Genetics of Mental Disorders Flashcards
What was discovered when children of mothers with and without SCZ were adopted and raised to adulthood?
The children of mothers with SCZ had a much higher chance of developing SCZ
Genetic basis for mental illness
What is the 5 step outline for tracking genetics in mental disorders?
Familial aggregation studies (Is there familial clustering?)
Heritability studies (Is there evidence or a genetic effect?)
Segregation analyses (Is there evidence for a particular genetic model?)
Linkage, association studies (Where is the disease gene?)
Variant frequency, risk magnitude, environmental interactions (How does this gene contribute to disease in the general population?)
What is the objective of family aggregation studies?
Describe the Family interview for genetic studies (FIGS)
To determine whether relatives have an excess frequency of the same disease when compared to the general population
FIGS:
Gather info for as many relatives as possible, start with affected person and scale out (drawing and analysing pedigrees)
Describe the relative risk ratio and how it is calculated?
Rate of disorder in relative of type R / Rate of disorder in the population
The percent chance that a relative of type R (Sibling/cousin/uncle/twin) will develop the disease
Can FIGS determine Heritability?
No, it can determine familiality
Does not necessarily prove something is inherited, just that it runs in the family (religion is also familial)
How is phenotype “calculated”?
What is heritability in this context and how is it calculated?
P = G + E
Phenotype is the genetic makeup of an individual plus the environmental factors important for a particular disorder
Heritability is the proportion of variance for P due to G versus E
H = 2(r MZ - r DZ)
Where r m/d z is the concordance in P between monozygotic and dizygotic twins
What is an Odds Ratio and how is it interpreted?
Odds of something having an effect
=1, nothing
>1 something has more impact on the disorder
Are mental disorders mendelian? How do we know?
No
They don’t follow Mendelian patterns of segregation
What are 3 ways DNA can vary?
SNPs
CNVs
TRPs
Recombination rate is a function of _____
The more _____ two genes are, the ____ likely they are to be transmitted as a unit
physical distance
close together
More
When can we predict who gets a disorder with marker genes?
If the trait gene is close to the marker gene
What gene was found using marker genes relating to ADHD?
LPHN3
Latrophilin 3
Describe two types of association studies
- Family-based analysis
TDT - Examines allele transmission - Case-control analysis
Observe two populations of disease and normal, if a gene is expressed more in disease population it could be associated with the disease
Describe the candidate gene approach
Eg. Ritalin treats ADHD
Ritalin acts on DAT/NET
Therefore, ADHD is associated with DAT/NET
DAT/NET genes become candidates
When performing a GWAS, do each and every SNP require being tested?
No, you can take advantage of linkage and only test haplotype blocks
Blocks = series of adjacent alleles separated by recombination hotspots
