EpiScania Symposium
Medicon Village, Lund
2nd September 2015
The birth of the population-based cohort
studies in preventive medicine
From Framingham to Värmland
Peter M Nilsson, MD, PhD
Department of Clinical Sciences
Lund University
University Hospital, Malmö
Sweden
Framingham Heart Study - since 1948
First headquarters
Screening in three generations
Framingham Heart Study
Started in 1948
Offspring Study in 1971
Third generation in 2002
FHS – generation 1: n= 5209
FHS - generation 2: n= 5124
FHS – generation 3: n= 4095 (2005)
”Framingham Offspring Study” >350 publications
Focus on cardiovaskular risk, genetics and biomarkers
Gunnar Jungner 1914 – 1982
Swedish engineer, visited the US in 1950´ies
Mobile x-ray screening for tuberculosis
X-ray device
Bus for screening 1955
Bror Rexhed
1914 – 2002
Director ”Medicinalstyrelsen”
Tage Erlander
1901 - 1985
Swedish Prime Minister
The Värmland Health Survey
• Sweden´s first large population-based screening study
was carried out in the county of Värmland by initiative of
”Medicinalstyrelsen” during 1962 to 1965
• In total, 97,000 subjects came to the health screening
(76% of all invited)
• Simple physical examination done. Blood samples sent
on the night-train from Karlstad to Stockholm for further
analyses in the new multi-analysator (Ingmar Jungner)
• Follow-up after 20 years (Gunnar Lindberg, LU, Sven
Törnberg, KI), and 40 years (Payam Khalili, ÖU)
Development of new technologies for large screening studies during 1960´ies
Device for automatic blood analysis.
Värmland Health Survey 1962
Ingmar Junger, Lab, Stockholm
Device for analog-digital transformation, as well as automatic
Evaluation and statistics. Värmland Health Survey 1962
”Men born in 1913”
Gösta Tibblin
1929-1997
Göteborg
Tibblin G. High blood pressure in men aged 50
- a population study of men born in 1913.
Acta Med Scand (Suppl.) 1967;470:1-84.
Uppsala Longitudinal Study of Adult Men
(ULSAM), n= 2300
Bertil Hood
1917-1991
Malmö Preventive Project (MPP), n= 33,000
Berglund G, Nilsson P, Eriksson KF, Nilsson JA, Hedblad B, Kristenson H,
Lindgärde F. Long-term outcome of the Malmö preventive project: mortality
and cardiovascular morbidity. J Intern Med. 2000 Jan;247(1):19-29.
The Malmö Preventive Project (MPP)
Age-cohorts at baseline screening in the MPP cohort
Women
Age
Men
Age
Baseline screening in 1974-1992, included 22,000 middle-aged men
and 11,000 women (attendance rate 72%).
Follow-up in national registers is possible for 25-30 years in most subjects.
Berglund G, et al. 1996, 2001, Nilsson P, et al. 2002, 2003, 2004
MGR
FOB: Folk- och Bostadsräkningen (Population censuses, for social data)
MGR: Multi-generational Register (for finding first-degree relatives)
PKU Register and Biobank
Started in 1975, kept at Karolinska Hospital, Stockholm
Discovery of Legionella bacteria in 1977
Biobanking Work Processes
deCODE Genetics Inc. - Iceland
Kári Stéfansson
deCODE Genetics Inc. was founded in 1996 to identify human
genes associated with common diseases using population studies,
and apply the knowledge gained to guide the development of
candidate drugs
In December 2012, deCODE Genetics was purchased by Amgen
Biobanking past, present and future: responsibilities and benefits
University of California, San Francisco AIDS Specimen Bank - Deposits and
Withdrawals December 1982-August 2012.
De Souza YG, et al. AIDS. 2013;27:303-12.
UK Biobank Prospective Cohort
• 500,000 UK men and women aged 40-69 years
when recruited and assessed during 2006-2010
• Extensive baseline questions and measurements,
with stored biological samples (and opportunities
to add enhanced assessments in large subsets)
• Repeat assessments over time in subsets of the
participants to allow for sources of variation
• General consent for follow-up through all health
records and for all types of health research
• Sufficiently large numbers of people developing
different conditions to assess causes reliably
Locations of
UK Biobank
assessment
centres around
the UK (with
people recruited
from urban and
rural areas)
UK Biobank: 500,000 participants
aged 40-69 recruited in 2007-10
Age
Gender
Deprivation
40-49
119,000
50-59
168,000
60-69
213,000
Male
228,000
Female
270,000
More
92,000
Average
166,000
Less
241,000
Generalisability (not representativeness): Heterogeneity of study
population allows associations with disease to be studied reliably
Newer Swedish population-based
studies with associated biobanks
• Lifegene (KI)
0-45 years
• EpiHealth cohort (UU, LU)
45-75 years
• SCAPIS (HLF)
CV, lung
• Malmö Offspring Study (LU)
Family patterns
• BIG-3 (RS)
Smoking and risk
Microbiota and
its consequences
for health
-
Metabolism
Obesity
Immunology
Vascular function
A link to early life
colonization of the GI
tract of newborns
during delivery
Tremaroli, Bäckhed
Nature 2012; 489:242–249
Summary
 The first large-scale population-based screening study was the
Framingham Heart Study (FHS), started in 1948
 In Sweden, the Värmland Health Survey in 1962 and the “Men born
in 1913” in 1963 were two of the first large epidemiological studies
 The first biobanks added to large studies was the Malmö
Preventive Project 1974-1992 and the ULSAM study in Uppsala
 New technologies, registers for follow-up and a high attendance
rate were important aspects of the early studies in Sweden
 The PKU register was an early national biobank initiative (1975)
PN 2015