Projects
The Consortium’s principal analysis examines how genetic associations with 26 phenotypes vary from infancy to later adulthood.
Analysis design
Participating studies use harmonised phenotype definitions and a centrally developed pipeline to conduct genome-wide association analyses stratified by:
- Age or life stage
- Sex
- Ancestry
Analyses are conducted at annual ages from infancy to 19 years and in five-year age groups from age 20 onwards. Analyses are also conducted within broader life stages spanning birth, infancy and toddlerhood, early childhood, middle childhood, adolescence, young adulthood, middle adulthood and later adulthood.
Each phenotype and age or life-stage combination is analysed as a separate cross-sectional genome-wide association study. Participants with measurements at multiple ages can contribute to more than one age-specific analysis, but individual longitudinal trajectories are not modelled directly.
Study-specific results are quality controlled and combined through fixed-effects meta-analysis. Meta-analyses are conducted within European, African, East Asian, South Asian and admixed or other ancestry groups, as well as across all available ancestry groups.
Phenotypes
The following 26 phenotypes are included:
| Phenotype group | Phenotypes |
|---|---|
| Body size and composition | Body mass index; BMI-for-age z-score; height; waist circumference; waist-to-hip ratio; total body bone mineral density |
| Respiratory function | Forced expiratory volume in one second (FEV1); FEV1/FVC ratio |
| Blood pressure | Systolic blood pressure; diastolic blood pressure; pulse pressure |
| Lipids | LDL cholesterol; HDL cholesterol; triglycerides |
| Metabolic and inflammatory traits | C-reactive protein; interleukin 6; leptin; glycated haemoglobin (HbA1c); insulin; adiponectin |
| Nutritional and mineral traits | Calcium; vitamin D |
| Reproductive hormones | Oestradiol; total testosterone; bioavailable testosterone; sex hormone-binding globulin |
Detailed definitions and preprocessing instructions are available in the phenotype definitions section of the analysis wiki.
Phase 1: Age-, sex- and ancestry-stratified GWAS
Participating studies apply the central analysis pipeline to generate genome-wide association results for each available phenotype, age or life-stage, sex and ancestry stratum.
The pipeline standardises:
- Phenotype preparation
- Age and life-stage classification
- Ancestry classification
- Genetic quality control
- Polygenic risk score analyses
- Genome-wide association analyses
Instructions and code for cohort analysts are available through the Lifecourse GWAS analysis wiki.
Phase 2: Age-varying genetic associations
Genome-wide significant variants are evaluated across age groups and life stages. Meta-regression is used to test whether their associations vary with age while accounting for overlap between participants contributing to different age-specific analyses.
Association patterns are then smoothed and clustered to identify groups of variants with similar age-varying profiles. These may include associations that increase, decrease, emerge or peak at particular stages of life.
Sensitivity analyses examine whether observed patterns could be influenced by methodological factors, including selection bias and scale effects.
Phase 3: Biological interpretation and downstream analyses
Subsequent analyses will:
- Compare age-varying genetic associations across sex and ancestry groups
- Investigate functional enrichment and biological pathways
- Examine pleiotropy among variants with age-varying associations
- Evaluate the performance of polygenic risk scores across ages
- Develop and evaluate life-stage-specific polygenic risk scores
- Apply lifecourse Mendelian randomisation to selected exposure–outcome relationships
Current status
The harmonised cohort-level analysis pipeline has been implemented across participating studies. Age-, sex- and ancestry-stratified results are currently being quality controlled and combined through meta-analysis.
Extension projects
The Consortium welcomes proposals for additional projects that build on its infrastructure, data and methods.
New or existing Consortium members wishing to propose an extension project should complete the project proposal form and submit it to the working group.
Proposals will be reviewed by the working group and steering committee for scientific relevance, feasibility and overlap with existing work. The lead of an approved project will be responsible for establishing an appropriate working group, delivering the research and ensuring that the contribution of the Lifecourse GWAS Consortium is appropriately recognised.
Further information about project leadership, authorship, software and data sharing is provided in the Consortium’s Principles of Collaboration.
Data requests
Researchers from participating studies who wish to request access to emerging Consortium summary data should complete the early data request form.
Requests will be reviewed in accordance with the Consortium’s Principles of Collaboration and any restrictions imposed by contributing studies.
For questions about projects or data requests, please contact lifecourse-gwas-group@bristol.ac.uk.