Genetics of Schizophrenia Flashcards
Understand the relative contributions that the following have made to the understanding of the genetic basis of schizophrenia: linkage studies, candidate gene studies, GWAS, CNV studies, exome studies, transcriptomics
When is the typical onset of schizophrenia?
Late adolescence or early adulthood
State the 3 main symptom domains of schizophrenia
Positive symptoms, negative symptoms, cognitive problems
State some positive symptoms of schizophrenia
Delusions, hallucinations, disorganised speech
State some negative symptoms of schizophrenia
Social withdrawal, apathy, emotional blunting
State some cognitive problems of schizophrenia
Difficulties with memory, attention, and processing speed
Give at least 5 risk factors implicated in schizophrenia
Genetics, paternal age, maternal famine, infection while pregnant, season of birth, hypoxia at birth, urban dwelling, adolescent cannabis use, migration
State the monozygotic twin concordance of schizophrenia
48%
What is a linkage study?
A study looking at the co-inheritance of genetic markers on chromosomes in families with high incidence of a disease to try and identify markers linked to that disease
Why are dopamine receptor D2 genes or associated genes candidate genes in schizophrenia?
Most drugs for schizophrenia target dopamine receptor D2
What is the aim of genome wide association studies (GWAS)?
To identify single base variants (SNPs) associated with a clinical condition
Which main gene areas have been implicated in schizophrenia by genome wide association studies?
Genes involved in glutamate neurotransmission, synaptic plasticity, and voltage-gated calcium channel subunits
Where are most SNPs implicated in schizophrenia expressed?
The brain and immune tissues, particularly the MHC locus
Name 2 rare schizophrenia alleles
Disrupted in schizophrenia 1 (DISC1) and 22q11 deletion syndrome
Which mental disorders does disrupted in schizophrenia 1 (DISC1) predispose to?
Schizophrenia, bipolar disorder, recurrent major depression, adolescent conduct disorder, anxiety disorder, alcohol abuse
What is disrupted in schizophrenia 1 (DISC1)?
A translocation between chromosome 1 and chromosome 11
What does 22q11 deletion syndrome cause?
Velo-cardial facial syndrome, characterised by hypoparathyroidism, and underdeveloped or absent thymus (and consequent immune problems), heart defecrs, and a cleft lip or palate - as well as schizophrenia in 1/3 of patients
What type of study identifies deletion syndromes?
Copy number variant studies
Which disorders is 15q11 deletion associated with?
Autism spectrum disorder, Angelmann syndrome, Prader-Willi syndrome
What is next generation sequencing used to identify?
De novo mutations - those found in the child but not either parent
Describe the results of Fromer et al & Purcell et al’s 2014 studies into de novo mutations in schizophrenia
De novo mutations were not more common in schizophrenics, but mutations were more commonly located in the ARC, MNDAr, and FMRP pathways (synaptic pathways)
What does transcriptomics look at?
All the genes present in and expressed by a tissue
State the brain regions implicated in schizophrenia
Frontal and temporal cortices
Name a candidate gene in schizophrenia identified from expression profiling studies
Zinc transporter ZnT3
Describe the relationship between zinc and brain function
Suboptimal zinc nutrition during gestation in rats causes long-term effects on brain function (Aimo et al, 2010), and zinc supplementation is beneficial in major depression (Nowak et al, 2011)
Describe the relationship between ZnT3 and schizophrenia
ZnT3 has been identified as a candidate gene in expression profiling, and there are four SNPs associated with ZnT3 and schizophrenia - all of which are consistent with a dominant model for disease penetrance
Where do the candidate differentially expressed genes implicated in schizophrenia appear to localise to? (Maycox et al, 2009)
The synaptome
