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Genome-Wide Association Study
GWAS
Ferdinand van ’t Hooft
Cardiovascular Genetics and Genomics Group
Karolinska Institutet, Stockholm, Sweden
http://en.wikipedia.org/wiki/Genome-wide_association_study
Human Genome
Genetic variation
Single Nucleotide polymorphism (SNP)
Allele
- One of two copies of a genetic sequence at a chromosomal
location
- Alleles can be considered according to their frequencies in the
human population:
- Common variants – minor allele frequency (MAF) >5%
- Low frequency variants – MAF 0.5-5%
- Rare variants – MAF <0.5%
-Other terms:
- Polymorphism – MAF>1%
- Mutation – MAF<1%
Linkage disequilibrium
Selections of SNPs representative for LD-blocks in the genome
Linkage study versus association study
Linkage study of a familial hypercholesterolemia (FH) family
Identification of mutations in PCSK9 as a cause of FH
Linkage study - analysis of monogenic disorders
Association study - analysis of complex disorders/phenotype
- association between specific genetic variation and disease
Genome-Wide Association Study
GWAS of seven common diseases
Replication and Meta-analysis
Genetic loci identified with GWAS – March 2010
Alternative applications GWAS: quantitative parameters
Close-up of relationship with LDL-C in LDLR region
Example of a locus with a secondary joint association signal
conditioning on a primary signal
Mapping of the 19p12 genetic locus identified by
GWAS of plasma TG concentration
Identification of TM6SF2 as
putative functional
gene/protein in the
chromosome 19p12 locus
associated with plasma TG
concentration