Generation Scotland


Research publications from 2014.

Large-scale discovery of novel genetic causes of developmental disorders. Fitzgerald, T.W., Gerety, S. S., Jones, W. D., van Kogelenberg, M., King, D. A., McRae, J., … Hurles, M. E. (2014). Nature, 519(7542), 223-228.

The Deciphering Developmental Disorders (DDD) Consortium was set up to identify the basis of paediatric cases of developmental delay with a suspected genetic origin. Generation Scotland was able to help the DDD study by providing  valuable reference data to avoid misinterpretation of rare genetic variants identified by whole exome sequencing of unsolved cases.


Stratification by Smoking Status Reveals an Association of CHRNA5-A3-B4 Genotype with Body Mass Index in Never Smokers. Taylor, A. E., Morris, R. W., Fluharty, M. E., Bjorngaard, J. H., Åsvold, B. O., Gabrielsen, M. E., … Sattar, N. (2014). PLoS Genetics, 10(12), e1004799.

In another collaboration with the Causal Analysis Research in Tobacco and Alcohol (CARTA) consortium, Generation Scotland data helped reveal an unexpected finding that a genetic variant in the gene CHRNA5-A3-B4 which is associated with heavy smoking and lower body mass index is unexpectedly also associated with higher BMI in never smokers. This study emphasises the value and importance of cohorts such as GS that have very detailed and varied measures on all participants


Investigating the possible causal association of smoking with depression and anxiety using Mendelian randomisation meta-analysis: the CARTA consortium. Taylor, A. E., Fluharty, M. E., Bjørngaard, J. H., Gabrielsen, M. E., Skorpen, F., Marioni, R. E., … Munafò, M. R. (2014). BMJ Open, 4(10), e006141.

In another collaboration with the Causal Analysis Research in Tobacco and Alcohol (CARTA) consortium, Generation Scotland data was used to test and refute a suggested causal association between smoking and depression.


Common genetic variants associated with cognitive performance identified using the proxy-phenotype method. Rietveld, C. A., Esko, T., Davies, G., Pers, T. H., Turley, P., Benyamin, B., … Koellinger, P. D. (2014). Proceedings of the National Academy of Sciences of the United States of America, 111(38), 13790–13794.

Using educational attainment as a proxy for cognitive performance, this large, collaborative study combining Generation Scotland data with other cohorts (over 100,000 subjects in total) found good evidence that four genes in particular (KNCMA1, NRXN1, POU2F3 and SCRT) contribute to individual differences in cognitive performance. Of note, these four genes are all involved in synaptic plasticity, the main cellular mechanism in learning and memory. 


Novel Approach Identifies SNPs in SLC2A10 and KCNK9 with Evidence for Parent-of-Origin Effect on Body Mass Index. Hoggart, C. J., Venturini, G., Mangino, M., Gomez, F., Ascari, G., Zhao, J. H., … Kutalik, Z. (2014). PLoS Genetics, 10(7), e1004508.

Generation Scotland was one of several cohorts that combined data to show that body mass index was more influenced if the risk variants in the genes SLC2A10 and KCNK9 were inherited from the father than the mother.


Targeted genetic testing for familial hypercholesterolaemia using next generation sequencing: a population-based study. Norsworthy, P. J., Vandrovcova, J., Thomas, E. R., Campbell, A., Kerr, S. M., Biggs, J., … Aitman, T. J. (2014). BMC Medical Genetics, 15, 70.

Familial hypercholesterolaemia is a genetic form of heart disease that is effectively treated by cholesterol lowering drugs, such as statins, but dangerous if untreated. This study in the Generation Scotland cohort demonstrated the feasiblity of using next generation DNA sequencing to provide definitive testing for this inherited disorder.


Genome-wide association analysis identifies six new loci associated with forced vital capacity. Loth, D. W., Artigas, M. S., Gharib, S. A., Wain, L. V., Franceschini, N., Koch, B., … London, S. J. (2014). Nature Genetics, 46(7), 669–677.

We measured depth and strength of breathing in all Generation Scotland participants. This study builds on the earlier Soler Artigas studies and identifies 6 new genes that influence lung function and may affect risk of COPD.


Molecular genetic contributions to socioeconomic status and intelligence. Marioni, R. E., Davies, G., Hayward, C., Liewald, D., Kerr, S. M., Campbell, A., … Deary, I. J. (2014). Intelligence, 44(100), 26–32.

This study shows that there is a strong correlation between socioeconomic status (SES), education and cognition (thinking skills and memory). The correlation between SES and education is usually put down to the environment, but we know that cognition is highly heritable. This study confirms a sizeable genetic component to the correlation between these traits (18-29%).


Identification of susceptibility loci for colorectal cancer in a genome-wide meta-analysis. Whiffin, N., Hosking, F. J., Farrington, S. M., Palles, C., Dobbins, S. E., Zgaga, L., … Dunlop, M. G. (2014). Human Molecular Genetics, 23(17), 4729–4737.

Generation Scotland provided vital control data for this large study looking for novel genetic risk factors for colon cancer. A new risk locus on chromosome 10 was reported. The study challenged earlier published findings in two genes, but also new and different evidence that these genes might be involved.


Does a history of depression actually mediate smoking-related pain? Findings from a cross-sectional general population-based study. van Hecke, O., Torrance, N., Cochrane, L., Cavanagh, J., Donnan, P. T., Padmanabhan, S., … Smith, B. H. (2014). European Journal of Pain, 18(9), 1223-1230.

Generation Scotland participants told us about their smoking habits, the pain they experienced and whether they had suffered from depression. This study examined the relationship between smoking, pain and depression. We found that in those who had a history of depression this did influence the link between smoking and pain, but not in those without a history of depression.


Common Genetic Variants Explain the Majority of the Correlation Between Height and Intelligence: The Generation Scotland Study. Marioni, R. E., Batty, G. D., Hayward, C., Kerr, S. M., Campbell, A., Hocking, L. J., … Deary. (2014). Behavior Genetics, 44(2), 91–96.

Height and general cognitive ability are both highly heritable. Both traits are easily measured. Genetic studies have pointed towards many genes, each of very small effect combining to explain individual differences in each trait. Height and general intelligence are correlated, and crudely put and averaged out, that means ' taller, smarter'.  This study used a well-founded statistic test to show that common genetic variants explain essentially all of that correlation.