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CLS
CLS
Cohort
Cohort
Studies
Studies
Newsletter
Newsletter
Autumn
Spring2007
2009
In this issue
• The British 1958 birth cohort DNA collection
• Using the Millennium Cohort Study to examine
growth and obesity across childhood
• Oral fluid collection in the Millennium Cohort Study
• Recent data deposits
www.cls.ioe.ac.uk
Following
lives from
birth and
through
the adult years
Special issue:
Biomedical
data
collection
The importance of biomedical data
collection within birth cohort studies
Peter Elias, ESRC Strategic Adviser (Data resources)
The articles in this special issue focus on the
collection of biomedical information
(specimens, measurements and questionnaire
responses) from members of the birth cohort
studies managed by the Centre for Longitudinal
Studies. David Strachan outlines the pioneering
work he and others undertook to create
immortalised cell cultures1 from members of
the 1958 birth cohort (see page 2), and
describes how this resource has played a major
role in case-control studies and contributed to
meta-analyses of the relationship between
genetic structures and biomedical traits. Lucy
Griffiths and Summer Hawkins (page 3)
describe research based on the Millennium
Cohort Study, linking measurements on infant
growth to maternal socio-economic status and
educational qualifications. They outline
methods used in current and past surveys to
collect measurements from cohort members
and their parents. Suzanne Bartington’s article
(page 4) discusses the procedures that were
adopted for collecting oral fluids from members
of the Millennium Cohort as part of a study of
the link between childhood infections and
allergies.
Underlying these examples are some broader
questions. How prevalent is a specific genetic
CLS
Measurements taken from Millennium
Cohort children have been used to
research the effects of maternal socioeconomic status and educational
qualifications on child growth
marker in the population and how does this
relate to cognitive and mental development?
Why do some children have healthier lifestyles
than others? Do families put their children at
risk of allergies by reducing their exposure to
infections? These are important questions that
require researchers from a variety of
disciplinary backgrounds to share ideas and
knowledge, and to avail themselves of the
richness of data provided by these national
Centre for Longitudinal Studies
Institute of Education, University of London,
20 Bedford Way, London, WC1H 0AL
tel: +44 (0)20 7612 6875 fax: +44 (0)20 7612 6880
email: [email protected] web: www.cls.ioe.ac.uk
longitudinal studies. These three short articles
are testimony to the need for high-quality
interdisciplinary research collaborations
between the medical and social sciences and
the need to sustain and develop further the
powerful data environment that the cohort
studies provide. In so doing, numerous barriers
must be broken down. Social scientists must
have at least a basic understanding of the
complexity of gene environment interactions.
Equally, medical scientists can benefit from
social research concepts and instruments, such
as those which measure socio-economic status
and poverty, and from social research findings,
particularly those drawing upon the fields of
social and educational psychology.
We have a long way to travel down this path,
but it will be rewarding in terms of the
additions to knowledge that such research will
bring. As the information provided by these
cohorts continues to grow, now covering
genetics, medical records and much personal
information about the lives of the cohort
members, the use of these resources for
research purposes requires vigilant
management and control. As David Strachan
points out, this is an issue that requires careful
attention. The guardians of the information and
their funders are currently seeking to put in
place appropriate data governance and
stewardship arrangements, thus ensuring that
the birth cohorts remain invaluable research
resources.
1) Immortalised cells continue to grow and divide indefinitely in
vitro for as long as the correct culture conditions are maintained.
The British 1958 birth
cohort DNA Collection
David Strachan, Professor of Epidemiology,
St George’s, University of London
Following the publication of a near-complete
map of the human genetic sequence at the turn
of the millennium, there has been an explosion
of interest in the use of genetic information in
studies of human health and disease. Rapid
advances in technologies for testing thousands
of DNA samples for multiple genetic variants
(mainly single nucleotide polymorphisms1 or
SNPs) have underpinned expansion of genetic
epidemiology on an industrial scale. Equally
important has been the assembly of large-scale
collections of DNA from population samples and
patients with specific diseases.
The British 1958 birth cohort (National Child
Development Study) has formed an important
part of this worldwide initiative. Between
September 2002 and March 2004, as part of a
Medical Research Council (MRC)-funded
biomedical survey, 9,377 cohort members were
visited by 120 trained nurses from the National
Centre for Social Research. They measured a
range of biomedical characteristics, such as
blood pressure and lung function, and also
collected blood samples from 88% of those
examined, of whom 97% gave consent to
extraction and storage of DNA for medical
research purposes.
