Biomaterial Database

Whole-genome sequencing of monozygotic twins discordant for schizophrenia indicates multiple genetic risk factors for schizophrenia. 2017

Jinsong Tang, and Yu Fan, and Hong Li, and Qun Xiang, and Deng-Feng Zhang, and Zongchang Li, and Ying He, and Yanhui Liao, and Ya Wang, and Fan He, and Fengyu Zhang, and Yin Yao Shugart, and Chunyu Liu, and Yanqing Tang, and Raymond C K Chan, and Chuan-Yue Wang, and Yong-Gang Yao, and Xiaogang Chen

Institute of Mental Health, National Clinical Research Center for Mental Health Disorders and National Technology Institute of Psychiatry, and Key Laboratory of Psychiatry and Mental Health of Hunan Province, The Second Xiangya Hospital, Central South University, Changsha 410011, China.

Schizophrenia is a common disorder with a high heritability, but its genetic architecture is still elusive. We implemented whole-genome sequencing (WGS) analysis of 8 families with monozygotic (MZ) twin pairs discordant for schizophrenia to assess potential association of de novo mutations (DNMs) or inherited variants with susceptibility to schizophrenia. Eight non-synonymous DNMs (including one splicing site) were identified and shared by twins, which were either located in previously reported schizophrenia risk genes (p.V24689I mutation in TTN, p.S2506T mutation in GCN1L1, IVS3+1G > T in DOCK1) or had a benign to damaging effect according to in silico prediction analysis. By searching the inherited rare damaging or loss-of-function (LOF) variants and common susceptible alleles from three classes of schizophrenia candidate genes, we were able to distill genetic alterations in several schizophrenia risk genes, including GAD1, PLXNA2, RELN and FEZ1. Four inherited copy number variations (CNVs; including a large deletion at 16p13.11) implicated for schizophrenia were identified in four families, respectively. Most of families carried both missense DNMs and inherited risk variants, which might suggest that DNMs, inherited rare damaging variants and common risk alleles together conferred to schizophrenia susceptibility. Our results support that schizophrenia is caused by a combination of multiple genetic factors, with each DNM/variant showing a relatively small effect size.

UI	MeSH Term	Description	Entries
D008297	Male		Males
D010375	Pedigree	The record of descent or ancestry, particularly of a particular condition or trait, indicating individual family members, their relationships, and their status with respect to the trait or condition.	Family Tree,Genealogical Tree,Genealogic Tree,Genetic Identity,Identity, Genetic,Family Trees,Genealogic Trees,Genealogical Trees,Genetic Identities,Identities, Genetic,Tree, Family,Tree, Genealogic,Tree, Genealogical,Trees, Family,Trees, Genealogic,Trees, Genealogical
D005260	Female		Females
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000073336	Whole Genome Sequencing	Techniques to determine the entire sequence of the GENOME of an organism or individual.	Complete Genome Sequencing,Genome Sequencing, Complete,Genome Sequencing, Whole,Sequencing, Complete Genome,Sequencing, Whole Genome
D000091042	Reelin Protein	It is an EXTRACELLULAR MATRIX serine protease that plays an important role in the development of the central nervous system. It regulates neuronal migration and microtubule function.	RELN Protein,Reeler Protein,Protein, RELN,Protein, Reeler,Protein, Reelin
D000328	Adult	A person having attained full growth or maturity. Adults are of 19 through 44 years of age. For a person between 19 and 24 years of age, YOUNG ADULT is available.	Adults
D012559	Schizophrenia	A severe emotional disorder of psychotic depth characteristically marked by a retreat from reality with delusion formation, HALLUCINATIONS, emotional disharmony, and regressive behavior.	Dementia Praecox,Schizophrenic Disorders,Disorder, Schizophrenic,Disorders, Schizophrenic,Schizophrenias,Schizophrenic Disorder
D014430	Twins, Monozygotic	Two off-spring from the same PREGNANCY. They are from a single fertilized OVUM that split into two EMBRYOS. Such twins are usually genetically identical and of the same sex.	Twins, Identical,Identical Twin,Identical Twins,Monozygotic Twin,Monozygotic Twins,Twin, Identical,Twin, Monozygotic
D056915	DNA Copy Number Variations	Stretches of genomic DNA that exist in different multiples between individuals. Many copy number variations have been associated with susceptibility or resistance to disease.	Copy Number Polymorphism,DNA Copy Number Variant,Copy Number Changes, DNA,Copy Number Polymorphisms,Copy Number Variants, DNA,Copy Number Variation, DNA,DNA Copy Number Change,DNA Copy Number Changes,DNA Copy Number Polymorphism,DNA Copy Number Polymorphisms,DNA Copy Number Variants,DNA Copy Number Variation,Polymorphism, Copy Number,Polymorphisms, Copy Number