Division of Psychology and Language Sciences, University College London, UK.
J Child Psychol Psychiatry. 2010 Jul;51(7):780-8. doi: 10.1111/j.1469-7610.2010.02236.x. Epub 2010 Mar 25.
Quantitative genetic data from our group indicates that antisocial behaviour (AB) is strongly heritable when coupled with psychopathic, callous-unemotional (CU) personality traits. We have also demonstrated that the genetic influences for AB and CU overlap considerably. We conducted a genome-wide association scan that capitalises on these findings in an attempt to identify quantitative trait loci (QTLs) that may increase risk for psychopathic tendencies (AB+/CU+).
Teacher ratings at age 7 were used to screen 8374 twins with available DNA samples for individuals that were high vs. low on both AB and CU. In Stage 1, we screened for allele frequency differences in 642,432 autosomal single-nucleotide polymorphisms (SNPs) using the Affymetrix 6.0 GeneChip with pooled DNA for high-scoring (AB+/CU+) versus low-scoring children (N = approximately 300/group). In Stage 2, we tested the 3000 most strongly associated SNPs from Stage 1 for association in the same direction in a second sample of high- versus low-scoring children from the same twin study (18% co-twins).
Using allele frequencies estimated from pooled DNA, we found suggestive evidence for enrichment of association in the second stage of our two-stage genome-wide association design and focus on reporting the 30 top-ranking SNPs nominally associated with psychopathic tendencies. These SNPs include neurodevelopmental genes such as ROBO2.
Although none of the SNPs reached genome-wide statistical significance we have generated a list of SNPs that are potentially associated with psychopathic tendencies, which we believe warrant verification and replication in large independent and clinical samples.
我们小组的定量遗传学数据表明，当反社会行为（AB）与精神病态、冷酷无情（CU）人格特征相结合时，其具有很强的遗传性。我们还证明了 AB 和 CU 的遗传影响有很大的重叠。我们进行了全基因组关联扫描，利用这些发现试图确定可能增加精神病态倾向（AB+/CU+）风险的数量性状基因座（QTL）。
使用 7 岁时教师的评分，对 8374 名具有可用 DNA 样本的双胞胎进行筛选，以确定在 AB 和 CU 两个方面都得分高和得分低的个体。在第一阶段，我们使用 Affymetrix 6.0 GeneChip 对 pooled DNA 进行了 642,432 个常染色体单核苷酸多态性（SNP）的等位基因频率差异筛查，用于高分（AB+/CU+）与低分（N=约 300/组）儿童的比较。在第二阶段，我们在同一双胞胎研究的高得分与低得分儿童的第二个样本中，对第一阶段的 3000 个最强烈关联的 SNP 进行了相同方向的关联测试（18%的同卵双胞胎）。
使用从 pooled DNA 中估计的等位基因频率，我们在我们的两阶段全基因组关联设计的第二阶段发现了关联富集的证据，并集中报告了 30 个名义上与精神病态倾向相关的排名最高的 SNP。这些 SNP 包括神经发育基因，如 ROBO2。
尽管没有一个 SNP 达到全基因组统计学意义，但我们已经生成了一份可能与精神病态倾向相关的 SNP 列表，我们认为这些 SNP 需要在大的独立和临床样本中进行验证和复制。