The nationwide distribution of the cohort made it
particularly suitable as a basis on which to
develop a geographically representative panel of
DNA samples. In order to help produce large
quantities of high quality DNA, additional funding
was obtained from the Wellcome Trust for
creation of immortalised cell cultures. Pioneering
work by the Avon Longitudinal Study of Parents
and Children laboratory at the University of
Bristol allowed the automation of this cell-line
production by robots: a world first! The
biomedical survey provided 8,018 usable blood
samples from subjects who gave consent to
extraction of DNA, and 7,692 blood samples from
cohort members who also gave consent for the
creation of immortalised cell cultures. Successful
cell-line transformation was achieved for 7,526
(98%) of these, a remarkable achievement.
The resulting DNA collection, managed by the
Bristol laboratory, has been used, in whole or
in part, by over 30 collaborating groups, mainly
as a reference sample for case-control studies
2
The biomedical survey provided 7,692 blood samples from cohort members who
also gave consent for immortalised cell cultures.
of a specific disease. Use of the samples as
controls for the large Wellcome Trust CaseControl Consortium (WTCCC) and the
international Type 1 Diabetes Genetics
Consortium has generated data on at least half
a million SNPs on over 4,000 individuals. With
ongoing extensions to the WTCCC and other
studies, it is anticipated that such “genomewide”2 data on over 7,000 participants will be
available by the end of 2009.
As this huge amount of data has accumulated, it
has become apparent that no single study, even
of several thousand subjects, is sufficiently
powerful to detect with confidence the often
subtle effects of single SNPs on biomedical traits.
Alongside a systematic presentation of NCDSbased findings (http://www.b58cgene.sgul.ac.uk/),
results are now being contributed on a
collaborative basis to large-scale meta-analyses.
The emphasis in 2008 was on cardiovascular risk
factors, such as obesity, blood pressure,
cholesterol and blood clotting, while metaanalyses of lung function, asthma, allergy and
birthweight are planned for the first half of
2009. Increasingly, these meta-analyses are
coalescing into global “mega”-analyses
involving between 20,000 and 100,000 DNA
samples and about 2.5 million measured or
reliably imputed SNPs. The British 1958 cohort
data already comprise 4-20% of the material
(depending upon the trait under analysis). With
the projected increase in NCDS numbers with
genome-wide coverage, we anticipate
maintaining a similar position as the worldwide
resources expand over the next year or two.
These international consortia have operated
productively and efficiently on the basis of
exchange of results rather than individual-level
data. However, there is mounting pressure from
researchers in both biomedicine and the social
sciences for access to individually-linked genetic
and non-genetic data from the 1958 birth cohort
and similar studies. This poses special challenges
in relation to disclosure risks and compliance
with the informed consent obtained from
participants. Representatives of the major UK
funders (Economic and Social Research Council,
MRC and Wellcome Trust) are actively
considering these issues.
Further details of the British 1958 birth cohort
DNA collection, and on-line presentation of the
results (but not individual-level data) are
available at http://www.b58cgene.sgul.ac.uk/.
For details of the procedures for accessing DNA
samples and resulting genotypes, see
http://www.b58cgene.sgul.ac.uk/application.php
1) Natural variations in the DNA sequence.
2) A genome is the complete set of genes or genetic material
present in a cell or organism.
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Using the Millennium Cohort Study to
examine growth and obesity across childhood
Lucy Griffiths and Summer Sherburne
Hawkins, Medical Research Council (MRC)
Centre of Epidemiology for Child Health,
University College London Institute of Child
Health
Over the past two decades the proportion of
young children who are either overweight or
obese has increased substantially, presenting
one of the greatest threats to public health. This
has major implications in the short term for child
health, development and wellbeing, but also in
adulthood. Consequently, tackling childhood
obesity is a priority for the UK Government and
a long-term Public Service Agreement target has
been set to “reduce the proportion of
overweight and obese children to 2000 levels by
2020 in the context of tackling obesity across
the population”.1
It is therefore critical to understand more about
the mechanisms for the development of early
childhood obesity and how policies can influence
obesity and its determinants. The Millennium
Cohort Study (MCS) provides a unique
opportunity to do just that, given its nationallyrepresentative nature and the breadth of social
and health information held on children and
their families.
Body measurements have been made in the
MCS using trained interviewers and standard
protocols: child weight and height were
measured at ages three and five, and waist
circumference at five years. Furthermore,
maternal report of birthweight and weight at
nine months were obtained at the first interview.
Maternal and partner report of their own weight
and height has also been obtained at each
contact.
