Demonstrating stratification in a European American population

Area of Science:

• Genetics
• Population Genetics
• Human Genetics

Background:

• Population stratification, where allele frequencies differ due to ancestry, can lead to spurious associations in case-control genetic studies.
• While often debated, significant stratification in European-derived populations remains a possibility, potentially impacting heritable trait research.
• Previous empirical studies showed limited evidence of stratification in European populations, but did not entirely rule out its potential impact.

Purpose of the Study:

• To investigate population stratification in a European American cohort using height as a heritable trait.
• To assess the effectiveness of standard analytical methods in detecting stratification.
• To identify if a specific genetic variant, LCT, contributes to stratification-related height associations.

Main Methods:

• Genotyping of 178 single nucleotide polymorphisms (SNPs) in a European American panel.
• Application of standard analytical methods for association studies.
• Stratification analysis by rematching individuals based on European ancestry and analyzing subgroups (Polish, Scandinavian).

Main Results:

• Standard methods did not reveal population stratification.
• A single nucleotide polymorphism (SNP) in the LCT gene showed a strong association with height (P < 10^-6).
• This association was largely attributed to stratification, diminishing significantly after ancestry-informed rematching and disappearing in subgroup analyses.

Conclusions:

• A specific LCT gene SNP's association with height was an artifact of population stratification.
• Standard methods may fail to detect stratification, particularly when allele frequencies vary significantly across subpopulations.
• Novel methods are likely necessary for robustly identifying and correcting for population stratification in genetic association studies.