Metabolically Normal Obesity Study (MENOS)
Obesity is frequently associated with metabolic abnormalities (dyslipidaemia, raised glucose levels,
raised blood pressure) that are risk factors for cardiovascular disease and diabetes. However a subgroup of obese
individuals exists ('Metabolically Normal Obese' or MENO) who do not develop these disorders. It is unclear why this
subgroup of individuals remains metabolically healthy. To address this 20 MENO and 20 obese women with at least one
metabolic abnormality (mean BMI 42kg/m2) were recruited.
Three main hypotheses are being examined:
Contact for further information: louise.hayes@ncl.ac.uk
The North Cumbria Community Genetic Project (NCCGP) was established in 1996 when it began to collect samples of cord blood from over 85% of babies born at the West Cumberland Hospital, Whitehaven, Cumbria. Maternal blood samples were subsequently added to the collection and when recruitment ceased in 2003, over 7,000 neonates and 3,000 mothers had been added to the collection. The NCCGP is an ongoing project which has biological samples available for genetic epidemiological investigations. Demographic and birth details are also held. This resource has been used by a wide range of collaborators for a variety of scientific investigations.
Illustrative references:
- Healey CS, Dunning AM, Teare DM, Chase D, Parker L, Burn J, Chang-Claude J, Mannermaa A, Kataja V, Huntsman D,
Pharoah PDP, Luben RN, Easton DF, Ponder BAJ. A common variant in BRCA2 is associated with both breast cancer risk and
pre-natal viability. Nature Genetics 2000; 26: 362-364.
- Relton CL, Daniel CP, Hammal DM, Parker L, Tawn EJ, Burn J. DNA repair gene polymorphisms, pre-natal factors and the
frequency of somatic mutations in the glycophorin-A gene among healthy newborns. Mutation Research 2004; 545:
49-57.
Contact for further information: c.l.relton@ncl.ac.uk
Genetic susceptibility to preterm birth
The aetiology of preterm birth is poorly understood and evidence supports a role for genetic factors. The aim of this
project is to conduct the most comprehensive genetic association study of preterm birth to date. This is a collaborative project with Dr Tim Frayling and Professor Andrew Hattersley of Peninsula Medical School, Professor George Davey Smith of Bristol University and Dr Ron Gray of Oxford University, which is applying Illumina technoilogy to identify important genetic polymorphisms, both maternal and fetal, involved in preterm birth.
Illustrative references:
- Pennell CE, Jacobsson B, Williams SM, Buus RM, Muglia LJ, Dolan SM, Morken N-H, Ozcelik H, Lye SJ, PREBIC Genetics
Working Group, Relton CL. Genetic epidemiological studies of preterm birth: Guidelines for research. American
Journal of Obstetrics & Gynecology 2006 May [Epub ahead of print].
Contact for further information: c.l.relton@ncl.ac.uk
Further work is being conducted to define genetic determinants of low birth weight. The NCCGP resource is being used to study a range of genetic variants which are postulated to impact upon fetal growth. On-going studies include the analysis of metabolic polymorphisms, maternal smoking habits and birth weight. Collaborators at the Peninsula Medical School are studying the influence of genetic variants in glucose and fat metabolism on birth weight.
Illustrative references:
- Relton CL, Pearce MS, Burn J, Parker L. An investigation of folate-related genetic factors in the determination of birth
weight. Paediatric Perinatal Epidemiology 2005; 19: 360-367.
Contact for further information: c.l.relton@ncl.ac.uk
An investigation of genetic variation in epigenetic modification is funded by an EU 6th Framework Network of Excellence in Nutrigenomics (PI Prof John Mathers) to look at genetic variation in DNA methyltransferase enzymes and relating this to DNA methylation status in a cohort of mothers and their neonates. This is in the context of a larger study into epigenetic mechanisms underlying the phenomenon of developmental programming.
Contact for further information: c.l.relton@ncl.ac.uk
The Gateshead Millennium Study DNA Bank is a longitudinal cohort which aims to study the early origins of obesity (PI Dr Ashley Adamson). A collection of saliva samples is underway to establish a biobank of DNA from these children in order to investigate biological mechanisms underlying appetite regulation. In particular we are interested in studying the role of epigenetic mechanisms in appetite regulation and early influences on body composition.
Contact for further information: c.l.relton@ncl.ac.uk
A study of genetic susceptibility to childhood atopic eczema is in progress. This is the focus of an MD project for Dr Sara Brown and aims to investigate the role of genetic variation in the filaggrin gene in childhood atopic eczema using the North Cumbria Community Genetics Project cohort.