Here at the UCL Institute of Child Health, we
have analysed and published data from the first
two surveys, at ages nine months and three
years, with respect to infant growth as well as
individual-, family-, community-, and area-level
factors related to overweight and obesity in
three-year-old children2-8. Our research on the
MCS and the current evidence base suggests
that preventing overweight and obesity needs to
begin during pregnancy and early in life. At three
years, 18 per cent of children were overweight
and 5 per cent were obese using the
International Obesity Task Force cut-offs for body
30
25
20
20.9%
21.2%
23.5%
25.4%
England
Scotland
Wales
Northern
Ireland
15
10
5
0
Figure 1 Prevalence of overweight
(including obesity) at age five by
UK country
mass index9. We are currently analysing data
from the third survey. At age five, 16 per cent of
children were overweight and 5 per cent were
obese. However, the prevalence of overweight
(including obesity) varied significantly by UK
country, being lowest in England and highest in
Northern Ireland (Figure 1), similar to the pattern
seen at age three4. Analyses of sociodemographic risk factors for overweight and
obesity at age five suggest that girls were more
likely to be overweight or obese (23 per cent of
girls versus 19 per cent of boys), as were black10
children (36 per cent of black children versus 21
per cent of white children). Higher maternal
socio-economic status and educational
qualifications were associated with less risk of
overweight or obesity. In addition, children from
lower income households and lone parent
families were at increased risk of being
overweight or obese at age five11.
We are currently exploring the influence of
dietary and eating patterns, and children’s
activity levels, on overweight and obesity at age
five. Additionally, data collection for the fourth
contact, at age 7/8 years, will be completed in
spring 2009. This includes detailed
measurements of physical activity, using
movement monitors attached to children for
seven days, more dietary information and
additional assessments of the children’s body
composition, such as fat-free mass, using a
technique assessing electrical resistance
throughout the body.
References
1) HM Government. PSA Delivery Agreement 12: Improve the Health
and Wellbeing of Children and Young People. 2007. London, HMSO.
2) Griffiths et al, Differential parental weight and height
contributions to offspring birthweight and weight gain in infancy,
International Journal of Epidemiology, 2007; 36(1):104-7.
3) Tate et al., Is infant growth changing?, International Journal of
Obesity, 2006; 30(7):1094-6.
4) Hawkins et al., Regional differences in overweight: an effect of
people or place?, Archives of Disease in Childhood, 2008; 93:407-13.
5) Hawkins et al., An ecological systems approach to examining risk
factors for early childhood overweight: findings from the UK
Millennium Cohort Study, Journal of Epidemiology and Community
Health. Published online 18 Sep 2008; doi:
10.1136/jech.2008.077917.
6) Hawkins et al., Perceived and objective measures of the
neighbourhood environment and overweight in preschool children
and their mothers, International Journal of Pediatric Obesity.
Published online 15 Dec 2008; doi: 10.1080/17477160802596155.
7) Hawkins et al., Maternal employment and early childhood
overweight: findings from the UK Millennium Cohort Study,
International Journal of Obesity, 2008; (32):30-8.
8) Griffiths et al., Effects of infant feeding practice on weight gain
from birth to 3 years of age, Archives of Disease in Childhood.
Published online 19 Nov 2008, doi: 10.1136/adc.2008.137554.
9) Cole et al., Establishing a standard definition for child overweight
and obesity worldwide: International survey, British Medical Journal,
2000; 320:1240-3.
10) “Black” refers to Black African, Black Caribbean and Black
Other.
11) Unpublished data, in press.
Have you got news?
This newsletter about the British Cohort
Studies is produced for researchers,
policymakers, journalists and others who
are interested in longitudinal research.
Kohort provides information on the
current status of CLS cohort surveys and
data submission; coverage of research
carried out and papers published using
data from the cohorts; descriptions of
other cohort studies and networks;
updates on accessing data and
innovations around linkage and storage of
information, and other topics that relate to
cohort studies.
We always welcome submissions from outside
authors who wish to contribute to Kohort. So if
you work for another cohort study, have
published research relating to our cohorts, or
have other interests related to cohort studies, and
are interested in publishing an article in this
newsletter, please feel free to contact us. Kohort is
published three times a year and is a way of
informing others about matters of shared interest
in cohort studies.
Please contact Lorna Hardy at [email protected]
or on 020 7612 6861, to discuss any suggestions
you have about the content of Kohort.
3
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Oral fluid collection in the
Millennium Cohort Study
Suzanne Bartington, University College
London Institute of Child Health
There is evidence that the prevalence of
asthma and related conditions, such as forms
of rhinitis and eczema, has increased over
recent decades throughout the developed
world. The UK’s recent reviews of routine
health statistics, together with information
from national and regional surveys, suggest
that the incidence of diagnosed allergic rhinitis
and eczema has trebled over the past three
decades and that asthma in children has more
than doubled over the past 50 years. These
conditions are now a significant cause of ill
health in children and are of major public
health concern.
