Generation Scotland

2006-2013

Research publications from 2006 - 2013

708 common and 2,010 rare DISC1 locus variants identified in 1,542 subjects: analysis for association with psychiatric disorder and cognitive traits. Thomson, P., Parla, J. S., McRae, A. F., Kramer, M., Ramakrishnan, K., Yao, J., … Porteous, D. J. (2013). Molecular Psychiatry, 19(6), 668–675.

DISC1 is a gene that has been shown to be causally linked to schizophrenia and recurrent , major depression when the gene is damaged by a chomosome rearrangement. This study looked to see if other types of more subtle damage to the DISC1 gene were seen in other cases. The answer was yes. Association with depression and with cognitive deficits were observed with novel variants in the coding and non-coding regions of DISC1.

 

Model Selection Approach Suggests Causal Association between 25-Hydroxyvitamin D and Colorectal Cancer. Zgaga, L., Agakov, F., Theodoratou, E., Farrington, S. M., Tenesa, A., Dunlop, M. G., … Campbell, H. (2013).  PLoS ONE, 8(5), e63475.

A lot of evidence points to a link between low levels of Vitamin D and increased risk of colon cancer, but the claims remain controversial as arguments are made about cause and effect and many possible confounders. The detailed information available for Generation Scotland participants helped control for many of the possible alternative explanations. The study favours a direct and causal link. 

 

Association between level of exposure to secondhand smoke and peripheral arterial disease: cross-sectional study of 5,686 never smokers. Lu, L., Mackay, D. F., Pell, J. P. (2013). Atherosclerosis, 229(2), 273-276.

The evidence for the harmful effects of smoking is beyond question, but what about the risks of passive smoking? Generation Scotland has sufficient data to demonstrate an effect of passive smoking on peripheral artery disease.

 

Cardiovascular risk factors associated with the metabolic syndrome are more prevalent in people reporting chronic pain: results from a cross sectional general population study. Goodson, N. J., Smith, B. H., Hocking, L. J., McGilchrist, M. M., Dominiczak, A. F., Morris, A., … Generation Scotland (2013). Pain (2013), 154, 1595-602.

Pain is a common feature of many illnesses. Here we show that although those reporting chronic pain did not have a significantly higher risk of heart disease, they did have an increased number of the risk factors often associated with heart disease, obesity and diabetes, such as raised blood glucose and increased body mass index.

 

Pedigree and genotyping quality analyses of over 10,000 DNA samples from the Generation Scotland: Scottish Family Health Study. Kerr, S. M., Campbell, A., Murphy, L., Hayward, C., Jackson, C., Wain, L. V., … Porteous, D. J. (2013). BMC Medical Genetics, 14, 38.

This paper provides the key information you need to know about the pedigree data and DNA quality in Generation Scotland.

 

Cohort Profile: Generation Scotland: Scottish Family Health Study (GS:SFHS). The study, its participants and their potential for genetic research on health and illness. Smith, B. H., Campbell, A., Linksted, P., Fitzpatrick, B., Jackson, C., Kerr, S. M., … Morris, A. D. (2012). International Journal of Epidemiology, 42(3), 689-700.

This is the second key reference to be used when citing Generation Scotland. It provides a comprehensive description of what we measured and how to collaborate with Generation Scotland in health related research.

 

Genetic variation in Hyperpolarization-activated cyclic nucleotide-gated channels and its relationship with neuroticism, cognition and risk of depression. McIntosh, A. M., Simen, A. A., Evans, K. L., Hall, J., MacIntyre, D. J., Blackwood, D., … Thomson, P. A. (2012). Frontiers in Genetics, 3, 116.

The HCN genes encode ion channels plausibly linked to psychiatric illness. Generation Scotland data was used to test for genetic association with DSM-IVdepression, neuroticism, and a battery of cognitive tests assessing cognitive ability, memory, verbal fluency, and psychomotor performance.  No association was found for any of the traits measured.

 

Heritability of chronic pain in 2195 extended families. Hocking, L. J., Generation Scotland, Morris, A. D., Dominiczak, A. F., Porteous, D. J., Smith, B. H. (2012). European Journal of Pain 16(7), 1053-1063.

