Department of Epidemiology and International Health, University of Alabama at Birmingham, Birmingham, AL, USA.
Schizophr Bull. 2013 Mar;39(2):464-71. doi: 10.1093/schbul/sbr161. Epub 2012 Jan 10.
Various measures of neurocognitive function show mean differences among individuals with schizophrenia (SZ), their relatives, and population controls. We use eigenvector transformations that maximize heritability of multiple neurocognitive measures, namely principal components of heritability (PCH), and evaluate how they distribute in SZ families and controls.
African-Americans with SZ or schizoaffective disorder (SZA) (n = 514), their relatives (n = 1092), and adult controls (n = 300) completed diagnostic interviews and computerized neurocognitive tests. PCH were estimated from 9 neurocognitive domains. Three PCH, PCH1-PCH3, were modeled to determine if status (SZ, relative, and control), other psychiatric covariates, and education were significant predictors of mean values. A small-scale linkage analysis was also conducted in a subset of the sample.
PCH1, PCH2, and PCH3 account for 72% of the genetic variance. PCH1 represents 8 of 9 neurocognitive domains, is most highly correlated with spatial processing and emotion recognition, and has unadjusted heritability of 68%. The means for PCH1 differ significantly among SZ, their relatives, and controls. PCH2, orthogonal to PCH1, is most closely correlated with working memory and has an unadjusted heritability of 45%. Mean PCH2 is different only between SZ families and controls. PCH3 apparently represents a heritable component of neurocognition similar across the 3 diagnostic groups. No significant linkage evidence to PCH1-PCH3 or individual neurocognitive measures was discovered.
PCH1 is highly heritable and genetically correlated with SZ. It should prove useful in future genetic analyses. Mean PCH2 differentiates SZ families and controls but not SZ and unaffected family members.
各种神经认知功能的衡量标准显示出精神分裂症（SZ）患者、他们的亲属和普通人群之间存在平均差异。我们使用最大程度地提高多个神经认知测量遗传性的特征向量转换，即遗传主成分（PCH），并评估它们在 SZ 家庭和对照组中的分布情况。
514 名患有 SZ 或分裂情感障碍（SZA）的非裔美国人、他们的亲属（1092 名）和成年对照组（300 名）完成了诊断访谈和计算机化神经认知测试。从 9 个神经认知领域估计了 PCH。对 3 个 PCH（PCH1-PCH3）进行建模，以确定状态（SZ、亲属和对照）、其他精神科协变量和教育是否是平均值的重要预测因素。在样本的一个子集中还进行了小规模的连锁分析。
PCH1、PCH2 和 PCH3 占遗传方差的 72%。PCH1 代表 9 个神经认知领域中的 8 个，与空间处理和情绪识别相关性最高，未经调整的遗传率为 68%。PCH1 的平均值在 SZ、他们的亲属和对照组之间有显著差异。PCH2 与 PCH1 正交，与工作记忆最密切相关，未经调整的遗传率为 45%。仅在 SZ 家庭和对照组之间存在 PCH2 的平均值差异。PCH3 显然代表了 3 个诊断组之间相似的可遗传的神经认知成分。未发现 PCH1-PCH3 或单个神经认知测量值的显著连锁证据。
PCH1 具有高度遗传性，与 SZ 存在遗传相关性。它应该在未来的遗传分析中证明是有用的。平均 PCH2 可区分 SZ 家庭和对照组，但不能区分 SZ 和未受影响的家庭成员。
