Third Bangalore School on Population Genetics and Evolution
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GWAS in structured populations
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The agenda
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Like begets like Sir Francis Galton et al.
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How many genes?
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The simplest model possible Fisher 1918
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Dominance and epistasis
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Average effect
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Variance decomposition
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Heritability
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Typically estimated from parent-offspring regression
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How do we map genes?
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Linkage mapping
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So why do it?
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...if sample size is large enough...
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The Human Genome Project meant markers were no longer limiting...
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The promise
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The HapMap Project
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Coronary artery disease
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The GWAS debacle
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...height has a heritability of 80%!
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A random-effects model is used to estimate variance components
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In other words. ..
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Could have told you so!
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"The world's most expensive test of the mutation-selection balance hypothesis"
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There were Cassandras. ..
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Population structure confounding in GWAS
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GWAS works!
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Science
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Dealing with "population structure"
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We understand this now...
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The problem of fine mapping
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..but peak is far from the obvious candidate...
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Including two co-factors eliminates spurious peak
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A simulation example. ..
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Some obvious extensions
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Plants are not humans
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Adaptation is different from disease
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What about skin color?
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Cabo Verde
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Genome-wide markers explain much more
Description:
Explore a comprehensive lecture on Genome-Wide Association Studies (GWAS) in structured populations, delivered by Magnus Nordborg at the Third Bangalore School on Population Genetics and Evolution. Delve into the historical context of genetic inheritance, starting with Sir Francis Galton's observations, and progress through the development of GWAS methodology. Examine the challenges and successes of GWAS, including the impact of the Human Genome Project and HapMap Project. Analyze the complexities of population structure confounding and fine mapping in GWAS. Investigate case studies in coronary artery disease, human height, and skin color adaptation. Gain insights into the differences between plant and human genetics, and understand how genome-wide markers contribute to explaining genetic variation.