Division of Biostatistics, Washington University School of Medicine, St. Louis, MO, USA.
BMC Genet. 2005 Dec 30;6 Suppl 1(Suppl 1):S94. doi: 10.1186/1471-2156-6-S1-S94.
This study, part of the Genetic Analysis Workshop 14 (GAW14), explored real Collaborative Study on the Genetics of Alcoholism data for linkage and association mapping between genetic polymorphisms (microsatellite and single-nucleotide polymorphisms (SNPs)) and beta (16.5-20 Hz) oscillations of the brain rhythms (ecb21). The ecb21 phenotype underwent the statistical adjustments for the age of participants, and for attaining a normal distribution. A total of 1,000 subjects' available phenotypes were included in linkage analysis with microsatellite markers. Linkage analysis was performed only for chromosome 4 where a quantitative trait locus with 5.01 LOD score had been previously reported. Previous findings related this location with the gamma-aminobutyric acid type A (GABAA) receptor. At the same location, our analysis showed a LOD score of 2.2. This decrease in the LOD score is the result of a drastic reduction (one-third) of the available GAW14 phenotypic data. We performed SNP and haplotype association analyses with the same phenotypic data under the linkage peak region on chromosome 4. Seven Affymetrix and two Illumina SNPs showed significant associations with ecb21 phenotype. A haplotype, a combination of SNPs TSC0044171 and TSC0551006 (the latter almost under the region of GABAA genes), showed a significant association with ecb21 (p = 0.015) and a relatively high frequency in the sample studied. Our results affirmed that the GABA region has potential of harboring genes that contribute quantitatively to the beta oscillation of the brain rhythms. The inclusion of the remaining 614 subjects, which in the GAW14 had missing data for the ecb21, can improve the strength of the associations as they have already shown that they contribute quite important information in the linkage analysis.
本研究是遗传分析工作坊 14(GAW14)的一部分,旨在探索酒精中毒遗传学的真实协作研究数据,以进行遗传多态性(微卫星和单核苷酸多态性(SNP))与大脑节律β(16.5-20Hz)振荡之间的连锁和关联映射。ecb21 表型经过了对参与者年龄的统计调整,并达到了正态分布。共有 1000 名受试者的可用表型被纳入微卫星标记的连锁分析。仅对先前报道的具有 5.01 LOD 评分的数量性状位点的染色体 4 进行连锁分析。先前的研究结果将该位置与γ-氨基丁酸 A 型(GABAA)受体相关联。在同一位置,我们的分析显示 LOD 评分为 2.2。LOD 评分的降低是由于 GAW14 表型数据可用数量的急剧减少(三分之一)所致。我们在染色体 4 上的连锁峰区域对相同的表型数据进行了 SNP 和单倍型关联分析。7 个 Affymetrix 和 2 个 Illumina SNP 与 ecb21 表型显示出显著关联。一个单倍型,即 SNP TSC0044171 和 TSC0551006 的组合(后者几乎在 GABAA 基因区域),与 ecb21 表现出显著关联(p=0.015),并且在研究样本中具有相对较高的频率。我们的研究结果证实,GABA 区域有可能存在对大脑节律β振荡有定量贡献的基因。纳入 GAW14 中 ecb21 缺失数据的其余 614 名受试者可以提高关联的强度,因为他们已经表明他们在连锁分析中提供了相当重要的信息。