A range of explanatory theories for these
increases has been proposed, including, since
the late 1980s, the hygiene hypothesis. This
hypothesis proposes that a reduction in early
immune system stimulation, due to reduced
exposure to common childhood infections,
increases the risk of allergic disease in later
childhood. Evidence to support this hypothesis
has been provided by a number of studies, and
biologically plausible pathways have been
described. However, many epidemiological
studies have relied upon proxy measures of
infection exposure, including self-report, or
health service utilisation history, which have
limited value in children due to the
asymptomatic and non-specific nature of many
common infections.
The Millennium Cohort Study (MCS) provides a
unique opportunity to investigate the hygiene
hypothesis using an objective measure of
immune status to common childhood
infections, together with documentation on a
wide range of associated and confounding
factors. Blood serum has traditionally been the
sample of choice for measuring immune
status; however, taking samples by syringe
requires specially trained staff and sterile
equipment. Oral fluid provides an ideal
alternative, containing salivary components
and gum crevice fluid, which contains
antibodies, although at an approximately 10fold lower concentration than in blood serum.
Recent data deposits
Oral fluid is non-invasive, safe and may be
collected in the home, making it highly
suitable for collection in a large-scale child
cohort study.
NCDS biomedical data
The data from the biomedical survey of the
NCDS, when cohort members were aged 44–45
years, has just been released by the Data
Archive.
Families who were eligible for the second MCS
survey conducted when children were aged
three years, were posted a leaflet explaining
the purpose of oral fluid collection. Fieldwork
interviewers were trained in oral fluid
collection by video presentation and were
requested to perform the sample collection at
any time during the home interview. Samples
were sent to the Health Protection Agency,
where they were frozen before later testing for
antibodies to the Epstein-Barr Virus, VaricellaZoster Virus and Noro Virus, and total antibody
content as a marker of sample quality. Ethical
approval for sample collection was provided
by the London Multi-Centre Research Ethics
Committee1.
The survey was conducted, with several
collaborating partners, under the Medical
Research Council’s (MRC) ‘Health of the Public’
initiative. 12,037 subjects were contacted and
9,377 were successfully interviewed. The primary
objective was to obtain questionnaires, physical
measures and biospecimen collection (blood,
urine and saliva) and to use these to examine
how developmental, lifestyle, and environmental
factors act throughout the lifespan to influence
current ill health, and physiological and
psychological function in early middle age.
Oral fluid samples were received from 11,698
(81.4 per cent) of 14,373 singleton cohort
children with natural mothers as interview
respondents at the first and second survey,
over 90 per cent of which were suitable for
testing. Mothers of Black Caribbean ethnicity
or who lived in non-English-speaking
households were less likely to provide a
sample from their child. Mothers reporting a
history of asthma were, however, more likely
to return a sample.
Further details on the data collection are also
available from the CLS website:
www.cls.ioe.ac.uk/biomedical.
This was the first occasion upon which oral
fluid has been collected on a large scale from
pre-school-aged children and our findings
demonstrated that oral fluid is a highly
acceptable and feasible biological sample for
collection in a large-scale child cohort study.
Formal interpreter support may be required to
increase participation rates in surveys that
collect biological samples from ethnic minority
groups. It is hoped that this work will inform
future fieldwork for biomarker collection in
population-based and cohort studies.
1) Bartington SE, Peckham C, Brown D, Joshi H, Dezateux C.
Feasibility of collecting oral fluid samples in the home setting to
determine seroprevalence of infections in a large-scale cohort of
pre-school-aged children. Epidemiology and Infection.
2009;137(2)211-8
There have already been a number of
publications based on this data and these can be
found on our searchable bibliography at:
www.cls.ioe.ac.uk/publications.
BCS70 16-Year Arithmetic Test dataset
This dataset, known technically as the APU
Arithmetic Test, consisted of 60 questions,
included in the Student Test Booklet
administered in school under teacher
supervision. This information is now also
available from the UK Data Archive.
The data consist of the responses for each of the
60 test items for 3,677 cases, plus an additional
60 derived variables interpreting the answers
into ‘wrong’ or ‘right’, together with three
additional variables giving details of:
total score (number of correct items)
total number of incorrect items
● total number of items attempted.
●
●
More details are available on the CLS website
under BCS70 Current Activities,
www.cls.ioe.ac.uk/bcs70current.
The Guide to the 16-year Arithmetic Dataset
now appears in the BCS70 1986 section, under
Guides to the Datasets,
www.cls.ioe.ac.uk/bcs70guides.
Access to the UK Data Archive is at www.dataarchive.ac.uk
If you require this newsletter in a larger font size, please contact Lorna Hardy ([email protected])
ISSN 1747-6453 (PRINT)
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