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基于家系的注意缺陷多动障碍全基因组关联扫描研究

Family-based genome-wide association scan of attention-deficit/hyperactivity disorder.

机构信息

Massachusetts General Hospital, 55 Fruit Street-Warren 705, Boston, MA 02114, USA.

出版信息

J Am Acad Child Adolesc Psychiatry. 2010 Sep;49(9):898-905.e3. doi: 10.1016/j.jaac.2010.02.014. Epub 2010 May 14.

Abstract

OBJECTIVE

Genes likely play a substantial role in the etiology of attention-deficit/hyperactivity disorder (ADHD). However, the genetic architecture of the disorder is unknown, and prior genome-wide association studies (GWAS) have not identified a genome-wide significant association. We have conducted a third, independent, multisite GWAS of DSM-IV-TR ADHD.

METHOD

Families were ascertained at Massachusetts General Hospital (MGH; N = 309 trios), Washington University at St. Louis (WASH-U; N = 272 trios), and University of California at Los Angeles (UCLA; N = 156 trios). Genotyping was conducted with the Illumina Human1M or Human1M-Duo BeadChip platforms. After applying quality control filters, association with ADHD was tested with 835,136 SNPs in 735 DSM-IV ADHD trios from 732 families.

RESULTS

Our smallest p value (6.7E-07) did not reach the threshold for genome-wide statistical significance (5.0E-08), but one of the 20 most significant associations was located in a candidate gene of interest for ADHD (SLC9A9, rs9810857, p = 6.4E-6). We also conducted gene-based tests of candidate genes identified in the literature and found additional evidence of association with SLC9A9.

CONCLUSIONS

We and our colleagues in the Psychiatric GWAS Consortium are working to pool together GWAS samples to establish the large data sets needed to follow-up on these results and to identify genes for ADHD and other disorders.

摘要

目的

基因可能在注意缺陷多动障碍(ADHD)的病因中起重要作用。然而,该疾病的遗传结构尚不清楚,先前的全基因组关联研究(GWAS)并未发现全基因组显著关联。我们进行了第三次独立的多中心 DSM-IV-TR ADHD 全基因组关联研究。

方法

在马萨诸塞州综合医院(MGH;N=309 个三核苷酸)、圣路易斯华盛顿大学(WASH-U;N=272 个三核苷酸)和加利福尼亚大学洛杉矶分校(UCLA;N=156 个三核苷酸)确定了家庭。使用 Illumina Human1M 或 Human1M-Duo BeadChip 平台进行基因分型。在应用质量控制过滤器后,用 732 个家庭的 735 个 DSM-IV ADHD 三核苷酸中的 835,136 个 SNP 测试与 ADHD 的关联。

结果

我们的最小 p 值(6.7E-07)未达到全基因组统计学显著性(5.0E-08)的阈值,但 20 个最显著关联之一位于 ADHD 的候选基因(SLC9A9,rs9810857,p=6.4E-6)。我们还对文献中确定的候选基因进行了基于基因的测试,发现了与 SLC9A9 相关的额外证据。

结论

我们和我们在精神疾病 GWAS 联盟的同事正在努力汇集 GWAS 样本,以建立需要跟进这些结果并识别 ADHD 和其他疾病基因的大型数据集。

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