Genetics for Epidemiologists Lecture 5: Analysis of Genetic Association Studies National Human Genome Research Institute National Institutes of Health U.S. Department of Health and Human Services U.S. Department of Health and Human Services National Institutes of Health National Human Genome Research Institute Teri A. Manolio, M.D., Ph.D. Director, Office of Population Genomics and Senior Advisor to the Director, NHGRI, for Population Genomics
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Genetics for Epidemiologists Lecture 5: Analysis of Genetic Association Studies
Genetics for Epidemiologists Lecture 5: Analysis of Genetic Association Studies. National Human Genome Research Institute. U.S. Department of Health and Human Services National Institutes of Health National Human Genome Research Institute. National Institutes of Health. - PowerPoint PPT Presentation
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Genetics for Epidemiologists
Lecture 5: Analysis of Genetic Association Studies
National Human Genome Research
Institute
National Institutes of
Health
U.S. Department of Health and
Human Services
U.S. Department of Health and Human Services
National Institutes of HealthNational Human Genome Research
InstituteTeri A. Manolio, M.D., Ph.D.
Director, Office of Population Genomics andSenior Advisor to the Director, NHGRI,
for Population Genomics
Topics to be Covered
• Discrete traits and quantitative traits
• Measures of association
• Detecting/correcting for false positives
• Genotyping quality control
• Quantile-quantile (Q-Q) plots
• Odds ratios: allelic and genotypic
• Models of genetic transmission
• Interactions: gene-gene, gene-environment
Larson, G. The Complete Far Side. 2003.
Quantitative Genetics
“…concerned with the inheritance of those differences between individuals that are of degree rather than of kind…”
Quantitative Qualitative
Falconer and Mackay, Quantitative Genetics 1996.
Quantitative Genetics
“…concerned with the inheritance of those differences between individuals that are of degree rather than of kind…”
Quantitative Qualitative
Continuous gradation among individuals from one extreme to other
Sharply demarcated types with little connection by intermediates
Falconer and Mackay, Quantitative Genetics 1996.
Quantitative Genetics
“…concerned with the inheritance of those differences between individuals that are of degree rather than of kind…”
Quantitative Qualitative
Continuous gradation among individuals from one extreme to other
Sharply demarcated types with little connection by intermediates
Effects of genes are small
Effects of genes are large
Falconer and Mackay, Quantitative Genetics 1996.
Quantitative Genetics
“…concerned with the inheritance of those differences between individuals that are of degree rather than of kind…”
Quantitative Qualitative
Continuous gradation among individuals from one extreme to other
Sharply demarcated types with little connection by intermediates
Effects of genes are small
Effects of genes are large
Usually many genes Single genes inherited in Mendelian ratios?
Falconer and Mackay, Quantitative Genetics 1996.
Inheritance Models in Single Gene Trait
A
a
Genotype Group
Model AA Aa aa
Inheritance Models in Single Gene Trait
Genotype Group
Model AA Aa aa
A is Dominant
Inheritance Models in Single Gene Trait
Genotype Group
Model AA Aa aa
A is Dominant
Inheritance Models in Single Gene Trait
Genotype Group
Model AA Aa aa
A is Dominant
A is Recessive
Inheritance Models in Single Gene Trait
Genotype Group
Model AA Aa aa
A is Dominant
A is Recessive
A is Co-Dominant
Inheritance Models in Single Gene Trait
Inheritance Models in Quantitative Trait
A x increase in height
a x decrease in height
Population Mean
Model -x 0 +x
Inheritance Models in Quantitative Trait
Population Mean
Model -x 0 +x
A is Completely Dominant
aa
AAAa
Inheritance Models in Quantitative Trait
Population Mean
Model -x 0 +x
A is Completely Dominant
aa
AAAa
A is Partially Dominant
aa Aa AA
Inheritance Models in Quantitative Trait
Population Mean
Model -x 0 +x
A is Completely Dominant
aa
AAAa
A is Partially Dominant
aa Aa AA
A is Not (Co-) Dominant
aa Aa AA
Inheritance Models in Quantitative Trait
Population Mean
Model -x 0 +x
A is Completely Dominant
aa
AAAa
A is Partially Dominant
aa Aa AA
A is Not (Co-) Dominant
aa Aa AA
A is Over-Dominant
aa AA Aa
Inheritance Models in Quantitative Trait
Quantitative Traits with Published GWA Studies (16 - 34)