ferdinand van ’t hooft cardiovascular genetics and genomics group karolinska institutet,...
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![Page 1: Ferdinand van ’t Hooft Cardiovascular Genetics and Genomics Group Karolinska Institutet, Stockholm, Sweden Genome-Wide Association Study GWAS](https://reader036.vdocuments.mx/reader036/viewer/2022062304/56649d095503460f949dbeaa/html5/thumbnails/1.jpg)
Ferdinand van ’t HooftCardiovascular Genetics and Genomics Group
Karolinska Institutet, Stockholm, Sweden
Genome-Wide Association Study
GWAS
http://en.wikipedia.org/wiki/Genome-wide_association_study
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Human Genome
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Genetic variation
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Single Nucleotide polymorphism (SNP)
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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%
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Linkage disequilibrium
Selections of SNPs representative for LD-blocks in the genome
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Linkage study versus association study
Linkage study of a familial hypercholesterolemia (FH) family
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Identification of mutations in PCSK9 as a cause of FH
Linkage study - analysis of monogenic disordersAssociation study - analysis of complex disorders/phenotype- association between specific genetic variation and disease
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Genome-Wide Association Study
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GWAS of seven common diseases
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Replication and Meta-analysis
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Genetic loci identified with GWAS – March 2010
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Alternative applications GWAS: quantitative parameters
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Close-up of relationship with LDL-C in LDLR region
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Example of a locus with a secondary joint association signal conditioning on a primary signal
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Mapping of the 19p12 genetic locus identified by GWAS of plasma TG concentration
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Identification of TM6SF2 as putative functional gene/protein in the
chromosome 19p12 locus associated with plasma TG
concentration
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