Genetic loci associated with Alzheimer's disease and cerebrospinal fluid biomarkers in a Finnish case-control cohort.
Genetic loci associated with Alzheimer's disease and cerebrospinal fluid biomarkers in a Finnish case-control cohort.
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与阿尔茨海默氏病和脑脊液生物标志物相关的遗传基因座在芬兰病例控制队列中。
DOI：
10.1371/journal.pone.0059676
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Hiltunen M
中科院分区：
文献类型：
--
作者：
Elias-Sonnenschein LS;Helisalmi S;Natunen T;Hall A;Paajanen T;Herukka SK;Laitinen M;Remes AM;Koivisto AM;Mattila KM;Lehtimäki T;Verhey FR;Visser PJ;Soininen H;Hiltunen M
为了了解阿尔茨海默病（AD）风险基因之间的关系及其对AD生物标志物的影响，我们检查了芬兰队列中AD与来自顶级AlzGene基因座、全基因组关联研究（GWAS）和候选基因研究的单核苷酸多态性（SNP）的关联;并检测这些SNPs与AD标志物Aβ1-42、脑脊液中总tau（t-tau）和磷酸化tau（p-tau）的相关性。我们使用逻辑回归分析在我们的队列中检测了25个SNP与临床AD的遗传关联，该队列包括890名AD患者和701名年龄匹配的健康对照。对于与生物标志物的相关性研究，我们使用混合模型在222名具有可用CSF的AD患者的子集中测试了36个SNP。统计分析根据年龄、性别和APOE状态进行调整。应用了多次测试的错误发现率。所有参与者都来自芬兰的学术医院和研究机构。 APOE-ε4、CLU rs 11136000和MS 4A 4A rs 2304933与Aβ1-42显著降低相关（校正p<0.05）。在未校正的p<0.05时，PPP 3R 1 rs 1868402和MAPT rs 2435211与t-tau增加相关;而SORL 1 rs73595277和MAPT rs 16940758与p-tau增加相关。在校正APOE-ε4后，仅TOMM 40 rs 2075650显示与临床AD相关（p = 0.007），但在多重检验校正后则无相关性（p>0.05）。 我们提供的证据表明，在GWAS中已确定与AD相关的APOE-ε4、CLU和MS 4A 4A也显著降低了AD患者的CSF Aβ1-42。其他AlzGene和GWAS基因座均未显示对CSF tau的显著影响。其他SNP对CSF生物标志物和临床AD诊断的影响未达到统计学显著性。我们的研究结果表明，APOE-ε4、CLU和MS 4A 4A影响AD风险和CSF Aβ1-42。
To understand the relation between risk genes for Alzheimer’s disease (AD) and their influence on biomarkers for AD, we examined the association of AD in the Finnish cohort with single nucleotide polymorphisms (SNPs) from top AlzGene loci, genome-wide association studies (GWAS), and candidate gene studies; and tested the correlation between these SNPs and AD markers Aβ1–42, total tau (t-tau), and phosphorylated tau (p-tau) in cerebrospinal fluid (CSF). We tested 25 SNPs for genetic association with clinical AD in our cohort comprised of 890 AD patients and 701-age matched healthy controls using logistic regression. For the correlational study with biomarkers, we tested 36 SNPs in a subset of 222 AD patients with available CSF using mixed models. Statistical analyses were adjusted for age, gender and APOE status. False discovery rate for multiple testing was applied. All participants were from academic hospital and research institutions in Finland. APOE-ε4, CLU rs11136000, and MS4A4A rs2304933 correlated with significantly decreased Aβ1–42 (corrected p<0.05). At an uncorrected p<0.05, PPP3R1 rs1868402 and MAPT rs2435211 were related with increased t-tau; while SORL1 rs73595277 and MAPT rs16940758, with increased p-tau. Only TOMM40 rs2075650 showed association with clinical AD after adjusting for APOE-ε4 (p = 0.007), but not after multiple test correction (p>0.05). We provide evidence that APOE-ε4, CLU and MS4A4A, which have been identified in GWAS to be associated with AD, also significantly reduced CSF Aβ1–42 in AD. None of the other AlzGene and GWAS loci showed significant effects on CSF tau. The effects of other SNPs on CSF biomarkers and clinical AD diagnosis did not reach statistical significance. Our findings suggest that APOE-ε4, CLU and MS4A4A influence both AD risk and CSF Aβ1–42.
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DOI：
10.1016/s0140-6736(20)32205-4
发表时间：
2021-04-24
期刊：
Lancet (London, England)
影响因子：
--
作者：
Scheltens P;De Strooper B;Kivipelto M;Holstege H;Chételat G;Teunissen CE;Cummings J;van der Flier WM
通讯作者：
van der Flier WM
DOI：
10.1073/pnas.0801227105
发表时间：
2008-06-10
影响因子：
11.1
作者：
Kauwe, John S. K.;Cruchaga, Carlos;Goate, Alison M.
通讯作者：
Goate, Alison M.
影响因子：
4.2
作者：
Lambert, Jean-Charles;Zelenika, Diana;Amouyel, Philippe
通讯作者：
Amouyel, Philippe
影响因子：
5.3
作者：
Johansson, A;Katzov, H;Prince, JA
通讯作者：
Prince, JA
DOI：
10.1002/ajmg.b.32094
发表时间：
2012-10
影响因子：
2.8
作者：
Bekris, Lynn M.;Millard, Steve;Lutz, Franziska;Li, Gail;Galasko, Doug R.;Farlow, Martin R.;Quinn, Joseph F.;Kaye, Jeffrey A.;Leverenz, James B.;Tsuang, Debby W.;Yu, Chang-En;Peskind, Elaine R.
通讯作者：
Peskind, Elaine R.