Contact for further information: sara.brown@ncl.ac.uk
The People of the British Isles project aims to construct a genetic map of the UK by asking volunteers who can trace their grandparents back to the same geographical location to provide a blood (DNA) sample. The project is lead by Professor Sir Walter Bodmer (Oxford University) with local involvement as a collaborator recruiting volunteers across the North East and Cumbria. DNA will be analysed for over 2000 ancestrally informative markers and the final population will ultimately provide a UK control population that can be adjusted for genetic diversity in disease-based genetic association studies.
contact for further information: c.l.relton@ncl.ac.uk
Study website: http://www.peopleofthebritishisles.org
The Newcastle Heart Project consisted of sequential cross sectional studies which compared the prevalence of diabetes, cardiovascular disease and associated risk factors in people of Chinese, European and South Asian origin resident in Newcastle upon Tyne. It illustrated the complexity of ethnic group differences, which defy simple explanations, and formed the basis for much subsequent aetiological and preventive work. It received funding from the Barclay Trust, Department of Health and local Hospital Trustees.
Illustrative references:
- Unwin N, Harland J, White M, Bhopal R, Winocour P, Stephenson P, Watson W, Turner C, Alberti KG: Body mass index,
waist circumference, waist-hip ratio, and glucose intolerance in Chinese and Europid adults in Newcastle, UK.
Journal of Epidemiology & Community Health 1997, 51(2):160-166
- Bhopal R, Unwin N, White M, Yallop J, Walker L, Alberti KG, Harland J, Patel S, Ahmad N, Turner C et al: Heterogeneity
of coronary heart disease risk factors in Indian, Pakistani, Bangladeshi, and European origin populations: cross
sectional study. British Medical Journal 1999, 319(7204):215-220
Contact for further information: n.c.unwin@ncl.ac.uk
Newcastle Thousand Families Study
The Thousand Families Study began when all 1142 babies born in Newcastle in May and June 1947 were
recruited into one of the first ever longitudinal cohort studies. The nature of research in the study
evolves as the cohort age, but most recent research has concentrated on lifecourse predictors of a number of adult
health outcomes, including cardiovascular, metabolic, oral, musculo-skeletal and mental health and breast tissue
density.
Contact for further information: m.s.pearce@ncl.ac.uk
Infections have been suggested to play a role in the aetiology of Type 1 diabetes. The presence of
space-time clustering is consistent with a possible environmental component to disease aetiology, possibly linked to
infections.
We tested for evidence of space-time clustering among children and young adults aged 0-29 years, using data from a
population-based register in Yorkshire, UK. There was statistically significant space-time clustering that was limited
to young people aged 10-19 years. This finding is consistent with an aetiology involving late exposure to infection.
Illustrative references:
- McNally R.J.Q, Feltbower R.G, Parker L Bodansky H.J, Campbell F, McKinney P.A. Space-time clustering of type 1
diabetes amongst 0-29 year olds in Yorkshire, UK. Diabetologia 2006, 49:900-904
Contact for further information: richard.mcnally@ncl.ac.uk
A register of the incidence of Type 1 diabetes mellitus in 0-15 year olds from the Yorkshire region of the UK was set up and was used for epidemiological and statistical analyses. Incidence was comparable to other areas of the UK: there was an upward trend in incidence of 1.75% per annum, but with a marked epidemic pattern with peaks at 4-year intervals. Incidence peaks occurred in early childhood at time of puberty, and there as substantial seasonal variation in incidence. An econological analysis found that incidence was associated with environmental factors including population density and overcrowded homes. This latter finding suggested that infections may be involved in aetiology.
Illustrative references:
- Staines A, Bodansky HJ, McKinney PA, Alexander FE, McNally RJQ, Law GR, Lilley HEB, Stephenson C, Cartwright RA. Small
area variation in the incidence of childhood insulin-dependent diabetes mellitus in Yorkshire, UK: Links with overcrowding
and population density. International Journal of Epidemiology 1997, 26:1307-1313
- Staines A, Bodansky HJ, Lilley HEB, Stephenson C, McNally RJQ, Cartwright RA. The epidemiology of diabetes mellitus
in the United Kingdom: The Yorkshire Regional Childhood Diabetes Register. Diabetologia 1993, 36:1282-1287
Contact for further information: richard.mcnally@ncl.ac.uk