Availability of cohorts and quality issues

Cohorts: A goldmine for research

Eva Ortega-Paíno, PhD

Research and National Biobank Sample Coordinator

Biobank in Sweden

Lund University

Region Skåne Biobank BD47 (Laboratory Medicine)

e-mail: eva.ortega-paino@med.lu.se/ eva.ortegapaino@skane.se

Image: http://www.strengthvillain.com/your-personal-gold-mine/

What is a cohort?

Cohors: Roman legions were composed of 10

cohorts (worriors and commanding

centurions) that were traceable

Epidemeology: Group of people with defined

characteristics who are followed up to determine incidence

of, or mortality from, some specific disease, all causes of

death, or some other outcome.

Cohorts as Observational Studies

Evaluation of associations between diseases and exposures

Temporal

dimenssion

Retrospective Prospective

Three arguments for population-based cohorts with biobanks

• To understand the transition from health to disease manifestations

• To map causal pathways by use of modern genetics and register-based follow up (Mendelian randomisation) = future drug targets

• To use modern biobanks for advanced phenotyping (genetics, omics, biomarkers, etc.), useful for prediction of risk

Malmö Preventive Project (Malmö Förebyggande

Medicin – MFM )

Malmö Diet and Cancer Study (Malmö Kost

Cancer Studien – MKC)

Malmö Offspring Study (www.med.lu.se/mos)

EpiHealth (www.epihealth.se/)

Some examples of cohort-studies in our

Region

https://www.how-to-draw-funny-cartoons.com/

22000 11000

400 5700 50 1200

6700 11500

• The MPP started in the early 70’s

• Screening survey in the middle-aged population of

Malmö (32-51 years)

• Subjects born in Malmö

• Clinical examination, questionnaire and blood

sampling.

• 22,444 men and 10,902 women (1974-1992)

• During a later follow-up, the MPP-Re-examination

(MPP-RES) in all 17,284 of the original screenes

attended in 2002-2006.

Quality issue: Samples were stored at -20 C until

re-examination (-80C)

The Malmö Preventive Project

Population-based study to assess morbity

and mortality on cardiovascular diseases

17000 11000 1300 1050

13500 2600

2200 150013600 8800

• 30,000 subjects examined in 1991-1996, of which 28,000 subjects had full data set (diet) – EPIC cohort¨

• Age 44-74

• Physical exam, questionnaire, dietary registration

• Biobank samples, DNA

• Genetics: GWAS, exome sequencing in all (Regeneron Inc. US)

• Register follow-up for incident cardiometabolic and cancer events until 2016-12-31

https://www.how-to-draw-funny-cartoons.com/

Malmö diet and cancer study

Population-based proospective cohort to study the impact of diet on

cáncer incidence and mortality

• 6100 subjects examined in 1992-1996

• 3700 subjects (mean age 71 years, 2/3 women) examined during the MDC-CV re-exam in 2007-2012

• Pulse Wave Velocity (PWV) in 3050 subjects (SphygmoCor) –arterial stiffness

• Biobank samples, DNA, OGTT in non-DM subjects

• Genetics: GWAS, exome sequencing

• Register follow-up for incident events

Baseline

MDC-CV

• Ongoing since March 2013, planned until 2020

• Children and grand-children to index subjects(grandparents) in the MDC-CV cohort

• At present 3600 subjects screened for PWV (SphygmoCor), but also 24-h Arteriograph, 24-h ABPM

• Focus on phenotyping, genetics, diet, oral and GI microbiota patterns

• Additional vascular and metabolic phenotypes: carotidultrasound, EndoPat, AGE Reader (sf), biomarkers

Malmö Offspring study cohort

• Physical examination

• Questionnaire

• Lab-samples (with DNA extraction)

• Urinary- and feces sampling (microbiota)

• OGTT (in the beginning), changed to fasting samples

• Technical investigations (PWV, PWA, cIMT, EndoPat)

• Dietary registration (4-day)

• Cognitive testing

• Oral and dental investigations, oral microbiota in the Malmö Offspring Dental Study (MODS)

Microbiota and its consequences

for health- Metabolism

- Obesity

- Immunology

- Vascular function

The EpiHealth-Elderly cohortAim: 300,000 Swedish subjects aged 45-75 yearsInitially recruited in Uppsala and Lund/Malmö

Pilot Projects started in Uppsala in April 2011 and in Malmö in January 2012,currently 25000 subjects have been investigated in September 2019

IT-based medical history of diseases

and life-style factors

(Diseases, medications, diet, smoking,

social network, exersice, QoL,

occupational exposures)

First visit: Blood, urine, DNA,

Blood pressure, heart rythm,

Weight, height, waist

circumference, fat mass,

FEV1, cognition, ADL

Glucose and lipids

Secondary visits for selected

groups: CV, osteoporosis,

lung disorders, dementia etc

Invited groups:

1. Random sample

2. Parents and grandparents

to LifeGene participants

3. From old cohorts at UU/LU

4. From screening programs

Follow-up through registers:

Death, hospitalization, cancerBiobanking at KI Biobank

LifeGene

(18-45 years )

EpiHealth

(45-75 years)

Omics substudy

• GWAS chip in 2500

• Proteomics: CVDI & CVDII & Metabolism

• Metabolomics: Nightingale, MRS-based, 200 metabolites, focus on lipoprotein classes

Study of interactions between genotypes and

lifestyle factors

I would like to thank Peter Nilsson and Sölve Elmståhl for their kindness in providing information about the

Malmö cohorts

Questions arose for discussion

• Once we have all these cohorts and a huge amount of material and data

1. How to market all this material and make it available for research to

give it the right value and revert this value to the society?

2. What is the right forum?

3. Talking about quality, can we ensure quality from the first to last sample in

a long prospective study?

4. Are they far too expensive to conduct until the end of the

collection/study?

5. What about the follow up (long durations, difficulty to be mantained)?

ARE WE EXPLOITING THE GOLDMINE PROPERLY, or just getting

stones out of it?