位于10号染色体上的阿尔茨海默病易感基因座。

Susceptibility locus for Alzheimer's disease on chromosome 10.

作者信息

Myers A, Holmans P, Marshall H, Kwon J, Meyer D, Ramic D, Shears S, Booth J, DeVrieze F W, Crook R, Hamshere M, Abraham R, Tunstall N, Rice F, Carty S, Lillystone S, Kehoe P, Rudrasingham V, Jones L, Lovestone S, Perez-Tur J, Williams J, Owen M J, Hardy J, Goate A M

机构信息

Department of Psychiatry, Washington University School of Medicine, 660 S. Euclid, St. Louis, MO 63110, USA.

出版信息

Science. 2000 Dec 22;290(5500):2304-5. doi: 10.1126/science.290.5500.2304.

DOI:10.1126/science.290.5500.2304

PMID:11125144

Abstract

The apolipoprotein E (APOE) gene is the only genetic risk factor that has so far been linked to risk for late-onset Alzheimer's disease (LOAD). However, 50 percent of Alzheimer's disease cases do not carry an APOE4 allele, suggesting that other risk factors must exist. We performed a two-stage genome-wide screen in sibling pairs with LOAD to detect other susceptibility loci. Here we report evidence for an Alzheimer's disease locus on chromosome 10. Our stage one multipoint lod score (logarithm of the odds ratio for linkage/no linkage) of 2.48 (266 sibling pairs) increased to 3.83 in stage 2 (429 sibling pairs) close to D10S1225 (79 centimorgans). This locus modifies risk for Alzheimer's disease independent of APOE genotype.

摘要

载脂蛋白E（APOE）基因是目前唯一与晚发型阿尔茨海默病（LOAD）风险相关的遗传风险因素。然而，50%的阿尔茨海默病病例并不携带APOE4等位基因，这表明必定存在其他风险因素。我们对患有LOAD的同胞对进行了两阶段全基因组筛查，以检测其他易感基因座。在此我们报告了10号染色体上存在阿尔茨海默病基因座的证据。我们第一阶段在266对同胞对中的多点连锁对数评分（连锁/非连锁优势比的对数）为2.48，在第二阶段（429对同胞对）靠近D10S1225（79厘摩）处增加到了3.83。该基因座独立于APOE基因型改变阿尔茨海默病风险。