尸检的日本男性终生股骨骨折患病率，开发了遗传风险评分 (GRS)，用于预测骨折风险。对位于 62 个骨质疏松症易感基因中的总共 922 个非同义单核苷酸多态性 (SNP) 进行了基因分型，并评估了它们与尸检病例中股骨骨折患病率的关联。 GRS 值计算为风险等位基因计数的总和（未加权的 GRS）或根据逻辑回归系数估计的加权分数的总和（加权的 GRS）。 5 个 SNP（α-ʟ-iduronidasers3755955、C7orf58rs190543052、同源盒 C4rs75256744、含 G patch 结构域的基因 1rs2287679 和 Werner 综合征 2230009）显示与 924 名男性股骨骨折的患病率显着相关（P<0.05） 科目。未加权和加权 GRS 均足以预测骨折发生率；接受者操作特征曲线下的面积分别为 0.750 [95% 置信区间 (CI) 0.660–0.840] 和 0.770 (95% CI 0.681–0.859)。多元逻辑回归分析显示，相对于评分 <3 (n= 797)，骨折发生率与未加权 GRS ≥ 3 (n= 124) 之间关联的比值比 (OR) 为 8.39 (95% CI 4.22–16.69，P< 0.001)。同样，相对于分数 0-5 (n= 786)，加权 GRS 为 6-15 (n= 135) 的 OR 为 7.73 (95% CI 3.89-15.36，P< 0.001)。基于五个 SNP 的风险等位基因谱的 GRS 可以帮助识别高风险个体，并能够实施股骨骨折的预防措施。
A genetic risk score (GRS) was developed for predicting fracture risk based on lifetime prevalence of femoral fractures in 924 consecutive autopsies of Japanese males. A total of 922 non-synonymous single nucleotide polymorphisms (SNPs) located in 62 osteoporosis susceptibility genes were genotyped and evaluated for their association with the prevalence of femoral fracture in autopsy cases. GRS values were calculated as the sum of risk allele counts (unweighted GRS) or the sum of weighted scores estimated from logistic regression coefficients (weighted GRS). Five SNPs (α-ʟ-iduronidasers3755955,C7orf58rs190543052,homeobox C4rs75256744,G patch domain-containing gene 1rs2287679, andWerner syndromers2230009) showed a significant association (P< 0.05) with the prevalence of femoral fracture in 924 male subjects. Both the unweighted and weighted GRS adequately predicted fracture prevalence; areas under receiver-operating characteristic curves were 0.750 [95 % confidence interval (CI) 0.660–0.840] and 0.770 (95 % CI 0.681–0.859), respectively. Multiple logistic regression analysis revealed that the odds ratio (OR) for the association between fracture prevalence and unweighted GRS ≥3 (n= 124) was 8.39 (95 % CI 4.22–16.69,P< 0.001) relative to a score <3 (n= 797). Likewise, the OR for a weighted GRS of 6–15 (n= 135) was 7.73 (95 % CI 3.89–15.36,P< 0.001) relative to scores of 0–5 (n= 786). The GRS based on risk allele profiles of the five SNPs could help identify at-risk individuals and enable implementation of preventive measures for femoral fracture.