International siblings study sheds new light on the nature of the genetics of disease

Data from groups of siblings – brothers and sisters – including 1,800 of our ORCADES and Viking Health Study - Shetland volunteers, were studied in this international research.

Two Sibling Barbara and James and their sibling dogs

An international group of 100 researchers studied 178,076 siblings to estimate the effects of their genetics and environment on their health and social lives.

They found that the genetics of many social traits – like educational attainment, age when first gave birth, smoking and depression – are strongly influenced by family environments or social effects, like more common marriages between similar individuals. In contrast, the genetics of biological traits – such as bad cholesterol and body mass index (how much you weigh compared to your height) – were found to be less likely to be influenced by these effects.

The researchers studied genetic, education and health data on siblings from 19 studies across four continents. The research included data from 1,811 of our volunteers, who took part in ORCADES and the Viking Health Study – Shetland and had a brother or sister in the study.

They used a research method known as a Genome-Wide Association Study (GWAS) on data from the siblings. It was used to help find any genetic links between health conditions and millions of common genetic variants.

Genome-Wide Association Studies usually use samples of unrelated individuals. However, this new study used siblings to estimate genetic effects. The pieces of DNA passed on to siblings from their parents are entirely random. This means that if the siblings who share them have more similar trait measures, researchers can be more confident that this set of genes is influencing the trait directly - because siblings share the same family and social environment. This is not the case for studies of unrelated people, where those who have more children or are more likely to smoke may also share factors other than genetics.

In fact, the team showed that previously reported GWAS associations - which did not focus on siblings - tend to overestimate the effect of DNA on many traits including:

  • Length of time in education
  • Cognitive ability
  • Age when first gave birth
  • Whether someone has ever smoked
  • Depressive symptoms
  • Number of children

Furthermore, they found that estimates of a number of important genetic measures -  such as how much of a trait is due to genes (heritability) and how much of the genetics is shared between traits (genetic correlation) - were distorted when not calculated using estimates from siblings.

Our findings suggest large-scale family datasets provide new opportunities to quantify direct effects of genetic variation on human traits and diseases. Looking at sociological questions and genetics together is a powerful tool for understanding why different health and social outcomes happen, providing better insight for potential interventions and treatments.

Dr Laurence Howe
Lead Author

The international collaboration established for this study is continuing to work together and explore these issues further, including looking at associations between trios consisting of mother, father, and offspring.

Their findings are published in Nature Genetics:

Within-sibship genome-wide association analyses decrease bias in estimates of direct genetic effects