Genetics of other disorders

Question 1

Autism

Answer 1

• recurrence rate in siblings is 2-8% higher-50x higher
• 2 siblings with autism= 25-30%-300x higher
• 60% concordance in MZ twins, 0% DZ for classic autism
• autistic phenotype is 92% in MZ and 10% in DZ pairs- 90% heritability

Question 2

Autism genes

Answer 2

• chromosome 2,7 and 15
• seen more in fragile X
• non-genetic influences are likely to play an important role in determining the pattern of phenotype in autism

Question 3

ADHD

Answer 3

• risk to first degree relatives= 15-60% 2-6 relative risk
• risk to second degree relatives = 3-9% 0.5-0.8 relative risk
• heritability 70-80%
• risks are highest for male relatives

Question 4

Personality disorders

Answer 4

• 50% is non-shared, person specific environmental variation
• antisocial PD has the highest heritability -60-70%
• a variant of trytophan hydroxylase gene (codes for serotonin enzyme) is associated with low 5-HIAA in CSF and suicide attempts in violent criminal offenders

Question 5

Panic disorders

Answer 5

• lifetime prevalence is 4.7%

- heritability is 0.43

Question 6

Social phobia

Answer 6

• 10x risk in first degree relatives with general social phobia
• specific phobias are 3-4x more common in 1st degree relatives

Question 7

Alcoholism

Answer 7

• risk in families may be up to 4-6x higher than in the general population
• 3-4x higher in adopted children- no protective effect being raised away from alcoholic parents
• genetic risk is higher in males
• ADH4 is associated with earlier onset drinking

Question 8

GABRA2

Answer 8

• on chromosome 4p

- associated with alcohol dependence

Question 9

Alcohol dehydrogenase

Answer 9

• major metabolic enzyme for alcohol, catalyzing its breakfdown into acetaldehyde- further metabolised to ALDH
• ADH and ALDH have variants associated with ‘flushing’ reaction

Question 10

OCD

Answer 10

-early onset suggests higher genetic risk for family member (before age of 18)
-fathers were 3x as likely as mothers to receive a diagnosis of OCD for probands with severe childhood OCD
-increased severity and chronicity appears to increase risk
-risk to first degree relatives onset before 18- 10-35%
-onset after 18- no increased risk to 15%
MZ twins- 53-87%
DZ twins 22-47%

Question 11

Tourettes

Answer 11

100 fold increase in risk for offspring to 25%

-general pop is 0.25%

Question 12

Anorexia nervosa

Answer 12

10 fold increase to 5% in offspring

-0.5% in general population