Center for Biomedical Informatics, Harvard Medical School, Boston, MA 02115, USA.
Transl Psychiatry. 2011 Dec 13;1(12):e63. doi: 10.1038/tp.2011.62.
The role of the immune system in neuropsychiatric diseases, including autism spectrum disorder (ASD), has long been hypothesized. This hypothesis has mainly been supported by family cohort studies and the immunological abnormalities found in ASD patients, but had limited findings in genetic association testing. Two cross-disorder genetic association tests were performed on the genome-wide data sets of ASD and six autoimmune disorders. In the polygenic score test, we examined whether ASD risk alleles with low effect sizes work collectively in specific autoimmune disorders and show significant association statistics. In the genetic variation score test, we tested whether allele-specific associations between ASD and autoimmune disorders can be found using nominally significant single-nucleotide polymorphisms. In both tests, we found that ASD is probabilistically linked to ankylosing spondylitis (AS) and multiple sclerosis (MS). Association coefficients showed that ASD and AS were positively associated, meaning that autism susceptibility alleles may have a similar collective effect in AS. The association coefficients were negative between ASD and MS. Significant associations between ASD and two autoimmune disorders were identified. This genetic association supports the idea that specific immunological abnormalities may underlie the etiology of autism, at least in a number of cases.
免疫系统在神经精神疾病中的作用，包括自闭症谱系障碍（ASD），长期以来一直被假设。这一假设主要得到了家族队列研究和 ASD 患者免疫异常的支持，但在遗传关联测试中发现的证据有限。对 ASD 和六种自身免疫性疾病的全基因组数据集进行了两项跨疾病遗传关联测试。在多基因评分测试中，我们检查了 ASD 风险等位基因的低效应大小是否在特定的自身免疫性疾病中集体作用，并显示出显著的关联统计数据。在遗传变异评分测试中，我们使用名义上显著的单核苷酸多态性测试了 ASD 和自身免疫性疾病之间的等位基因特异性关联是否可以找到。在这两种测试中，我们发现 ASD 与强直性脊柱炎（AS）和多发性硬化症（MS）有概率上的关联。关联系数表明，ASD 和 AS 呈正相关，这意味着自闭症易感性等位基因可能在 AS 中具有类似的集体效应。ASD 和 MS 之间的关联系数为负。ASD 与两种自身免疫性疾病之间存在显著关联。这种遗传关联支持了这样一种观点，即特定的免疫异常可能是自闭症发病机制的基础，至少在许多情况下是这样。
