Addressing the
Health and Wealth of Scotland
www.generationscotland.org
A vision for Scotland
with a global view
Generation Scotland aims to
 Prospective, intensively phenotyped family based
cohort study (n = 50,000), recruited through primary
care and linked through NHS health records
 Identify genetic contributions to current and
projected common causes of ill health and related
quantitative traits,
 Genomics, bioinformatics and systems biology to
public health
 Diagnosis, prognosis & prevention of ill health and
 Translational research, rational drug discovery &
clinical trial.
Our Competitive Advantage
 Scottish people & culture
 Unhealthy, Supportive & Stable Population
 Large scale family based studies possible
 NHS Scotland
 Disease Registers
 ‘Cradle to Grave’ Health Records
 Academic excellence
 Medical Genetic & Information technology
 Ethical, Legal, Social Sciences
Clinical Research Network
Aberdeen
Dundee
Glasgow
Edinburgh
Founder Partners & Scientific Management Committee
www.abdn.ac.uk/
www.mrc.ac.uk/
www.dundee.ac.uk/
www.show.scot.nhs.uk/
Generation Scotland is supported by:
SEHD
Chief
Scientists
Office
www.ed.ac.uk/
www.gla.ac.uk/
www.nesc.ac.uk/
Governance
Advisory Board
Future
Directions
Management
Committee
21CGH & 3D
NHS Clinical
Genetics
Implementation
Group
Laboratory
Integration
Public
Involvement
Informatics
Communications
& PR
Exemplar Projects
Mental Health: Schizophrenia
1,000 cases & controls: Edinburgh
(Blackwood & Muir) & Aberdeen (StClair)
Osteoarthritis & osteoporosis
Pharmacogenetics
Optimised prescription, based upon genetic
profile
Avoidance of adverse drug reactions
Major psychosis co-segregating with a
balanced t(1;11) translocation
St Clair et al Lancet (1990), Blackwood et al AmJHumGenet (2001)
major psychiatric illness (SCZ, BPAD, RMD)
minor psychiatric illness (ANX, ALC, MIND)
unaffected
t(1:11)
DISC1 and PDE4 Are Interacting
Genetic Factors in Schizophrenia
that Regulate cAMP Signalling
Science, 310, 1187-1191 (2005)
J. Kirsty Millar1, Benjamin S. Pickard1, Shaun Mackie1, Rachel James1, Sheila Christie1,
Sebastienne R. Buchanan1, M. Pat Malloy1, Jennifer E. Chubb1, Elaine Huston2, George S.
Baillie2, Elaine V. Hill2, Miles D. Houslay2, Nicholas J. Brandon3, Jean-Christophe Rain4, L.
Miguel Camargo3, Paul J. Whiting3, Douglas H.R. Blackwood1,5, Walter J. Muir1,5, David J.
Porteous1.
Science Magazine
‘Scientific Breakthroughs of the Year, 2005’
The DISC1-PDE4B
Pathway
A means towards
genetic stratification
& biomarker
discovery
A target for rational
drug development
Scottish Family Health Study
 50,000 family-based collection
 targeting sibships of 3+
 Phenotyping focus
 Cardiovascular disease
 Bone & joint disease
 Mental health
 Pharmacogenetics
 Questionaire, Clinical Exam & Follow up
 “high fidelity phenotyping”
 Quantitative Trait Analysis
 Systematic, electronic record linkage and follow up
Clinic Measures
 Physical measures:
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Height, weight, waist-hip ratio
Blood Pressure x 2, resting pulse
Spirometry and FEV1
Ankle brachial pressure index (ABPI)
 Cognitive Function & Mental health





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Eysenck Personality Questionnaire
Wechsler Memory Test (short- and long-term)
Digit Symbol test
Verbal Fluency
Mill Hill Vocabulary Scale
General Health Questionnaire-28
SCID Brief screening interview for major depression
 Blood: DNA, Lipid profile (cholesterol), urate, glucose
 Urine: Spot test; 24-hour collection (if possible)
Integration of Health Informatics
& Genomics
Recruitment of family based cases and controls
ISD
OUTCOMES
screening
surveillance
targeted
treatment
optimised
treatment
Blood sample
Personal
data
Health records
Data storage & analysis
Statistics & Bioinformatics Genotype
DNA archive
Clinical & Laboratory Studies
@ WTCRF, Edinburgh
 State-of-the art facilities
Genetics Core
Find altered gene sequence
in people who are ill or at risk
t c t a c t c t c
t c t a a t c t c
?
Personalised
Medicine
Use gene test to
diagnose & choose
best treatment
Work out
what the
gene does
Develop Drug