Generation Scotland

Genetics, Genealogy and Health

Case studies in the field of genetics, genealogy and health.

By recruiting participants from around Scotland in family groups and studying their DNA, we can address many interesting genealogical and health related questions. Examples include the demonstration that the rate at which new mutations arise in the offspring of parents is, as predicted, influenced by the age of the biological parent, but more surprisingly perhaps, varies quite significantly between families, irrespective of parental age. This realisation could have important implications for genetic counselling in families.

GS study ID: GS10051 Hurles

Key reference: Timing, rates and spectra of human germline mutation. Rahbari, R., Wuster, A., Lindsay, S. J., Hardwick, R. J., Alexandrov, L. B., Al Turki, S., … Hurles, M. E. (2015). Nature Genetics, 48(2), 126-133.


In other work, we have shown mutations in genes that would be expected to have a detrimental effect are sometimes seen in individuals with no hallmark of illness. This suggests that first, we need to be cautious about interpreting the potential consequences of a gene test, but also that there may be compensatory mechanisms for a gene defect that could point to a new approach to treatment.

GS study ID: GS12121 Wilson

Key reference: Homozygous loss-of-function variants in European cosmopolitan and isolate populations. Kaiser, V. B., Svinti, V., Prendergast, J. G., Chau, Y.-Y., Campbell, A., Patarcic, I., … Wilson, J. F. (2015). Human Molecular Genetics, 24(19), 5464–5474.


By also having detailed information on where people live, their occupations and lifestyle, we can also get a better idea of the respective influence of nature (genes) and nurture (environment). Because of the family based structure of GS, we can estimate the effect of the shared (same household, unrelated partner) and non-shared (external, personal) environment. This could have important implications for how health services should plan and deliver medical interventions for conditions like obesity.

GS study ID: GS14190 McIntosh

Key reference: Shared genetics and couple-associated environment are major contributors to the risk of both clinical and self-declared depression.  Zeng, Y., Navarro, P., Xia, C., Amador, C., Fernandez-Pujals, A. M., Thomson, P. A., … McIntosh, A. M. (2016). EBioMedicine, 14: 161-167.


Evolution and ‘survival of the fittest’ tends to weed out harmful genes, whereas inbreeding is linked to reduced fitness. GS contributed to a study of over 350,000 individuals to show that the children of parents who are more distantly related tend to be taller and smarter than their peers, arguing that increased height, better lung function and higher intelligence have all been positively selected for in human history.

GS study ID: GS12121 Wilson

Key reference: Directional dominance on stature and cognition in diverse human populations (ROHgen). Joshi, P. K., Esko, T., Mattsson, H., Eklund, N., Gandin, I., Nutile, T., … Wilson, J. F. (2015). Nature,523(7561), 459-462.


In a similar vein, by combining GS data with other large studies (over 130,000 participants in total), genes which influence educational attainment (years at school and continuing education) were shown to have a small, but measurable, effect on increasing life expectancy.

GS study ID: GS13152 Deary

Key reference: Genetic variants linked to education predict longevity. Marioni, R. E., Ritchie, S. J., Joshi, P. K., Hagenaars, S. P., Okbay, A., Fischer, K., … Deary, I. J. (2016). PNAS. 113 (47) 13366-13371.