Lab 13: Association Genetics
Goals
• Use a Mixed Model to determine genetic
associations.
• Understand the effect of population structure
and kinship on associations.
• Use Trait Analysis by aSSociation, Evolution
and Linkage (TASSEL) to calculate phenotypegenotype associations.
Mixed Model
effects of
background SNPs
phenotype
(response variable)
of individual i
effect of target SNP
Family effect
(Kinship
coefficient)
Population Effect (e.g., Admixture
coefficient from Structure or
values of Principal Components)
Population Structure
Cases
Controls
Pop 1
Genotype
Pop 1
TT
AT
AA
Pop 2
Pop 2
• Unequal distribution of alleles unrelated to disease
between cases and controls.
• Any allele more common in diseased population may
spuriously appear to be associated with disease.
Principal Component Analysis (PCA)
• PCA is a computationally efficient way to quantify
population structure (Q).
• PCA reduces dimensionality of the data so that the
correlated variables are transformed into uncorrelated
variables called principal components.
• PC1 captures as much of the variation as possible and
proceeds with PC2, PC3….
• Requires elimination of monomorphic markers and
imputation of missing values.
Imputing Missing Genotypes
From Isik and Wetten 2011 Workshop on Genomic Selection
Typically accomplished with software such as IMPUTE, PLINK, MACH, BEAGLE, and
fastPHASE
PCA and Population Structure
0.2
0.1
A
0.4
B
C
D
0.0
0.1
0.2
-0.1
0.0
0.0
Dean
Homathko
Lilloet
PC1
Klinaklini
Skagit
Tahoe
Willamette
Columbia
Puyallup
Skykomish
Skagit
Lilloet
Homathko
Klinaklini
Dean
Skykomish
Puyallup
Columbia
-0.2
-0.1
-0.3
-0.2
Willamette
Tahoe
-0.4
-0.2
0.0
0.2
0.4
-0.2
Puyallup
Skykomish
Skagit
Lilloet
Homathko
Kliniklini
Dean
-0.4
-0.4
-0.2
0.0
PC2
0.2
0.4
-0.4
-0.2
0.0
0.2
0.4
Problem 1 (revised) Use the Tassel Tutorial Data to explore how to
perform association genetic analyses for some commercially-important
Maize phenotypes: flowering time, ear height, and ear width.
A. Which traits have significant associations? Which chromosomes are
associated with each trait?
A. Are there any patterns to the locations of the significant SNPs within
the gene or chromosomes (e.g., are the significant SNPs clustered or
dispersed, where in the gene do they occur)? Do similar
chromosomal regions show associations with different traits? What
are some possible reasons for these patterns?
A. How do the corrections for population structure and kinship change
the associations? Why?