荷兰乌得勒支大学医学中心Jacob A. S. Vorstman研究组取得一项新突破。他们发现利用常见遗传变异可以检查22q11.2缺失综合征（22q11DS）的典型基因表达以及预测发病风险。相关论文于2020年11月9日发表在《自然-医学》杂志上。

在962名22q11DS患者中，研究人员探究了精神分裂症和与精神分裂症相关早期征兆表型之间的共同遗传基础：精神病的亚阈值症状、低基线智力功能和认知能力下降。研究人员将这些表型与两个针对精神分裂症和智力的多基因评分相关联，并评估了它们在22q11DS中用于个体风险预测的价值。多基因评分不仅分别与精神分裂症和基线智商（IQ）相关，而且精神分裂症多基因评分还与认知（言语智商）下降显著相关，并且还与亚阈值精神病相关。

此外，在比较精神分裂症和IQ多基因评分分布的尾部时，在33％的22q11DS患者中有9％的人患有患有精神分裂症，在63％的22q11DS患者中有24％的患者具有智力障碍。

总体而言，这些数据显示了精神分裂症和精神分裂症相关表型之间的共遗传基础，也突出了多基因评分在具有高度但不完全相同遗传变异个体之间进行风险分层的应用潜能。 

研究人员表示，22q11.2缺失综合征增加了20–25％的精神分裂症发病风险。

附：英文原文

Title: Using common genetic variation to examine phenotypic expression and risk prediction in 22q11.2 deletion syndrome

Author: Robert W. Davies, Ania M. Fiksinski, Elemi J. Breetvelt, Nigel M. Williams, Stephen R. Hooper, Thomas Monfeuga, Anne S. Bassett, Michael J. Owen, Raquel E. Gur, Bernice E. Morrow, Donna M. McDonald-McGinn, Ann Swillen, Eva W. C. Chow, Marianne van den Bree, Beverly S. Emanuel, Joris R. Vermeesch, Therese van Amelsvoort, Celso Arango, Marco Armando, Linda E. Campbell, Joseph F. Cubells, Stephan Eliez, Sixto Garcia-Minaur, Doron Gothelf, Wendy R. Kates, Kieran C. Murphy, Clodagh M. Murphy, Declan G. Murphy, Nicole Philip, Gabriela M. Repetto, Vandana Shashi, Tony J. Simon, Damin Heine Suer, Stefano Vicari, Stephen W. Scherer, Carrie E. Bearden, Jacob A. S. Vorstman

Issue&Volume: 2020-11-09

Abstract: The 22q11.2 deletion syndrome (22q11DS) is associated with a 20–25% risk of schizophrenia. In a cohort of 962 individuals with 22q11DS, we examined the shared genetic basis between schizophrenia and schizophrenia-related early trajectory phenotypes: sub-threshold symptoms of psychosis, low baseline intellectual functioning and cognitive decline. We studied the association of these phenotypes with two polygenic scores, derived for schizophrenia and intelligence, and evaluated their use for individual risk prediction in 22q11DS. Polygenic scores were not only associated with schizophrenia and baseline intelligence quotient (IQ), respectively, but schizophrenia polygenic score was also significantly associated with cognitive (verbal IQ) decline and nominally associated with sub-threshold psychosis. Furthermore, in comparing the tail-end deciles of the schizophrenia and IQ polygenic score distributions, 33% versus 9% of individuals with 22q11DS had schizophrenia, and 63% versus 24% of individuals had intellectual disability. Collectively, these data show a shared genetic basis for schizophrenia and schizophrenia-related phenotypes and also highlight the future potential of polygenic scores for risk stratification among individuals with highly, but incompletely, penetrant genetic variants.

DOI: 10.1038/s41591-020-1103-1

Source: https://www.nature.com/articles/s41591-020-1103-1