Topic 6 Part 1 Genetic issues in mental health

Question 1

Complex diseases

Answer 1

1. Diseases resulting from complex interactions
   between genes (major genes, polygenes) and
   environmental exposures.
2. Disease transmission in families does not fit a simple Mendelian pattern.
3. Commonly exhibit variable expressivity,
   incomplete penetrance, or age-dependent effects.

Question 2

Variable expressivity

Answer 2

1. The same trait/disorder is expressed differently in different people - mild and severe forms. Example: Neurofibromatosis.
2. Different/many phenotypes associated with the same disease gene/mutation. Example: The same gene can cause OCD in one individual and motor tics in a different individual.

Question 3

Incomplete penetrance

Answer 3

When a person carries a gene, but there is no observable expression or phenotype.

Question 4

Age-dependent effects

Answer 4

Certain disorders have particular ages of onset; psychiatric disorders tend to have a later age of onset.

Question 5

Multifactorial

Answer 5

Phenotype determined by more than one gene, gene-gene interactions, and/or gene-environment interplay.

Question 6

Heterogeneity

Answer 6

Same phenotype caused by different genes or different interactions or variations in the same gene that is associated with differences in disease risk.

Question 7

Penetrance

Answer 7

How often a phenotype appears in an individual with a mutation.

Question 8

_ can be a marker of the severity of the index disorder.

Answer 8

Comorbidity.

Question 9

Assortative mating

Answer 9

1. People tend to prefer similar individuals when choosing a partner, which also includes their health problems.
2. Example: Among people with bipolar disorder, the likelihood their partner will have a history of mood disorder is 70%.

Question 10

Heritability

Answer 10

1. The degree to which genetics contributes to the overall variability of a disorder within a population.
2. A population statistic that expresses the proportion of the total phenotypic variation of a trait that is due to genetics.

Question 11

Heritability can be assessed through _

Answer 11

Familial aggregation studies, twin studies, and adoption studies.

Question 12

Copy number variants (CNVs)

Answer 12

1. Variations in stretches of DNA found throughout the genome. These are often deletions or duplications.
2. Most are benign, but rare large or de novo duplications or deletions have been associated with autism, epilepsy, learning disabilities, and schizophrenia.
3. These can be tested for, although the testing is very expensive.

Question 13

The easiest way to measure heritability is through _

Answer 13

Twin studies - compare the concordance of monozygotic (identical) twins versus dizygotic (fraternal) twins.

Question 14

Epigenome/epigenetics

Answer 14

1. Biochemical factors that alter gene expression but do not involve changes in the underlying DNA sequence.
2. Examples: Alterations in methylation patterns or histone proteins.
3. Epigenetic mechanisms have been suggested as possibly important in the onset of schizophrenia.

Question 15

For a given trait, a heritability of 0.5 means that _

Answer 15

50% of the variability in the population can be said to be related to genes.

Question 16

Increased susceptibility for developing Alzheimer’s disease is primarily associated with mutations on the _ gene on chromosome 19.

Answer 16

APOE.

Question 17

_ syndrome has been associated with schizophrenia.

Answer 17

Velocardiofacial.

Question 18

Candidate genes

Answer 18

1. Identify genes involved in a biochemical process and then evaluate them for functional changes in affected individuals.
2. Examples: Dopamine transmitters, serotonin receptors.

Question 19

Susceptibility genes are often looked for by _

Answer 19

Association studies.

Question 20

Genome Wide Association Studies (GWAS)

Answer 20

1. Tests that look for areas of the genome associated with a certain disease by comparing the genomes of affected and unaffected populations.
2. Can help to identify susceptibilty genes of small effect. Disadvantage: Hard to replicate.

Question 21

Pleiotropy

Answer 21

An effect in which a single-gene disorder results in problems expressed in many tissues and functions.

Question 22

Features of _ are consistent with early life reprogramming of genes in response to environmental effects.

Answer 22

DNA methylation.

Question 23

Psychiatric illness are often said to be _

Answer 23

Polygenic (many genes are involved, each of which as a small effect).

Question 24

The DSM focuses on defining psychiatric disorders in terms of _

Answer 24

Symptoms or phenotype (defining by etiology is considered too complex at this time).

Question 25

The association between bipolar disorder and schizophrenia is an example of a _

Answer 25

Cross-disorder overlap.

Question 26

Empiric risk

Answer 26

1. A risk figure for a person being affected with a (usually) multifactorial disorder, obtained by observation and experience of many families where people have that disorder - based on statistics for a population.
2. Usually expressed as a range.
3. Identifying and explaining empiric risks is what much of genetic counseling is based on.

Question 27

Lithium, often administered to people with bipolar disorder, is associated with _ in fetuses.

Answer 27

Transposition of the great arteries.

Question 28

Endophenotypes

Answer 28

1. Phenotypes associated with psychiatric illness but are more quantifiable, more common, and seen in more widespread conditions.
2. Example: p50 EEG wave in schizophrenia, low response to alcohol.

Question 29

Behavioral phenotypes in genetic disorders

Answer 29

1. Prader-Willi syndrome has an association with OCD, particularly compulsive eating.
2. Neurofibromatosis has an association with ADHD.
3. Down syndrome has an association with early-onset Alzheimer’s.

Question 30

Which statement or condition best reflects multifactorial inheritance?

Answer 30

The susceptibility to a problem is an inherited trait but development of the problem is related to environmental conditions.