Dutch population structure across space, time and GWAS design

Area of Science:

• Population Genetics
• Human Ancestry
• Genomic Epidemiology

Background:

• Previous genetic studies in the Netherlands lacked resolution due to limited markers and external data.
• Understanding fine-grained population structure is crucial for accurate genetic analyses.

Purpose of the Study:

• To investigate fine-scale population genetic structure and demographic history across the Netherlands.
• To apply advanced haplotype sharing methods to genome-wide data for enhanced resolution.
• To assess the impact of fine-scale genetic structure on Genome-Wide Association Studies (GWAS).

Main Methods:

• Utilized genome-wide single nucleotide polymorphism (SNP) data from 1,626 individuals.
• Applied advanced haplotype sharing methods, including ChromoPainter and fineSTRUCTURE.
• Integrated geographical data for 1,422 individuals to link genetic clusters with location.

Main Results:

• Identified 40 distinct haplotypic clusters with significant north-south variation and intra-provincial differentiation.
• Observed genetic clustering influenced by ancestry gradients from neighboring regions and gene flow across Dutch rivers.
• Demographic estimates indicated population crashes coinciding with the Black Death, despite overall population growth.
• Demonstrated that GWAS incorporating fine-grained haplotypic covariates are less confounded.

Conclusions:

• The Netherlands exhibits complex, fine-grained population genetic structure with stable north-south and transient west-east components.
• Historical migrations and geographical features like rivers have shaped Dutch genetic landscape.
• Incorporating detailed haplotypic information enhances the accuracy of genetic association studies.