Variants at APOE influence risk of deep and lobar intracerebral hemorrhage.
Variants at APOE influence risk of deep and lobar intracerebral hemorrhage.
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DOI：
10.1002/ana.22134
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发表时间：
2010-12
影响因子：
11.2
通讯作者：
Rosand, Jonathan
中科院分区：
文献类型：
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作者：
Biffi, Alessandro;Sonni, Akshata;Anderson, Christopher D.;Kissela, Brett;Jagiella, Jeremiasz M.;Schmidt, Helena;Jimenez-Conde, Jordi;Hansen, Bjorn M.;Fernandez-Cadenas, Israel;Cortellini, Lynelle;Ayres, Alison;Schwab, Kristin;Juchniewicz, Karol;Urbanik, Andrzej;Rost, Natalia S.;Viswanathan, Anand;Seifert-Held, Thomas;Stoegerer, Eva-Maria;Tomas, Marta;Rabionet, Raquel;Estivill, Xavier;Brown, Devin L.;Silliman, Scott L.;Selim, Magdy;Worrall, Bradford B.;Meschia, James F.;Montaner, Joan;Lindgren, Arne;Roquer, Jaume;Schmidt, Reinhold;Greenberg, Steven M.;Slowik, Agnieszka;Broderick, Joseph P.;Woo, Daniel;Rosand, Jonathan
既往研究APOE等位基因ε2 / ε4与脑出血（ICH）风险之间的相关性不一致，仅限于小样本量，未考虑人群分层的混杂因素，也未确定最佳应用的遗传风险模型。我们对来自7个队列的2，189例ICH病例和4，041例对照进行了大规模的遗传关联研究，使用ε2和ε4的加性模型进行了分析。随后使用随机效应模型对结果进行荟萃分析。一部分个体（322例和357例对照）有可用的全基因组数据来调整人口分层。ε2和ε4在全基因组显著性水平上与脑叶ICH相关（比值比（OR）= 1.82，95%置信区间（CI）1.50 - 2.23，p = 6.6 × 10−10和OR = 2.20，95%CI 1.85 - 2.63，p = 2.4 × 10−11）。将分析限制于明确/很可能CAA ICH，发现了更强的影响。ε4也与深部ICH风险增加相关（OR = 1.21，95% CI 1.08 - 1.36，p = 2.6 × 10−4）。风险预测评价确定的加性模型作为最好的描述APOE基因型的影响。APOE ε2和ε4是脑叶性ICH的独立危险因素，与其已知的淀粉样蛋白生物学相关性一致。此外，我们提出了APOE ε4与深部脑出血之间新关联的初步发现。最后，我们证明了这些APOE变异的加性模型是上级其他形式的遗传风险建模先前应用。
Prior studies investigating the association between APOE alleles ε2 / ε4 and risk of Intracerebral Hemorrhage (ICH) have been inconsistent, limited to small sample sizes and did not account for confounding by population stratification or determine which genetic risk model was best applied. We performed a large-scale genetic association study of 2,189 ICH cases and 4,041 controls from seven cohorts, which were analyzed using additive models for ε2 and ε4. Results were subsequently meta-analyzed using a random effects model. A proportion of the individuals (322 cases and 357 controls) had available genome-wide data to adjust for population stratification. ε2 and ε4 were associated with lobar ICH at genome-wide significance levels (Odds Ratio (OR) = 1.82, 95% Confidence Interval (CI) 1.50 – 2.23, p = 6.6 × 10−10 and OR = 2.20, 95%CI 1.85 – 2.63, p = 2.4 × 10−11 respectively). Restriction of analysis to definite / probable CAA ICH uncovered a stronger effect. ε4 was also associated with increased risk for deep ICH (OR = 1.21, 95% CI 1.08 – 1.36, p = 2.6 × 10−4). Risk prediction evaluation identified the additive model as best for describing the effect of APOE genotypes. APOE ε2 and ε4 are independent risk factors for lobar ICH, consistent with their known associations with amyloid biology. In addition, we present preliminary findings on a novel association between APOE ε4 and deep ICH. Finally, we demonstrate that an additive model for these APOE variants is superior to other forms of genetic risk modeling previously applied.
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影响因子：
3.5
作者：
Catto, AJ;McCormack, LJ;Grant, PJ
通讯作者：
Grant, PJ
影响因子：
9.9
作者：
Knudsen, KA;Rosand, J;Greenberg, SM
通讯作者：
Greenberg, SM
影响因子：
2.9
作者：
Pera, Joanna;Slowik, Agnieszka;Szczudlik, Andrzej
通讯作者：
Szczudlik, Andrzej
影响因子：
8.3
作者：
Greenberg, SM;Eng, JA;Rosand, J
通讯作者：
Rosand, J
影响因子：
--
作者：
Biffi, Alessandro;Anderson, Christopher D.;Desikan, Rahul S.;Sabuncu, Mert;Cortellini, Lynelle;Schmansky, Nick;Salat, David;Rosand, Jonathan
通讯作者：
Rosand, Jonathan