Chronic pain is a feature of cancer and many lung, heart and joint diseases in later life. The family study design of Generation Scotland provides an estimate of 30% for the genetic (inherited) contribution to severe chronic pain. 

 

Alzheimer's disease risk factor complement receptor 1 is associated with depression. Hamilton, G., Evans, K. L., MacIntyre, D. J., Deary, I. J., Dominiczak, A. F., Smith, B. H., … Thomson, P. A. (2012). Neuroscience Letters, 510(1), 6-9.

Variants in the Complement receptor 1 (CR1) gene have been reported associated with Alzheimer's Disease. This study reports that women with recurrent depression are also more likely to carry these same CR1 variants.

 

Effect of Five Genetic Variants Associated with Lung Function on the Risk of Chronic Obstructive Lung Disease, and Their Joint Effects on Lung Function. Soler Artigas, M., Wain, L. V., Repapi, E., Obeidat, M., Sayers, I., Burton, P. R., … the SpiroMeta Consortium. (2011). American Journal of Respiratory and Critical Care Medicine, 184(7), 786–795.

The two papers by Soler Artigas in 2011 are the first major examples of how Generation Scotland has served to provide strong supporting evidence for the effect of specific genetic variants on lung function and, by implication, as risk factors for chronic obstructive pulmonary disease (COPD).

 

Genome-wide association and large scale follow-up identifies 16 new loci influencing lung function. Soler Artigas, M., Loth, D. W., Wain, L. V., Gharib, S. A., Obeidat, M., Tang, W., … Tobin, M. D. (2011). Nature Genetics, 43(11), 1082–1090.

The two papers by Soler Artigas in 2011 are the first major examples of how Generation Scotland has served to provide strong supporting evidence for the effect of specific genetic variants on lung function and, by implication, as risk factors for chronic obstructive pulmonary disease (COPD).

 

Is rigorous retrospective harmonization possible? Application of the DataSHaPER approach across 53 large studies. Fortier, I., Doiron, D., Little, J., Ferretti, V., L’Heureux, F., Stolk, R. P., … Burton, P. R. (2011). International Journal of Epidemiology, 40(5), 1314–1328.

The Generation Scotland team contributed to this EU FP7 project to build tools that allow data integration across cohort studies, particularly of value for replication studies and cross-cohort studies.

 

Sero-Prevalence and Incidence of A/H1N1 2009 Influenza Infection in Scotland in Winter 2009–2010. McLeish, N. J., Simmonds, P., Robertson, C., Handel, I., McGilchrist, M., Singh, B. K., … Woolhouse, M. E. J. (2011). PLoS ONE, 6(6), e20358.

In 2009, a new strain of flu, H1N1, swept the country and was associated with severe illness in a sub-set of otherwise healthy individuals. This begged the question as to just how many individuals in the population had been exposed to infection in order to model how many might become severely affected. Generation Scotland data was used to get a firm estimate of this, valuable for health planning. It turned out that about half of the popultion was exposed to infection, but fortunately only a small minority developed full blown and severe symptoms.

 

Generation Scotland: Donor DNA Databank; A control DNA resource. Kerr, S. M., Liewald, D. C., Campbell, A., Taylor, K., Wild, S. H., Newby, D., … Porteous, D. J. (2010). BMC Medical Genetics, 11, 166

This the key reference to one of the component parts of Generation Scotland, a biobank of 5,000 fully anonymised blood donor samples of great value as readily available controls for many different types of study.

 

Quality, quantity and harmony: the DataSHaPER approach to integrating data across bioclinical studies. Fortier, I., Burton, P. R., Robson, P. J., Ferretti, V., Little, J., L’Heureux, F., … Hudson, T. J. (2010). International Journal of Epidemiology, 39(5), 1383–1393.

The Generation Scotland team contributed to this EU FP7 project to build tools that allow data integration across cohort studies, particularly of value for replication studies and cross-cohort studies.

