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

Aberdeen

Dundee

Glasgow Edinburgh

Clinical Research Network

www.nesc.ac.uk/

www.abdn.ac.uk/ www.dundee.ac.uk/

www.show.scot.nhs.uk/www.mrc.ac.uk/

www.gla.ac.uk/www.ed.ac.uk/

Generation Scotland is supported by:

Founder Partners & Scientific Management Committee

SEHD Chief Scientists Office

Governance

Advisory Board

Management Committee

21CGH & 3DFuture

Directions

Implementation

Group

Informatics

PublicInvolvement

NHS ClinicalGenetics

LaboratoryIntegration

Communications

& PR

Exemplar Projects

Mental Health: Schizophrenia1,000 cases & controls: Edinburgh

(Blackwood & Muir) & Aberdeen (StClair)Osteoarthritis & osteoporosisPharmacogenetics

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 SignallingScience, 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: Height, weight, waist-hip ratio Blood Pressure x 2, resting pulse Spirometry and FEV1 Ankle brachial pressure index (ABPI)

Cognitive Function & Mental health 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)

Blood sample

DNA archive

Personal data

Health records

GenotypeData storage & analysis

Statistics & Bioinformatics

OUTCOMESscreening

surveillance targeted

treatmentoptimised treatment

Recruitment of family based cases and controls

Integration of Health Informatics & Genomics

ISD

Clinical & Laboratory Studies@ WTCRF, Edinburgh

State-of-the art facilities

Genetics Core

t c t a c t c t c

t c t a a t c t c

Find altered gene sequence

in people who are ill or at risk

Develop Drug

Use gene test to diagnose & choose best treatment Work out

what the

gene does Personalised

Medicine

?