Transcript Lecture 2 - King`s College London

Psychiatric Disorder: Is It All In
The Genes?
Peter McGuffin
MRC SGDP Centre
Institute of Psychiatry, King’s
College London
Why might a disorder run in
families?
 Shared genes
 Shared environment
 A combination of the two
behaviour
Natural experiments teasing apart
genes and environment
Twin studies : is there more similarity
monozygotic ( one egg) than dizygotic ( two
egg) pairs?
Adoption studies: do individuals resemble
their biological relatives more than adopting
relatives?
MZ TWINS
 MZ (monozygotic)
twins have 100% of
their genes in common
(they’re ‘natural
clones’)
 Shared environment
also makes them
similar
DZ TWINS
 DZ (dizygotic) twins
have 50% shared
genes
 They also share
environment to
roughly the same
extent as MZ twins
MZ and DZ Twin Similarity Expressed as
Correlations
childhood fatigue
ADHD
DZ
MZ
bulimic symptoms
depression (unipolar)
manic depression (bipolar)
autism
schizophrenia
0
0.2
0.4
0.6
0.8
1
Types of Gene Environment
Interplay
 Coaction
 Additive
 Interaction
 Multiplicative
 Covariation
 G & E correlated
Coaction
 Phenotype= Genes (G) + Environment (E)
Shared
Non-shared
GE Correlation Vs Interaction
 Correlation: genetic influence on exposure
to different environments
 Interaction: genetic control of sensitivity to
different environments
Finding genes
 One of the major benefits of the Human Genome
Project is a dense map of markers (“signposts”for
genome searching)
 Linkage studies use genetic markers track genes in
families
 Association studies can pinpoint genes in
populations
Positional cloning
 Linkage(or LD)
 location
prediction
 gene identification
diagnosis
 structure and sequence
 gene product
treatment
Specific genes that interact with
environments
 serotonin transporter, social adversity (and
medication) => depression
 Monoamine oxidase A,childhood
maltreatment => antisocial behaviour
 COMT, cannabis => schizophrenia
The impact of genetics: Post
genomic psychiatry




targeted & tailored treatments
refined diagnosis
understanding of neurobiology
risk prediction and gene-environment
effects
 public perception and stigma