Ovenden Ellen S, Drögemöller Britt I, van der Merwe Lize, Chiliza Bonginkosi, Asmal Laila, Emsley Robin A, Warnich Louise
Department of Genetics, Stellenbosch University, Stellenbosch, South Africa.
Department of Psychiatry, Stellenbosch University, Tygerberg, South Africa.
Pharmacogenomics. 2017 Jan;18(2):105-120. doi: 10.2217/pgs-2016-0108. Epub 2016 Dec 19.
Noncoding variation has demonstrated regulatory effects on disease treatment outcomes. This study investigated the potential functionality of previously implicated noncoding variants on schizophrenia treatment response.
MATERIALS & METHODS: Predicted regulatory potential of variation identified from antipsychotic response genome-wide association studies was determined. Prioritized variants were assessed for association(s) with treatment outcomes in a South African first episode schizophrenia cohort (n = 103).
Bioinformatic and association results implicated a relationship between regulatory variants, expression of MANBA, COL9A2 and NFKB1, and treatment response. Three SNPs were associated with poor outcomes (rs230493: p = 1.88 × 10; rs3774959: p = 1.75 × 10; and rs230504: p = 1.48 × 10).
This study has thoroughly investigated previous GWAS to pinpoint variants that may play a causal role in poor schizophrenia treatment outcomes, and provides potential candidate genes for further study in the field of antipsychotic response.
非编码变异已被证明对疾病治疗结果具有调节作用。本研究调查了先前涉及的非编码变异对精神分裂症治疗反应的潜在功能。
确定了从抗精神病药物反应全基因组关联研究中鉴定出的变异的预测调节潜力。在一个南非首发精神分裂症队列（n = 103）中，对优先排序的变异与治疗结果的关联进行了评估。
生物信息学和关联结果表明调节变异、MANBA、COL9A2和NFKB1的表达与治疗反应之间存在关联。三个单核苷酸多态性与不良结果相关（rs230493：p = 1.88 × 10；rs3774959：p = 1.75 × 10；以及rs230504：p = 1.48 × 10）。
本研究全面调查了先前的全基因组关联研究，以确定可能在精神分裂症治疗不良结果中起因果作用的变异，并为抗精神病药物反应领域的进一步研究提供了潜在的候选基因。
