Principal Investigator: Professor Andrew Morris
Department: Department of Biostatistics
Institution: University of LiverpoolTags: 15390, Association, Confounding, population genetics, Population Structure
1a: The United Kingdom (UK) is a genetically diverse nation with strong genetic
differences between regions, which may adversely affect genome-wide
association studies of complex human traits if not accounted for in the analysis.
The aim of the proposed project is to evaluate the impact of population
structure on genetic association studies of complex traits with common and rare
variants, and to compare approaches to account for ancestral confounding.
1b: Our study will inform the application of methodology and interpretation of
results of genome-wide association studies of complex human traits using UK
Biobank data, thereby minimising the potential for false positive findings and
increasing power to detect true association signals. In this way, our study will be
relevant to genetic studies of all clinical outcomes considered in UK Biobank,
with the potential to lead to the prevention, diagnosis and treatment of disease.
1c: We will consider a range of methodologies to detect population structure
(based on participant postcode data), and assess their suitability for correction
for ancestral confounding. We will identify genetic variants that are confounded
with ancestry, and assess their impact on association analyses with physical
measures (blood pressure, anthropometry and spirometry) taken at the
assessment centre, and self-reported type 2 diabetes, myocardial infraction and
asthma from the verbal interview. We will also use the genotype data to
simulate traits under alternative models of structure, and assess the impact on
association findings for both common and rare variants.
1d: This analysis will include the full cohort.