SPRING Genetics of Psychiatric Disorders Flashcards
what is the ACE model
twin studies
a = additive genetic variance (0.5 DZ, 1.0 MZ)
c = common shared environment (1.0)
e - non shared environment (0.0)
similarity based on genetics in proportion to the environment
what is heritability
proportion of variance in a phenotype explained by purely genetic effects
estimated after accounts for phenotypic variance due to shared and non shared environment
- proportion variance explained after accounting for C and E
concordance between MZ and DZ (not two MZ)
what do genetic association studies look into
if specific phenotypes are more prevalent in certain groups of individuals who have certain genetic variants/sets of variants
are certain variants more likely to be given a diagnosis or hold specific characteristics ie PCR and soutehr blot/genome assoc
heritability of ASD
ASD = 93%
heritability of schizophrenia
81%
heritability of major depressive disorder
37%
heritability of bipolar disorder
1.5%
what is considered a wear genetic assoc/weak heritability
no real classification with as to what counts but generally accepted to be around 50%
what is global lifetime prevalance
prevalance of a disorder across lifespan
not in one point in time but accross life
if resrticted to certain cultures or varies across the world then likely to hold more of an environmental influence
gives indirect idea of whether something is sufficiently common across the worlds population
what is point prevalence
prevalence of a disorder in this moment/specific time frame
problem with endophenotypes and clinical disorders
clinical disorders share endophenotypes
ie exec dysfunction shared in schiz and bipolar
disorders are not independent and share ensophenic features - focus on heritability of the phenotype not the disorder
problem with DSM classification of clinical disorders
not based on exact diagnosis but reflects current understanding and popular thoughts within society
ie homosexuality once thought to be a disorder
serretti et al 2013 shared genetic disorders
30,000 individuals with different psychiatric conditions studied
found shared underlying genetic variations
‘disease vunerabiltity’
genetic variations of autism
simplex
multiplex
explain simplex autism
one proband (example) in the family due to de novo variation 20% or 1 5th of all individuals ie problem in DNA replication process cause copy no variations
explain multiplex autism
multiple individuals in one family affected - autistic traits passed down over generations but not enough for full clinical diagnosis
eventually, enough small sequence variants for individual to pass autistic threshold
types of gene hunting
guided missiles approach
genome wide approach
what is the guided missiles approach to gene hunting
have a clear idea of a gene and its possible function from animal studies
gene studies and PCR
what is the genome wide approach
dont take into account previous knowledge and study every genetic variation and whatever appears significant is thought to be assoc with that specific disorder
retrofixed
ie genome wide studies and microarrays
key genes in autism
SAFRI and AutismKB
gene links and networks in autism
lots of genes assoc with autism
some more prevalent than others
some acts as nodes to network of other genes ie HTR2A
looking beyond assoc of just one gene and now look at interactions
what is the 3 chambers social approach task for autism
animal study for genes on autism
knockout mouse given choice of 2 plexiglass chambers
one chamber holds novel object and conspecific mouse and the other just a novel object
autism thought to prefer lone chamber
- how do you look into if a disorder has a genetic link
look at heritability and global lifetime prevalence (anything > 1%)
- how do you look at inheritence in families
simplex or multiplex examples
look at big or small variations
