Heritability, Genetics and Personality

How large is the human genome

Approximately 3 billion base pairs

How many protein-coding genes do humans have?

About 20,000

What are introns and exons?

Exons are coding regions

Introns are non-coding regions within genes

What is “junk DNA”?

DNA sequences that do not code for proteins (though some may have regulatory roles)

How many chromosome pairs do humans have?

23 pairs

What are autosomes?

The first 22 pairs of chromosomes

What is a single nucleotide polymorphism?

A variation at a single base pair in the DNA sequence

How many copies of each gene does an individual have?

Two (one from each parent)

How many genotypes are possible with two alleles (A and T)?

Three: AA, TT, AT

What are the two main types of genetic studies?

Heritability studies and molecular genetic studies

What key question do heritability studies ask?

How much variation in a trait is due to genetic differences

What key question do molecular genetic ask?

Which specific genetic variants influence a trait

How does genetic similarity change in family studies?

It decreases with distance from the index case

What can family studies estimate?

The role of genetic variation in behaviour

How common are twin births?

About 1 in 85 births

What proportion of twins are monozygotic?

~1/3

What proportion of twins are dizygotic?

~2/3

What do twin and adoption studies estimate?

The relative contributions of genes and environment

What is the heritability coefficient (h2)?

The proportion of variance in a trait attributable to genetic variation

What did Bouchard & McGue (1981) find about kinship correlations for intelligence)

Highest correlation found in monozygotic twins, correlation scores are always lower if raised apart

What did Loehlin (1982) find about kinship correlations for extraversion?

Highest correlation score in MZ twins but big decrease in correlation when raised apart

What did Loehlin (1982) find about kinship correlations for neuroticism?

Higher correlation in MZ twins raised apart

What do those three studies tell us?

Genetic influence: if correlations remain high when raised apart (especially for MZ twins)

Shared environment: If correlations drop substantially when raised apart

Gene-environment interaction: Complex patterns suggest interaction effects

What did Bouchard (2004) conclude about personality heritability?

Personality traits show moderate heritability (~40%)

Does personality heritability change across adulthood?

It remains fairly stable after early adulthood

Why might intelligence show higher heritability later in life?

Individuals increasingly select environments consistent with genetic predispositions

Typical heritability estimate for personality from twins studies?

~0.4 (40%)

Typical heritability estimate for personality from family/ adoption studies

~0.3 (30%)

What is the heritability for mental ability?

20-80% varies by age- low as a child

Why do heritability estimates vary across studies?

Differences in samples, methods, environments and assumptions

What do molecular genetic studies investigate?

Specific genetic variants or chromosomal regions affecting traits

How do they differ from heritability studies?

Heritability partitions variance; molecular studies identify variants

What are the three main molecular approaches?

Linkage analysis, candidate-gene studies and Genome Wide Association Studies (GWAS)

When is linkage analysis most useful?

Rare traits with simple genetic architecture and large effects

How does linkage analysis work?

Test whether genes and traits are inherited together in families

Why did linkage work well for diseases?

Diseases often involve single genes with large effects

What do candidate-gene studies test?

Associations between pre-selected genes and traits

What is a biological prior?

An evidence-based expectation that a gene influences a trait

What is linkage disequilibrium (LD) tagging?

Using nearby genetic markers inherited together with a target gene

why is adequate sample size important?

Effects are very small and require high statistical power

What confounds must be controlled?

Ancestry, age, sex, and other demographic variables

Lesch et al. (1996) examined which gene?

5HTT (serotonin transporter) with anxiety-related traits

What was the finding for 5HTT?

Short allele associated with reduced serotonin function and higher anxiety

Ebstein et al. (1996) looked at which gene?

DRD4 (dopamine D4 receptor)

What was associated with the DRD4-7 allele?

reduced dopamine binding and increased novelty seeking

What did Munafo et al. (2003) conclude on 5HHT and DRD4?

Many findings failed to replicate

Only small effect of 5HTT on trait anxiety

No effect on DRD4 gene on novelty seeking

Typical variance explained by genes?

less than 3%

Why did DRD4 findings fail to replicate?

Population stratification and selective reporting

What does Genome-wide association studies do?

Scans the entire genome for SNP-trait associations

Is GWAS hypothesis drive?

No- hypothesis-light

Why is the significance threshold so strict?

To correct for massive multiple testing

What is a typically GWAS sample size?

100,000+ participants

What do GWAS “hits” usually represent?

Genomic regions in linkage disequilibrium, not necessarily causal genes

On a manhattan plot what do the dots represent?

Single nucleotide polymorphism

On a manhattan plot what do the dots below the red line mean?

No association

On a manhattan plot what do the dots above the red line mean?

Could be associated with the trait looking at

How many loci did Smith et al. (2016) find for neuroticism?

Nine loci

Why are replication issues common?

Personality traits are highly polygenic

What is SNP heritability?

Proportion of trait variance explained by all common SNPs

What are gene-set/ pathways analyses?

Tests of whether biological pathways showed enriched genetic signal

What is polygenic risk scoring?

Combining effects of many SNPs into a single genetic score

What is G x E interaction?

When the effect of an environment depends on genotype

Why study G x E?

Genes influence sensitivity to environments

What gene did Caspi et al. (2003) study?

5HTT

What environmental factor was studied?

Life stress / maltreatment

What was the key finding?

Maltreatment increased depression risk, moderated by genotype