LifeGene a unique initiative for health

The Concept – a national study with global implications

• 500,000 participants: ”0-45 years” at baseline• Including children and “born into cohort”• Household based ascertainment

• Information collected at several occasions• Including biobanking• Including event driven collection• Using modern E-epidemiology

• Follows changes in lifestyle and symptoms

• A resource for all scientific disciplines, nationally and internationally

Sweden has unique prerequisites for leading biomedical research

• National health care system, universally available

• Personal registration number

• Scientifically motivated population

• Cutting edge biotechnology

• Biobanking

• Continuously updated population and health care registers

• Well characterized patient materials

Sweden has large cohort studies: what is missing?

• Studies that bridge basic research to clinical applications

>> Particularly applicable to populations

• Sample collections that can be used for full scale of “omics”

• Truly prospective materials with information in advance of diagnosis

• Interest in co-morbidity

• Availability as a resource from the start

What more is missing?

• Disorders with early onset: in adolescence and young adulthood

• Disorders that cost society

>> Due to sick leave, etc

• Disorders which lead to chronic diseases late in life such as cardiovascular disease

• Psychiatric disorders, e.g., spectrum disorders, stress related diseases and gambling

• Infections, e.g., susceptibility to influenza

• Inflammation related disorders

• Musculoskeletal diseases, e.g., back pain, chronic pain

• Obesity

Sufficient Ns for power!

LifeGene 500 000 Yes No 0-45 Yes Yes Yes

UK Biobank 500 000 No No 40+ No No No

Millenium 500 000 No Yes 40+ No No No

deCode 150 000 No Yes 40+ No No No

Vanderbildt 150 000 No No 40+ No No No

Kadoorie Study

500 000 No No 40+ No No No

LifeLines 165 000 Yes No 20+ Yes No No

Conor/HUNT 200 000 No No 40+ No No Yes

Cohort studies 200 000 No No 40+ No No No

Number of participants

Diseases early

& middle of life

Diagnosis based recruitment

Age of participants

Household based

recruitmentEvent driven data collection

Born into cohort

LifeGene has unique features compared to other large longitudinal cohorts Unique

set up

LifeGene is both a cohort and an infrastructure

Cohort• Index persons 18-45 years

(random sample)

• Adult members of the household

• Their children (1/2 of the households)

• Twins as index persons

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Infrastructure

• High throughput biobanking

• In person testing centers

• IT and data management system

Biobanking

Physical testsBlood and urine sampling

In Person Testing Centers

IT and data management

Many studies will benefit from LifeGene’s infrastructure

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Support center

LifeGene will use a variety of sources for data collection

• Biological samples• Physical

measurements• Questionnaires

–Regular–Events

• Etc

External registers with individual data

• Central research registers, e.g. Patientregistret

• Primary care records• Etc

Participants

External registers with environmental data• Pollution• Noise• Weather• Etc

Evaluation criteria for data collection

• Scientific value• Validity• Feasibility• Cost

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LifeGene will enable –omics studiesthrough standardized, state of the art sampling

Omics Description

Genomics Analysis of human genes

Epigenomics DNA and histone-protein modifications by environment

Transcriptomics mRNA expression related to environment and diseases

Proteomics Protein expression and modifications related to diseases

Metabolomics Low molecular weight substances related to diseases

Toxicomics/Trace Metals

Toxic substances and trace metals detectable in plasma

Cellomics Characteristics and functions of living cells related to diseases

LifeGene will allow event based studies – Example Influenza-like illnesses (ILI)

Sep Oct Nov Dec Jan Feb Mar Apr

Outbreak Season starts

Event reporting

• Internet•Call-center•Symptom questionnaire

End of season

)

) )

Self-test

•Nasal swab

Analysis

•Test for real influenza

Nurse visit

•Serum•PBMC•Nasal swab•Symptom questionnaire

•All household members

Before sampling

• N = 1000• PBMC• Part of IPT routine

After sampling

• N = 1000• PBMC• Collection TBD

8-12 days

For real influenza cases

Some specifics

20080111 LifeGene work

meeting

Sampling during pilot – start Oct 7, 2009

Main sampling

• N=5,500 completed

• Random selection based on age, gender and geography

• Household-based– Invite partner (100%)– Invite children (100%)

• Geography: Stockholm (4,000), Umeå (1,000), Alingsås (500)

Event driven follow-up

Pregnant/born-into-cohort• N ≈ 100

Influenza like illnesses (ILI)• N = 1000+ before pilot• Complement with pilotLifeGene

pilot cohort

Spontaneous sign-up

• Spontaneous recruitment allowed

• Potential through ILI-E

All participants will answer a baseline questionnaire

Theme

Socio-demography

Lifestyle

Menstruation and reproduction

Tobacco, alcohol and drugs

Self-care

Medical history

Inflammation and allergy

Injuries

Mental health

# questions

30-77

191-298

25-46

9-45

4-60

49-227

18-65

1-18

105-455

Modules

General, Occupation, Working environment

General, Diet, Physical activity, Sexual behavior, Wireless devices

Menstruation, Reproduction, Menopause, Diseases, Osteoporosis

Smoking, Snus, Alcohol, Illicit drugs

Medication Over The Counter, Complementary and Alternative Medicine

Dental, Diseases, Infectious Diseases, Eating disorder, Reflux/IBS, Sleep, Headache, HearingGeneral exposures, Asthma & COPD, Allergy and chronic sinusitis

One module

Personality test, Screener, Depression, Panic disorder, Obsessive Compulsive Disorder, Post Traumatic Stress Disorder, Social phobia

Baseline Questionnaire overview (adults)

