Addressing the
Health and Wealth of Scotland
www.generationscotland.org
A vision for Scotland
with a global view
Generation Scotland aims to
 Establish an integrated research network between the Scottish Medical
Schools and NHS in Scotland, in collaboration with the National eScience
Centre and the MRC Human Genetics Unit in order to
 Recruit a prospective, intensively phenotyped family based cohort study (n =
50,000), recruited through primary care and linked through NHS health records,
around which we will
 Conduct an ongoing public consultation and engagement process to address
existing and evolving ethical, legal and social issues associated with the
research, which seeks to
 Identify genetic contributions to current and projected common causes of ill
health and related quantitative traits,
 By applying genomics, bioinformatics and systems biology to public health
 For the diagnosis, prognosis & prevention of ill health and
 As a platform for translational research, rational drug discovery & clinical trial.
Origins
Building the case & getting started
 2001: Scottish Enterprise support business scoping
 2002: Royal Society of Edinburgh Discussion Dinner endorses
plan
 2002: Programme of Public Consultation and Engagement
initiated by Innogen
 2003: SHEFC Strategic Research Development Grant awarded:
£1.97million for ‘Genetic Health in the 21st Century (21CGH)’
 2003: Scottish Executive Health Department announce
Genetics Healthcare Initiative
 2004: 21CGH consortium bid successfully for Scottish Family
Health Study (£4.4million award including £1million capital
equipment) (SFHS)
 2004: CSO support collection of SNBTS control samples (3D:
Donore BNA Database)
 2005: Joint development of 21CGH, 3D & SFHS under
Generation Scotland banner
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
GS: 21CGH
‘Genetic Health in the 21st Century’
Recruitment & training of genetics nurses
Recruitment of representative control
cohorts
500 each @ 4 urban & 2 rural areas of Scotland
Scottish grandparental origin
Genetic history & diversity
Core phenotyping for heart disease, metabolic
disease & mental health
Real time, electronic data capture & questionaire
DNA, plasma & peripheral blood lymphocytes for
cell lines
Building the statistical genetics, quantitative
genetics & epidemiology skill base
GS: 21CGH
‘Genetic Health in the 21st Century’
ELSI programme
Innogen (www.innogen.ac.uk) & AHRC
Research Centre for Studies in Intellectual
Property and Technology Law
Public consultation & engagement: early &
sustained
To work with, learn from and inform the public about
genetic health
Investigating issues of
Consent for current & prospective (outline) research
use
Data security & confidentiality
Ownership & use of genetic data
3D: Donor DNA Database
CSO funded Scottish National Blood
Transfusion Service sample collection
6,000 over 2 yrs, 4 regional centres, 3 age
bands.
Healthy donors, minimal genealogy &
phenotyping
Blood for DNA (genotyping) and serum
(proteomics, QTL)
Reference control set for bona fide users
Return of data to central, cumulative
database
Exemplar Projects
Mental Health: Schizophrenia
Osteoarthritis & osteoporosis
Pharmacogenetics
Optimised prescription, based upon
genetic profile
Avoidance of adverse drug reactions
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
Pre-clinic Questionnaire
 Demographic details, including family background
 Current drug history
 Personal and family medical history
 Rose angina questionnaire
 Musculoskeletal history
 Fractures
 Osteoarthritis
 Chronic pain
 Lifestyle
 Alcohol consumption
 Smoking history
 Educational and occupational history
Clinic Measures
 Physical measures:
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

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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)
Informatics
Co-ordinators
Ian Ford (Glasgow)
Mark MacGilchrist (Dundee)
Key Players
ISD (NHS Scotland)
Robertson Centre (Glasgow)
Health Informatics Centre (Dundee)
National eScience Centre (Glasgow/Edinburgh)
Data and samples
Unique study number allocated
No personal information available to study
team unless provided by participants
Personal information securely encrypted, deencryption only possible with 2 authorised
NHS permissions
Anonymised health data stored electronically
Anonymised DNA & genetic stored
separately
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
Health & Gene Data
Systematic collection & validation of
NHS routine health data
Laboratory studies: LIMS
Data provenance, acquisition,
management & security
Web & Grid based tools
Real time data capture & validation
Data integration, mining & analysis
Statistical & epidemiological testing
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
Bioinformatics Challenges
 Relating signs & symptoms (clinical
diagnosis and medical records) to the
molecular basis of disease (genetic tests)
 Optimising & Individualising treatment
 Pharmacogenetics & Pharmacogenomics
 Linking genomics to proteomics &
metabolomics
 Systems biology
 Moving from gene discovery to rational
drug design, development and clinical trial
Future Directions
 In the next five years we aim to have
 High fidelity phenotyping of disease and related quantitative
traits on a family-based cohort of 50,000
 Matched biological samples for hypothesis generation and
testing
 Research quality integration of routine NHS data
 Ongoing public support and involvement
 An internationally competitive research infrastructure
 Epidemiology, statistics & informatics
 Genetics & genomics
 Pharmacogenomics
 Systems biology
 Sustainable public & private sector support