Molecular psychiatry · 2020

Genetic contributors to risk of schizophrenia in the presence of a 22q11.2 deletion.

СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен

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Cleynen Isabelle, Engchuan Worrawat, Hestand Matthew S, Heung Tracy, Holleman Aaron M, Johnston H Richard, Monfeuga Thomas, McDonald-McGinn Donna M, Gur Raquel E, Morrow Bernice E, Swillen Ann, Vorstman Jacob A S, Bearden Carrie E, Chow Eva W C, van den Bree Marianne, Emanuel Beverly S, Vermeesch Joris R, Warren Stephen T, Owen Michael J, Chopra Pankaj, Cutler David J, Duncan Richard, Kotlar Alex V, Mulle Jennifer G, Voss Anna J, Zwick Michael E, Diacou Alexander, Golden Aaron, Guo Tingwei, Lin Jhih-Rong, Wang Tao, Zhang Zhengdong, Zhao Yingjie, Marshall Christian, Merico Daniele, Jin Andrea, Lilley Brenna, Salmons Harold I, Tran Oanh, Holmans Peter, Pardinas Antonio, Walters James T R, Demaerel Wolfram, Boot Erik, Butcher Nancy J, Costain Gregory A, Lowther Chelsea, Evers Rens, van Amelsvoort Therese A M J, van Duin Esther, Vingerhoets Claudia, Breckpot Jeroen, Devriendt Koen, Vergaelen Elfi, Vogels Annick, Crowley T Blaine, McGinn Daniel E, Moss Edward M, Sharkus Robert J, Unolt Marta, Zackai Elaine H, Calkins Monica E, Gallagher Robert S, Gur Ruben C, Tang Sunny X, Fritsch Rosemarie, Ornstein Claudia, Repetto Gabriela M, Breetvelt Elemi, Duijff Sasja N, Fiksinski Ania, Moss Hayley, Niarchou Maria, Murphy Kieran C, Prasad Sarah E, Daly Eileen M, Gudbrandsen Maria, Murphy Clodagh M, Murphy Declan G, Buzzanca Antonio, Fabio Fabio Di, Digilio Maria C, Pontillo Maria, Marino Bruno, Vicari Stefano, Coleman Karlene, Cubells Joseph F, Ousley Opal Y, Carmel Miri, Gothelf Doron, Mekori-Domachevsky Ehud, Michaelovsky Elena, Weinberger Ronnie, Weizman Abraham, Kushan Leila, Jalbrzikowski Maria, Armando Marco, Eliez Stéphan, Sandini Corrado, Schneider Maude, Béna Frédérique Sloan, Antshel Kevin M, Fremont Wanda, Kates Wendy R, Belzeaux Raoul, Busa Tiffany, Philip Nicole, Campbell Linda E, McCabe Kathryn L, Hooper Stephen R, Schoch Kelly, Shashi Vandana, Simon Tony J, Tassone Flora, Arango Celso, Fraguas David, García-Miñaúr Sixto, Morey-Canyelles Jaume, Rosell Jordi, Suñer Damià H, Raventos-Simic Jasna, International 22q11.2DS Brain and Behavior Consortium, Epstein Michael P, Williams Nigel M, Bassett Anne S

Аннотация

Schizophrenia occurs in about one in four individuals with 22q11.2 deletion syndrome (22q11.2DS). The aim of this International Brain and Behavior 22q11.2DS Consortium (IBBC) study was to identify genetic factors that contribute to schizophrenia, in addition to the ~20-fold increased risk conveyed by the 22q11.2 deletion. Using whole-genome sequencing data from 519 unrelated individuals with 22q11.2DS, we conducted genome-wide comparisons of common and rare variants between those with schizophrenia and those with no psychotic disorder at age ≥25 years. Available microarray data enabled direct comparison of polygenic risk for schizophrenia between 22q11.2DS and independent population samples with no 22q11.2 deletion, with and without schizophrenia (total n = 35,182). Polygenic risk for schizophrenia within 22q11.2DS was significantly greater for those with schizophrenia (padj = 6.73 × 10-6). Novel reciprocal case-control comparisons between the 22q11.2DS and population-based cohorts showed that polygenic risk score was significantly greater in individuals with psychotic illness, regardless of the presence of the 22q11.2 deletion. Within the 22q11.2DS cohort, results of gene-set analyses showed some support for rare variants affecting synaptic genes. No common or rare variants within the 22q11.2 deletion region were significantly associated with schizophrenia. These findings suggest that in addition to the deletion conferring a greatly increased risk to schizophrenia, the risk is higher when the 22q11.2 deletion and common polygenic risk factors that contribute to schizophrenia in the general population are both present.

Предметные рубрики MeSH

Adult Case-Control Studies Cohort Studies DiGeorge Syndrome Humans Psychotic Disorders Schizophrenia

Genetic contributors to risk of schizophrenia in the presence of a 22q11.2 deletion.

Ошибки и ограничения

Аннотация

Предметные рубрики MeSH