Race, population biology + disease genetics Flashcards
Why is this an area where there is a lot of wrong areas and conteversial?
Results using the techniques and results of human genetics can be misinterpreted to argue unsupported conclusions about group level differences in humans.
Bias in populations used for investigating genetic determinants of disease means results are differentially accurate in different groups of people
What does GWAS work in?
Genetically homogenous populations
Why do we isolate homogenous populations?
For stratification
WHat is PCA?
Principal components analysis, PCA, is a statistical method commonly used in population genetics to identify structure in the distribution of genetic variation across geographical location and ethnic background
Give example of GWAS hits which were population specific
APOE4 variant is associated with 5X higher risk of Alzheimer’s disease in Asians than in Africans
Myocardial Infarction
HapK allele originally associated in Icelandic population
Allele has stronger effect in “African” populations
However, less common, therefore not detected.
Why might alleles have different effects in different populations?
Environment selection for particular allele
Why might SNPs have different effects?
Difference in effect size
Causal SNP poorley tagged
Alleles are rare
DIfferent effect size
Biological effect might be genuinely different
Gene x Environment interaction
Gene x gene interaction
Casual SNP poorly tagged
Biological effect not genuinely different
Linkage disequilibrium patterns are population specific - different populations have different amounts of LD
Different populations even have different amounts of disequilibrium
Alleles are rare
Some alleles have different frequencies in different populations
Almost ALL GWAS associated SNPs (both protective and risk) are more common in European.
SNP catalogues are European focused.
When are PRS less accurate?
BMI prediction loses 60% of its predictive power in individuals of “recent African origin”
PRS also less accurate in poorer individuals than rich
What are the solutions?
Defined genotype arrays in other populations used in GWAS
Larger diversity of GWAS participants
Genotyping arrays designed for diverse participants
WHole genome sequencing
How to deal with stratification?
How to define population
