Page 90 - ESHRE2019

‘Single-gene’ vs. Complex diseases
Single-gene (‘Mendelian’)
• Caused by single, rare, mutations that confer a very high risk
• Disease primarily identified in families
• Examples: Huntingdon’s chorea; Cystic fibrosis
• Typical study design: Family-based Linkage Studies
Complex
• Caused by multiple genetic variants + environmental factors, each
carrying small increases in risk
• Disease observed in families as well as sporadic cases
• Examples: Cancers, CVD, Type I/II Diabetes, Endometriosis.......
• Typical study design: Genome-wide Association Studies (GWAS)
NB Sub-types of complex diseases can behave as Mendelian traits,
e.g. Familial breast and ovarian cancer caused by BRCA1/2 mutations.....
Genome-wide Association Study (GWAS)
Test difference in frequencies of SNPs across the whole genome, between cases and controls
Cases Controls
Per chromosome: SNP variant
A
G Chromosome pair:
SNP genotype
AA AG GG
0.17 0.83
0.03 0.28 0.69
0.15 0.85
0.03 0.24 0.73
• Statistical tests • SNP-based risk
estimates
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