Sum 432-1291

Baseline Questionnaire overview (children / parents)

Theme

Socio-demography

Lifestyle

Puberty, menstruation and reproduction

Tobacco, alcohol and drugs

Self-care

Medical history

Inflammation and allergy

Injuries

Mental health

# questions

3-5

21-181

5-42

1-123

4-60

10-87

15-65

1-18

73-455

Modules

Household structure

Daycare and school, Diet, Physical activity, Washing, Sexual behavior, Wireless devices, Sun

Puberty, Menstruation & Reproduction

Smoking, Snus, Alcohol, Illicit drugs

Medication Over The Counter, Complementary and Alternative Medicine

Dental, Diseases, Vaccination, Eating disorder, Sleep, Headache, Hearing

Asthma, Allergy and chronic sinusitis, Pet exposure, Eczema

One module

Development and well-being, Infant behavior, Family environment, Parenting

Sum 133-1036

Data will be collected at baseline and then yearly

QFBorn into

cohort

1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

16

17

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18

IB IF IF (IF) IF IF IF IF IF

QF QF QF QF QF QF QF QF QF QF QF QF QF QF QF QF QFQB

QF

I

Q

QB QF+IB QF QF QF QF QF QF QF QF QF QF QFQF+IF QF+IF

QB+IB QF QF QF QF QF QF QF QF QF QF QFQF+IF QF+IF

QB+IB QF QF QF QF QF QF QF QF QF QFQF+IF QF+IF

QB+IB QF QF QF QF QF QF QF QF QFQF+IF QF+IF

QB+IB QF QF QF QF QF QF QF QFQF+IF QF+IF

QB+IB QF QF QF QF QF QF QFQF+IF QF+IF

QF QF QF QF QF QF QFQF+IF QF+IF

QF QF QF QF QF QF QFQF+IF QF+IF

QF QF QF QF QF QF QFQF+IF QF+IF

QF QF QF QF QF QF QFQB+IB QF+IF

QB+IB QF QF QF QF QF QFQF+IB

QB+IB QF QF QF QF QFQF+IB

QB+IB QF QF QF QFQF+IB

QF QF QF QFQB+IB

QB QF QF QF+IB

QB QF QF+IB

QB QF+IB

Age of recruitment

18- QB+IB

. . .

IF every 5 yearsQF every year

Age of data collection

QF

QB+IB

QB+IB

QB+IB

Infant

Pre-school kid

School kid

Teenager

Adult

parents answer

questionnare

Yes

Yes

Yes

No

No

QB: Questionnaire, baseline

QF: Questionnaire, follow-up

IB: In person test, baseline

IF: In person test, follow-up

Legend

At IPT LifeGene participants will conduct physical measures

Physical measures

Audiometry

Height

Bio-impedance

Weight

Hip circumference

Waist circumference

PEF (Peak Expiratory Flow)

Blood pressure

Heart rate

Blood and urine will be collected – to enable “omics”genomics, proteonomics, etc.

1 EDTA Whole blood 4ml

1 Li-Hep with Gel plug 8ml

1 Citrate 3.8%, 4ml

1 Li-Hep with gel plug 8ml

1 EDTA whole blood 4ml

2 EDTA 9ml

1 Urine 9ml

IPT sampling

= 9

WBC + diff

Frontend chem.

2+2 tubes, 0.3ml 2 tube, 0.3ml

6 tubes, 0.3ml 2 tubes, 0.3ml

3 tubes, 0.3ml 1 tube, 0.3ml

14 tubes, 0.3ml 2 tubes, 0.3ml

6 tubes, 0.3ml 2 tubes, 0.3ml

Main Storage

= 39

Backup Storage

= 11

DNA extr. + aliquoting

Aliquoting plasma

Aliquoting plasma

Aliquoting plasma

Aliquoting

Processing

1 Trace metal tube 7ml Aliquoting plasma 6 tubes, 0.3ml 2 tubes, 0.3ml

Front-end chemistry will be undertaken

Analysis Tube Machine Comment

WBC+diff EDTA Hematology

HBA1c EDTA Frontend chem

ALAT&GT Li-Hep Frontend chem

CRP Li-Hep Frontend chem

Cystatin C, kreatinine Li-Hep Frontend chem

Chol, ApoB, ApoAI, Tg Li-Hep Frontend chem

Potassium, Calcium Li-Hep Frontend chem

Albumin, glucose Li-Hep Frontend chem

X TSH Li-Hep Immuno system Needs sep. 1Mkr machine

X PSA Li-Hep Immuno system -”- ; low incid. in study pop

X Antitrypsin Li-Hep Frontend chem Low incidence of cirrhosis

X Ferritin Li-Hep Immuno system Needs sep. 1Mkr machine

X Ceruloplasmin Li-Hep Frontend chem Low incidence Mb WIlson

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Ethics Policy document

Example of content

• Relationship participants, scientists, 3rd parties

• Governance and relationship with society

• Funding, benefit sharing,

• IP and Access policies

Example of content regarding relationship to participants[…]For LifeGene, the rights and wellbeing of the participants prevail over the research interest of LifeGene and its users.[…]Because it will be impossible to anticipate all future research uses, consent will be sought for research in general that is consistent with LifeGene’s stated purpose, rather than for specific research.[…]

30+ pages

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The timeline is geared for an industrial scale roll-out in 2010

Prepare for pilot Conduct and evaluate pilot

Broad implementation

Collect and analyze data from 5,000 participants

2008 2009 2010 2011 2012 2013 2014 2015

Collect and analyze data from 500,000 participants

2016

LifeGene: a truly national project

Representatives from all Swedish medical faculties participate in LifeGene National Scientific Board

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