The Lifecourse GWAS Consortium

The Lifecourse GWAS Consortium is an international collaboration led by researchers at the MRC Integrative Epidemiology Unit, University of Bristol. It brings together 50 cohort studies and biobanks to investigate how genetic associations with complex traits vary across the lifecourse.

Genome-wide association studies commonly combine measurements collected at different ages and therefore implicitly assume that genetic associations remain constant over time. However, genetic variants may influence traits differently at different stages of life. The Lifecourse GWAS Consortium addresses this by generating harmonised, age-, sex- and ancestry-stratified genome-wide association results for 26 phenotypes measured from infancy to later adulthood.

Aim

The Consortium aims to investigate whether genetic associations vary systematically across the lifecourse and to improve understanding of the temporal genetic architecture of complex traits.

Objectives

The Consortium’s objectives are to:

  1. Generate harmonised genome-wide association results for 26 anthropometric, cardiometabolic, inflammatory, respiratory, endocrine and other health-related phenotypes.
  2. Conduct analyses at annual ages from infancy to 19 years, in five-year age groups across adulthood, and within broader life stages.
  3. Examine genetic associations separately by sex and across European, African, East Asian, South Asian and admixed or other ancestry groups.
  4. Combine results across contributing studies using methods that account for overlap between participants contributing measurements at different ages.
  5. Identify genetic variants whose associations vary with age and model the timing and pattern of these changes across the lifecourse.
  6. Group variants according to shared patterns of age-varying genetic association.
  7. Investigate the biological and methodological drivers of age-varying genetic associations, including biological pathways, pleiotropy, selection bias and scale effects.
  8. Evaluate how the predictive performance of polygenic risk scores varies across age, sex and ancestry.
  9. Generate genetic instruments for downstream lifecourse Mendelian randomisation analyses examining whether the effects of selected exposures differ between life stages.

Participating studies and biobanks

The Consortium includes studies spanning childhood, adolescence and adulthood from Europe, North America, Asia and Australia. Together, they provide measurements across a wide range of ages and ancestral groups.

Working group

The working group is responsible for the Consortium’s scientific direction, coordination and delivery:

  • Grace M. Power (lead) — University of Bristol and The University of Queensland
  • Genevieve Leyden — University of Bristol
  • David Carslake — University of Bristol
  • Roya Karimi — University of Bristol and University of Bergen
  • Stefan Johansson — University of Bergen
  • George Davey Smith — University of Bristol
  • Eleanor Sanderson (supervision) — University of Bristol
  • Gibran Hemani (supervision) — University of Bristol

Steering committee

The steering committee provides strategic and scientific guidance:

  • Maria Carolina Borges — University of Bristol
  • Neil Davies — University College London and Norwegian University of Science and Technology
  • Rachel M. Freathy — University of Exeter
  • Diana Kuh — University College London
  • Nicole Warrington — The University of Queensland

Code review

Review of the Consortium’s analysis code is undertaken by:

  • Aimee Hanson — University of Bristol
  • Venexia Walker — University of Bristol and University of Pennsylvania

Contact

For enquiries about the Consortium, collaboration or use of its emerging resources, please contact lifecourse-gwas-group@bristol.ac.uk.