Schizophrenia genetic variants are not associated with intelligence.
Schizophrenia genetic variants are not associated with intelligence.
复制标题
DOI：
10.1017/s0033291713000196
复制
发表时间：
2013-12
影响因子：
6.9
通讯作者：
Kahn RS
中科院分区：
文献类型：
--
作者：
van Scheltinga AF;Bakker SC;van Haren NE;Derks EM;Buizer-Voskamp JE;Cahn W;Ripke S;Psychiatric Genome-Wide Association Study (GWAS) Consortium;Ophoff RA;Kahn RS
精神分裂症除了（发病前）认知能力下降外，还与发病前智力（IQ）较低有关。精神分裂症和智商都是高度遗传的特征。因此，我们假设与精神分裂症相关的遗传变异，包括拷贝数变异（CNVs）和多基因精神分裂症（风险）评分（PSS），可能会影响智力。采用韦氏成人智力量表（WAIS）评估智商。使用QuantiSNP和PennCNV算法从单核苷酸多态性（SNP）数据确定CNV。对于PSS，在精神病全基因组关联研究（GWAS）联盟收集的样本（8690名精神分裂症患者和11831名对照）中计算全基因组SNP数据的比值比。这些被用来计算个人的PSS在我们的独立样本的350名精神分裂症患者和322名健康对照。虽然与对照组相比，精神分裂症患者中有更多的基因被缺失破坏（p=0.009），但CNV测量对智商没有影响。在整个样本中，PSS与疾病状态（R2=0.055，p=2.1×10−7）和智商（R2=0.018，p=0.0008）相关，但在校正疾病状态后，对智商的影响消失了。我们的数据表明，罕见和常见的精神分裂症相关变异不能解释健康受试者或精神分裂症患者的智商变化。因此，精神分裂症患者的智商降低可能是继发于与精神分裂症风险相关的其他过程。
Schizophrenia is associated with lower pre-morbid intelligence (IQ) in addition to (pre-morbid) cognitive decline. Both schizophrenia and IQ are highly heritable traits. Therefore, we hypothesized that genetic variants associated with schizophrenia, including copy number variants (CNVs) and a polygenic schizophrenia (risk) score (PSS), may influence intelligence. IQ was estimated with the Wechsler Adult Intelligence Scale (WAIS). CNVs were determined from single nucleotide polymorphism (SNP) data using the QuantiSNP and PennCNV algorithms. For the PSS, odds ratios for genome-wide SNP data were calculated in a sample collected by the Psychiatric Genome-Wide Association Study (GWAS) Consortium (8690 schizophrenia patients and 11 831 controls). These were used to calculate individual PSSs in our independent sample of 350 schizophrenia patients and 322 healthy controls. Although significantly more genes were disrupted by deletions in schizophrenia patients compared to controls (p=0.009), there was no effect of CNV measures on IQ. The PSS was associated with disease status (R2=0.055, p=2.1×10−7) and with IQ in the entire sample (R2=0.018, p=0.0008) but the effect on IQ disappeared after correction for disease status. Our data suggest that rare and common schizophrenia-associated variants do not explain the variation in IQ in healthy subjects or in schizophrenia patients. Thus, reductions in IQ in schizophrenia patients may be secondary to other processes related to schizophrenia risk.