SPRING Genetics of Psychiatric Disorders

Question 1

what is the ACE model

Answer 1

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

Question 2

what is heritability

Answer 2

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)

Question 3

what do genetic association studies look into

Answer 3

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

Question 4

heritability of ASD

Answer 4

ASD = 93%

Question 5

heritability of schizophrenia

Answer 5

81%

Question 6

heritability of major depressive disorder

Answer 6

37%

Question 7

heritability of bipolar disorder

Answer 7

1.5%

Question 8

what is considered a wear genetic assoc/weak heritability

Answer 8

no real classification with as to what counts but generally accepted to be around 50%

Question 9

what is global lifetime prevalance

Answer 9

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

Question 10

what is point prevalence

Answer 10

prevalence of a disorder in this moment/specific time frame

Question 11

problem with endophenotypes and clinical disorders

Answer 11

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

Question 12

problem with DSM classification of clinical disorders

Answer 12

not based on exact diagnosis but reflects current understanding and popular thoughts within society
ie homosexuality once thought to be a disorder

Question 13

serretti et al 2013 shared genetic disorders

Answer 13

30,000 individuals with different psychiatric conditions studied
found shared underlying genetic variations
‘disease vunerabiltity’

Question 14

genetic variations of autism

Answer 14

simplex

multiplex

Question 15

explain simplex autism

Answer 15

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

Question 16

explain multiplex autism

Answer 16

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

Question 17

types of gene hunting

Answer 17

guided missiles approach

genome wide approach

Question 18

what is the guided missiles approach to gene hunting

Answer 18

have a clear idea of a gene and its possible function from animal studies
gene studies and PCR

Question 19

what is the genome wide approach

Answer 19

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

Question 20

key genes in autism

Answer 20

SAFRI and AutismKB

Question 21

gene links and networks in autism

Answer 21

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

Question 22

what is the 3 chambers social approach task for autism

Answer 22

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

Question 23

1. how do you look into if a disorder has a genetic link

Answer 23

look at heritability and global lifetime prevalence (anything > 1%)

Question 24

2. how do you look at inheritence in families

Answer 24

simplex or multiplex examples

look at big or small variations

Question 25

3. how do you test the assoc of genes with a disorder

Answer 25

PCR, single genetic variation, assoc with condiiton or large genetic variation using genome wide
animal studies