Insights into the genetics of human height
Generation Scotland and VIKING genes data used to help identify genetic variants associated with height
Data from Generation Scotland, ORCADES and Viking Health Study – Shetland has formed part of the largest ever genetic study, helping to identify 12,000 genetic variants associated with height. The study, recently published in Nature (link below) comes from a large number of authors, including the GIANT consortium (Genetic Investigation of Anthropometric Traits). Generation Scotland has been part of the GIANT consortium since 2014, and has contributed genetic data from 20,000 consented volunteers to several of their studies.
During the largest genome-wide association study (GWAS) reported to date, researchers performed genetic analyses of an incredible 5.4 million research volunteers across hundreds of cohorts (including those from Generation Scotland and VIKING genes). They identified 12,111 independent genetic variants that are significantly associated with height.
Adult height is heritable and easily measurable. Previous research identified a large number of genetic variants associated with height, including genes associated with skeletal disorders.
Height provides a model trait for assessing the role of genetic variation in the architecture of observable human traits. Many observable or measurable traits are inherited, such as height, eye colour and blood type, but also blood pressure, cholesterol levels, blood sugar, cognitive abilities and other risk factors for disease. In each case, the measured trait is determined by both their genomic makeup and environmental factors. Height is studied as a model for other traits as it is very widely measured and so what geneticists can learn about height paves the way for what they might be able to learn about disease-related traits, as sample sizes increase.
Lead author, Loïc Yengo and colleagues from the GIANT consortium, suggest these variations account for nearly all common variants associated with height, particularly in populations of European ancestry (75.8% of the sample had predominantly European ancestry). When they looked at the position of these variants across the genome, they found variants were more likely to be clustered close to genes already known to be associated with growth disorders. The authors indicate that the genetic variants associated with height identified in this study account for 40% of the variation in height in populations with European ancestry, but only around 10–20% in other ancestries.
The findings demonstrate that, with sufficiently large sample sizes, researchers can produce a saturated map of regions in the genome that contribute to variation: the vast majority of common height-associated genetic variants have been found. They conclude that further research is needed in groups of non-European ancestries to achieve the same level of saturation as seen in Europeans.
Generation Scotland is proud to have played a small part in this huge study, which has found the “missing heritability” of genetic variations in height, and also demonstrated the limit (saturation point) of what can be discovered by meta-analysis of millions of samples.