Brandl E J, Tiwari A K, Zai C C, Nurmi E L, Chowdhury N I, Arenovich T, Sanches M, Goncalves V F, Shen J J, Lieberman J A, Meltzer H Y, Kennedy J L, Müller D J
Pharmacogenetics Research Clinic, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada.
Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, Berlin, Germany.
Pharmacogenomics J. 2016 Aug;16(4):352-6. doi: 10.1038/tpj.2015.59. Epub 2015 Sep 1.
Antipsychotic-induced weight gain (AIWG) is a common side effect with a high genetic contribution. We reanalyzed genome-wide association study (GWAS) data from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) selecting a refined subset of patients most suitable for AIWG studies. The final GWAS was conducted in N=189 individuals. The top polymorphisms were analyzed in a second cohort of N=86 patients. None of the single-nucleotide polymorphisms was significant at the genome-wide threshold of 5x10(-8). We observed interesting trends for rs9346455 (P=6.49x10(-6)) upstream of OGFRL1, the intergenic variants rs7336345 (P=1.31 × 10(-5)) and rs1012650 (P=1.47 × 10(-5)), and rs1059778 (P=1.49x10(-5)) in IBA57. In the second cohort, rs9346455 showed significant association with AIWG (P=0.005). The combined meta-analysis P-value for rs9346455 was 1.09 × 10(-7). Our reanalysis of the CATIE GWAS data revealed interesting new variants associated with AIWG. As the functional relevance of these polymorphisms is yet to be determined, further studies are needed.The Pharmacogenomics Journal advance online publication, 1 September 2015; doi:10.1038/tpj.2015.59.
抗精神病药物所致体重增加（AIWG）是一种常见的副作用，且具有较高的遗传因素。我们重新分析了干预有效性临床抗精神病药物试验（CATIE）的全基因组关联研究（GWAS）数据，选择了最适合AIWG研究的患者精细子集。最终的GWAS在N = 189名个体中进行。在另一组N = 86名患者中对顶级多态性进行了分析。在全基因组阈值5×10⁻⁸下，没有单核苷酸多态性是显著的。我们观察到OGFRL1上游的rs9346455（P = 6.49×10⁻⁶）、基因间变体rs7336345（P = 1.31×10⁻⁵）和rs1012650（P = 1.47×10⁻⁵）以及IBA57中的rs1059778（P = 1.49×10⁻⁵）呈现出有趣的趋势。在第二个队列中，rs9346455与AIWG显示出显著关联（P = 0.005）。rs9346455的合并荟萃分析P值为1.09×10⁻⁷。我们对CATIE GWAS数据的重新分析揭示了与AIWG相关的有趣新变体。由于这些多态性的功能相关性尚未确定，因此需要进一步研究。《药物基因组学杂志》在线优先发表，2015年9月1日；doi:10.1038/tpj.2015.59 。
