Measuring and using admixture to study the genetics of complex diseases

Area of Science:

• Evolutionary genetics
• Genomic medicine
• Population genetics

Background:

• Admixture is a significant evolutionary process impacting complex disease genetics.
• Admixture linkage disequilibrium (ALD) arises from admixture and persists over long genetic distances in recently admixed populations.

Purpose of the Study:

• To explore the utility of admixture and ALD in complex disease genetics.
• To review admixture mapping (AM) methodologies, including marker selection and population stratification.
• To discuss the implications of AM for gene mapping studies using a model phenotype.

Main Methods:

• Discussion of various admixture models and their influence on AM study success.
• Review of methods for detecting and controlling population stratification in genetic studies.
• Analysis of ancestry-phenotype correlations in case/control and AM studies.

Main Results:

• ALD extent is influenced by admixture level, marker informativeness, and population admixture dynamics.
• Population stratification, arising from variations in individual admixture, can be a source of power or a confounder in genetic association studies.
• Individual ancestry-phenotype correlations have been demonstrated, with skin pigmentation serving as a model.

Conclusions:

• Admixture and ALD are valuable tools for complex disease genetics, but require careful methodological consideration.
• Effective marker selection and robust control for population stratification are essential for successful admixture mapping.
• Understanding the limitations of AM is critical for designing effective studies in complex disease gene mapping.