An atlas of disease-specific lifetime reproductive success




Principal Investigator:

Andrea Ganna


Karolinska Institutet

Start Date:


End Date:


Primary Classification:

30302: Public Health, Global Health, Social Medicine and Epidemiology


  • Castor /proj at UPPMAX: 800 GiB
  • Cygnus /proj at UPPMAX: 800 GiB
  • Castor /proj/nobackup at UPPMAX: 200 GiB
  • Cygnus /proj/nobackup at UPPMAX: 200 GiB
  • Bianca at UPPMAX: 10 x 1000 core-h/month


Lifetime reproductive success, defined as the total number of offspring an individual produces over its entire reproductive lifespan, is a widely used measure of fitness. Individuals that develop certain diseases, typically early onset, are characterized by a reduced reproductive success. Power et al. [PMID: 23147713] have been exploring the fecundity of individuals with psychiatric disorders and showed that these individuals are characterized by reduced fertility. Moreover, they could use a family design to understand if unaffected siblings of those with psychiatric disorders would enjoy increased reproductive fitness, which would be consistent with a balancing selection hypothesis. However, there is not a comprehensive assessment of lifetime reproductive success across many different diseases. Why it is important to study this? There are two main reasons. First, quantifying the lifetime reproductive success can help to understand the genetic architecture of diseases and to inform the design of genetic studies. The relative contribution of rare coding mutations to the genetic architecture of diseases relates to the selection acting against the disease. Therefore, certain study design, e.g. family-based exome sequencing studies, might be more appropriate for disorders characterized by a low lifetime reproductive success. Second, an accurate estimate of lifetime reproductive success can provide public-health information that is relevant for patients and for doctors. We propose to explore the lifetime reproductive success across multiple diseases using Scandinavian health registries. These registries have been collecting health information from the 70’s and comprise a generation of individuals which have been covered by registries for the majority of their reproductive lifespan. By combining health registries with registries containing family relationships we can quantify, for each disease, the lifetime reproductive success by comparing the number of children in diseased individuals with those in the general population. We will need to account for cohort effect and possible confounding by social-economic status. For a subset of these individuals, we can also explore the impact of the disease on the number of grandchildren, which is a better proxy of fitness. Finally, a particular focus would be directed to understand how different neurodevelopmental and psychiatric-related co-morbidities patterns might impact lifetimes reproductive success.