1. Ferdinand van ’t Hooft Cardiovascular Genetics and Genomics Group Karolinska Institutet, Stockholm, Sweden Genome-Wide Association Study GWAS http://en.wikipedia.org/wiki/Genome-wide_association_study

2. Human Genome

3. Genetic variation

4. Single Nucleotide polymorphism (SNP)

5. 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%

6. Linkage disequilibrium Selections of SNPs representative for LD-blocks in the genome

7. Linkage study versus association study Linkage study of a familial hypercholesterolemia (FH) family

8. 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

9. Genome-Wide Association Study

10. GWAS of seven common diseases

11. Replication and Meta-analysis

12. Genetic loci identified with GWAS – March 2010

13. Alternative applications GWAS: quantitative parameters

14. Close-up of relationship with LDL-C in LDLR region

15. Example of a locus with a secondary joint association signal conditioning on a primary signal

16. Mapping of the 19p12 genetic locus identified by GWAS of plasma TG concentration

17. Identification of TM6SF2 as putative functional gene/protein in the chromosome 19p12 locus associated with plasma TG concentration