Role of genetic association studies in drug
development
Felix A Kruger
Genetic Epidemiology Group
UCL Farr Institute
Genetic association data to inform the
discovery stages in drug development
Source: www.ebi.ac.uk/gwas
Genetic associations as proxies for drug
RCTs
0.06 mmol/L
per allele
https://www.google.com/doodles/
gregor-mendels-189th-birthday
courtesy Dan Swerdlow, UCL
Coverage of drug targets with current
genotyping platforms
See you soon!
UCL Genetic Epidemiology
UCL Clinical Epidemiology & Informatics
Aroon Hingorani
Chris Finan
Amand Floriaan Schmidt
Tina Shah
Jorgen Engmann
Tom Lumbers
Valerie Kuan
Juan-Pablo Casas
Pimphen “Penny” Charoen
The druggable genome
Publication
targets
Drews, 1997
485
Hopkins and Groom, 2002
399
Overington et al, 2006
324
ChEMBL, 2015
390
Drews, J. (2000). Drug Discovery: A
Historical Perspective. Science 287, 1960–
1964.
Hopkins, A.L., and Groom, C.R. (2002).
The druggable genome. Nature Reviews.
Drug Discovery 1, 727–730.
Overington, J.P.,et al(2006). How many
drug targets are there? Nature Reviews.
Drug Discovery 5, 993–996.
The druggable genome
Tier
#genes
description
1
1427
Drug targets + ADMET
2
682
Drug target related (50% seqId) or measured
interaction w/ cmpd
3a
870
Drug target related (25% seqId) or secreted/
extracellular protein + within 50kb of GWAS hit
3b
1500
Drug target related (25% seqId) or secreted/
extracellular protein
Integrating resources of GWAS and drug
target data
Gene
‫ݎ‬ଶ
GWAS
signal
LD relationship
variants
Genome-wide association studies
• Wellcome Trust Case Control Consortium
2007
• Genotyping with microarrays (~500k SNPs)
• Case control study design (> 2000, >3000)