HC 11 Flashcards
What is imaging genetics?
Combines brain imaging and genetics to identify and characterize genetic variants (genotypes= genetic makeup) associated with inter-individual variation in brain structure and function (phenotype= observable characteristic) to relate this to behavioral traits.
This is to gain insight into genetic regulation of the human brain.
What are some summary neuroimaging phenotypes?
-Morphology
-Function
-Connectome
What is morphology?
Volume/concentration of gray/white matter, cortical thickness, cortical area. This is called the gyrification index.
What is function?
Extent of activation/deactivation. This gives a contrast map, measures characterizing spontaneous brain activity.
What is connectome?
Anisotropy, tractography. Functional/effective connectivity measures or complex network measures.
What are genetics?
DNA= Deoxyribonucleic acid. Spiraling, complex mollecule containing base pairs.
Gene= Length of DNA that holds instructions for making one protein.
Chromosome= Long strand of DNA, coiled and wrapped up, contains many genes.
What are genetic variations?
Polymorphism= variation in a gene or segment of DNA
Single nucleotide polymorphism= variation of single base pair at specific genomic location: some individuals have one nucleotide, others have different nucleotide at that location.
What do twin studies provide?
Allows determining magnitude of genetic & environmental factors contributing to trait variance.
Compare trait resemblance in genetically identical participants with trait resemblance in participants that share only half their genetic material.
If there is a difference in monozygotic twins, then there is an environmental factor at play.
If there is a genetic component at play, then it is expected that the monozygotic twins are more similar than dizygotic twins.
How do we identify genes involved in particular disease/trait/behaviour?
-Family linkage study
-Candidate gene association study
-Genome-wide association study
-Consortia and meta-analytic approaches
What are family linkage studies?
‘Standard’ approach to gene discovery: study families in which disease occurs frequently.
Succesful in identifying disease-susceptibility genes in rare familial diseases.
+mainly succesful for diseases caused by mutations in a single gene
-unsuccesful in more common heritable diseases where many genes interact
What is the candidate-gene approach?
Test specific a priori hypotheses regarding the link between measured variation in a gene and variation in brain structure and function.
One or more SNPs (single nucleotide polymorphisms) for which there is some prior evidence of association with trait or disease are tested against an imaging phenotype.
High statistical power, but incapable of discovering new genes or gene combinations.
What is genome-wide association studies?
Examination of large SNPs across the genome to see if any are associated with specific phenotype.
Can pinpoint genes regardless of whether their function was known before, but low power owing to the number of independent tests performed => correct for multiple testing
Results can serve as input for candidate-gene approach.
What are consortia and meta-analytic approaches?
To increase statistical power and identify consistent genetic effects.
Multi-center consortia combine numerous samples to produce large-scale datasets.
Meta-analytic studies synthesize and combine imaging genetic findings from many cohorts worldwide.
What is polygenic risk scoring?
Incorporates effects of all SNPs across the genome by using a single aggregated quantitative metric based on previously published, publicily available GWA data.
The theoretical bases:
-Multiple risk polymorphisms in same disease-related biological pathway will be more likely to disrupt normal functioning of that pathway
-Multiple risk polymorphisms affecting various biological pathways together will predispose or lead to disease
=> maximization of power within smaller samples
=> provide replication of findings
