Whole-genome sequencing in a well characterized high kinship cohort to identify the rare variant landscape of complex traits




Principal Investigator:

Åsa Johansson


Uppsala universitet

Start Date:


End Date:


Primary Classification:

30107: Medical Genetics


  • Cygnus /proj at UPPMAX: 150000 GiB
  • Castor /proj at UPPMAX: 150000 GiB
  • Cygnus /proj/nobackup at UPPMAX: 45000 GiB
  • Castor /proj/nobackup at UPPMAX: 45000 GiB
  • Bianca at UPPMAX: 200 x 1000 core-h/month


Genome-wide association studies (GWAS) have successfully identified many genes involved in development of complex diseases. However, GWAS have highlighted that only a small proportion of the genetic contribution to complex diseases can be explained by the genetic variants identified. Much of this “missing heritability” is due to the effect of many rare variants, which are often specific to individual populations or even families and not detected using standard GWAS with unrelated participants. Therefore, sequencing efforts to identify association between rare variants and diseases has predominantly been successful in monogenetic familiar diseases. A powerful resource for the identification of rare variants in complex diseases is kinship-structured populations, where the samples comprise families or individuals from a limited geographic area. One such population is the Northern Sweden population health study (NSPHS) that has shown a high level of kinship, and where thousands of clinical traits have been measured. We are now extending the data collection in the NSPHS with whole-genome sequencing of the whole cohort to investigate the effect of rare and population specific variants on human phenotypic traits.