Department of Medicine, University of Washington, Seattle, WA, USA.
Hum Genet. 2011 Jan;129(1):59-70. doi: 10.1007/s00439-010-0899-z. Epub 2010 Oct 21.
Performance IQ (PIQ) greater than verbal IQ (VIQ) is often observed in studies of the cognitive abilities of autistic individuals. This characteristic is correlated with social and communication impairments, key parts of the autism diagnosis. We present the first genetic analyses of IQ discrepancy (PIQ-VIQ) as an autism-related phenotype. We performed genome-wide joint linkage and segregation analyses on 287 multiplex families, using a Markov chain Monte Carlo approach. Genetic data included a genome-scan of 387 micro-satellite markers in 210 families augmented with additional markers added in a subset of families. Empirical P values were calculated for five interesting regions. Linkage analysis identified five chromosomal regions with substantial regional evidence of linkage; 10p12 [P = 0.001; genome-wide (gw) P = 0.05], 16q23 (P = .015; gw P = 0.53), 2p21 (P = 0.03, gw P = 0.78), 6q25 (P = 0.047, gw P = 0.91) and 15q23-25 (P = 0.053, gw P = 0.93). The location of the chromosome 10 linkage signal coincides with a region noted in a much earlier genome-scan for autism, and the chromosome 16 signal coincides exactly with a linkage signal for non-word repetition in specific language impairment. This study provides strong evidence for a QTL influencing IQ discrepancy in families with autistic individuals on chromosome 10, and suggestive evidence for a QTL on chromosome 16. The location of the chromosome 16 signal suggests a candidate gene, CDH13, a T-cadherin expressed in the brain, which has been implicated in previous SNP studies of autism and ADHD.
在对自闭症个体认知能力的研究中，常观察到表现智商（PIQ）高于言语智商（VIQ）。这一特征与社交和沟通障碍相关，后者是自闭症诊断的关键部分。我们首次对智商差异（PIQ-VIQ）作为自闭症相关表型进行了遗传分析。我们使用马尔可夫链蒙特卡罗方法对 287 个多基因家族进行了全基因组联合连锁和分离分析。遗传数据包括对 210 个家庭的 387 个微卫星标记进行的基因组扫描，以及在一部分家庭中添加的额外标记的补充数据。对五个有趣区域计算了经验 P 值。连锁分析确定了五个具有大量区域连锁证据的染色体区域；10p12[P=0.001；全基因组（gw）P=0.05]，16q23（P=0.015；gw P=0.53），2p21（P=0.03，gw P=0.78），6q25（P=0.047，gw P=0.91）和 15q23-25（P=0.053，gw P=0.93）。染色体 10 连锁信号的位置与早期自闭症全基因组扫描中注意到的区域相吻合，而染色体 16 信号与特定语言障碍中非词重复的连锁信号完全吻合。这项研究为在自闭症个体的家族中影响智商差异的 QTL 提供了强有力的证据，而染色体 16 上的 QTL 则提供了有希望的证据。染色体 16 信号的位置提示候选基因 CDH13，这是一种在大脑中表达的 T-钙粘蛋白，它在自闭症和 ADHD 的先前 SNP 研究中已被涉及。
