Supplementary Material for: Association of Dystrobrevin-Binding Protein 1 Polymorphisms with Sustained Attention and Set-Shifting in Schizophrenia Patients

<i>Background:</i> Despite extensive research in the past decades, the influence of genetics on cognitive functions in schizophrenia remains unclear. Dystrobrevin-binding protein 1 <i>(DTNBP1)</i> is one of the most promising candidate genes in schizophrenia. An association of <i>DTNBP1</i> with cognitive dysfunction, particularly memory impairment, has been reported in a number of studies. However, the results remain inconsistent. The aim of this study was to measure the association between <i>DTNBP1</i> polymorphisms and cognitive domains in a well-characterized sample. <i>Methods:</i> Ninety-one clinically stable schizophrenia outpatients underwent a battery of cognitive tests. Six single nucleotide polymorphisms (SNPs) of <i>DTNBP1</i> were genotyped in all participants. Statistical and multivariate analyses were performed. <i>Results:</i> Factor analysis revealed 4 factors corresponding to distinct cognitive domains, namely sustained attention, set-shifting, executive functioning, and memory. We found a significant association of the rs909706 polymorphism with attention (p = 0.030) and a nonsignificant trend for set-shifting (p = 0.060). The other SNPs and haplotypes were not associated with cognitive function. <i>Discussion:</i>Replication of this finding in a larger sample is needed in order to confirm the importance of this particular polymorphism in the genetics of schizophrenia, particularly the distinct cognitive domains. In conclusion, the present study supports the involvement of <i>DTNBP1 </i>in the regulation of cognitive processes and demonstrates association in particular with sustained attention and set-shifting in schizophrenia patients.

背景：尽管数十年来开展了大量研究，遗传学因素对精神分裂症患者认知功能的影响仍未明确。肌营养不良蛋白结合蛋白1（Dystrobrevin-binding protein 1，DTNBP1）是精神分裂症最具潜力的候选基因之一。多项研究已报道DTNBP1与认知功能障碍，尤其是记忆损害存在关联，但相关研究结果始终不一致。本研究旨在通过特征明确的研究样本，分析DTNBP1基因多态性与各认知域之间的关联。
方法：本研究纳入91名病情稳定的精神分裂症门诊患者，对其实施一套认知测试组合。对所有受试者的DTNBP1基因的6个单核苷酸多态性（Single Nucleotide Polymorphisms，SNPs）进行基因分型，并开展统计学与多变量分析。
结果：因子分析提取出4个对应不同认知域的因子，分别为持续性注意力、任务转换、执行功能与记忆功能。本研究发现rs909706多态性与注意力存在显著关联（p=0.030），且与任务转换存在接近显著的趋势（p=0.060）。其余SNP位点及单体型均未发现与认知功能存在关联。
讨论：未来需要在更大样本量的研究中重复本研究结果，以明确该特定多态性在精神分裂症遗传学，尤其是其对特定认知域影响中的重要性。综上，本研究支持DTNBP1参与认知过程的调控，并证实其与精神分裂症患者的持续性注意力及任务转换功能存在特定关联。