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

Data from over 4,000 sibling groups, totalling 11,000 of our volunteers, were studied in this international research involving 18 other research studies.

Genetic studies aim to find regions of the genome that may be linked to certain health conditions and other traits. A new study has shown that, for social traits, these genetic effects are due to a mixture of direct effects (e.g. biological effects of DNA), and indirect effects (e.g. family or social environment). Whereas biological traits are mainly driven by direct effects.

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

The researchers found that the genetics of many social traits – like educational attainment, age of first child and depression – are strongly influenced by family or social environments. In contrast, the genetic influences on more biological traits – such as cholesterol and BMI – were found to be less likely to be influenced by family or social environments.

The research was led by the University of Bristol’s Population Health Sciences (PHS), MRC Integrated Epidemiology Unit (IEU) and K.G. Jebsen Center for Genetic Epidemiology at Norwegian University, studied genetic, education attainment and health data on siblings from 19 studies across four continents.

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

This type of study usually estimates the links between millions of common genetic variants across the genome using samples of unrelated individuals. However, this study used siblings to estimate genetic effects. It is a technique that exploits the random process of meiosis to protect against confounding. Whether a pair of siblings shares a particular genotype is entirely random, so if the siblings who share the genotype have more similar trait measures, researchers can be more confident that the genotype is influencing the trait directly.

The team demonstrated that previously reported genome-wide association study (GWAS) associations, which typically use more widely available population samples, tend to overestimate direct effects for many traits including educational attainment, cognitive ability, age when first gave birth, whether someone has ever smoked, depressive symptoms and number of children. Furthermore, they found that estimates of heritability, genetic correlations and other genetic analysis methods could substantially differ when calculated using estimates from siblings. However, in some cases, there is a more complicated picture. For example, height is highly heritable, but the study found evidence that some of these differences may be attributed to the selection processes that parents made in choosing their partners.

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 mother, father, offspring trios.

Paper Their findings are published today [9 May] in Nature Genetics.

Within-sibship GWAS improve estimates of direct genetic effects by Howe et al in Nature Genetics