 

Shared Genetic Aetiology between Cognitive Ability and Cardiovascular Disease Risk Factors: Generation Scotland's Scottish Family Health Study. Luciano, M., Batty, G. D., McGilchrist, M. M., Linksted, P., Fitzpatrick, B., Jackson, C., … Deary, I. J. (2010). Intelligence, 38(3), 304-313.

This is an important early study from Generation Scotland. It demonstrates the enormous value of having tests of general cognitive ability alongside measures of physical health. In keeping with many other studies, this study shows that well-known risk factors account for about a third of the observed risk of heart disease. The rest is usually put down to environmental factors. What this study shows is that general cognitive ability accounts for another third or so of the risk, leaving just one third down to the environment.

 

Can the governance of a population genetic data bank effect recruitment? Evidence from the public consultation of Generation Scotland. Haddow, G., Cunningham-Burley, S., Murray, L. (2011). Public Understanding of Science, 20(1), 117-129.

Before starting recruitment to Generation Scotland, we discussed the ethical, legal and social issues relating to the research plan in great detail and held public engagement meetings to further understand and respond to issues arising in the final protocol, as described here.

 

Genome-wide association study identifies five loci associated with lung function. Repapi, E., Sayers, I., Wain, L. V., Burton, P. R., Johnson, T., Obeidat, M., … Tobin, M. D. (2010). Nature Genetics, 42(1), 36–44.

This paper describes the identification of five genetic factors that are associated with lung function and are candidates for risk of chronic obstructive lung disease. The measure we have for lung function in GS was FEV1, the amount of air that can be expelled in 1 second, a good overall measure of lung function. This was one of the genetic earliest studies of GS and demonstrated the value of the cohort for replicating findings made in other cohorts.  

 

"We only did it because he asked us": gendered accounts of participation in a population genetic data collection.  Haddow, G. (2009). Social Science & Medicine, 69(7), 1010-1017.

Before starting recruitment to Generation Scotland, we discussed the ethical, legal and social issues relating to the research plan in great detail, held public engagement meetings to further understand and respond to issues arising in the final protocol and interviewed a sample set of participants for further feedback, as described here.

 

Some principles and practices of genetic biobanking studies. MacLeod, A. K., Liewald, D. C., McGilchrist, M. M., Morris, A. D., Kerr, S. M., Porteous, D. J., (2009). European Respiratory Journal, 33(2), 419-425.

This paper reviews some of the guiding principles behind the Generation Scotland study that are useful for others thinking about setting up similar studies elsewhere.

 

Data integration in eHealth: a domain/disease specific roadmap. Ure, J., Procter, R., Martone, M, Porteous, D. J., Lloyd, S., Lawrie, S., … Wardlaw, J. (2007). Studies in Health Technology and Informatics, 126, 144-153.

This paper uses Generation Scotland as an example of how to use the capacity to link health records electronically.

 

Tackling community concerns about commercialisation and genetic research: a modest interdisciplinary proposal. Haddow, G., Laurie, G., Cunningham-Burley, S., Hunter, K. G. (2007). Social Science & Medicine, 64(2), 272-282.

Before starting recruitment to Generation Scotland, we discussed the ethical, legal and social issues relating to the research plan in great detail and held public engagement meetings to further understand and respond to issues arising in the final protocol. Here we discuss issues relating to commencialisation.

 

Generation Scotland: the Scottish Family Health Study; a new resource for researching genes and heritability. Smith, B. H., Campbell, H., Blackwood, D., Connell, J., Connor, M., Deary, I. J., … Morris, A. D. (2006). BMC Medical Genetics, 7, 74.

This paper provides the first comprehensive description of the Generation Scotland resource. It is one of two primary references to be used when citing the resource, the second being Smith et al., 2013, IntJEpidemiol.

 

Genetic epidemiology and primary care. Smith, B. H., Watt, G. C., Campbell, H., & Sheikh, A. (2006). The British Journal of General Practice, 56(524), 214–221.

This paper discusses and develops some of the ideas behind Generation Scotland in relation to primary care research and genetic epidemiology.