Related Experiment Video
Updated: Jun 18, 2026
13:55
Combined Immunofluorescence and DNA FISH on 3D-preserved Interphase Nuclei to Study Changes in 3D Nuclear Organization
Published on: February 3, 2013
Population stratification and patterns of linkage disequilibrium
Anthony L Hinrichs1, Emma K Larkin, Brian K Suarez
1Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri 63110, USA. tony@fire.wustl.edu
Genetic Epidemiology
|November 20, 2009
Summary
Population stratification in genetic studies inflates false positives. Statistical methods like genomic control and principal-components analysis can address ancestral differences in cases and controls for accurate association testing.
Area of Science:
- Population genetics
- Statistical genomics
- Bioinformatics
Background:
- Genome-wide association studies (GWAS) require careful selection of cases and controls from the same population to avoid false-positive findings.
- Population substructure, or differing ancestral backgrounds between cases and controls, can lead to inflated statistical significance due to allele frequency differences.
- High-throughput genotyping technologies enable the analysis of numerous markers necessary for addressing population stratification.
Framework:
- Statistical approaches like genomic control, structured association, and multivariate reduction analyses are employed to assess ancestral comparability.
- Principal-components analysis (PCA) or multidimensional scaling can identify and control for population structure by including principal components as covariates in regression models.
- Methods exist to handle population stratification even when genome-wide markers are unavailable, focusing on explicit stratification computation.
Implementation:
- Genetic Analysis Workshop 16 data revealed continuous axes of ethnic variation, demonstrating the prevalence of population substructure.
- Ignoring population structure resulted in P-value inflation across various phenotypes.
- Principal-components analysis effectively controlled inflation when used as covariates in logistic regression, allowing for local ancestry estimation and inclusion of related individuals.
Implications:
- Accurate control for population stratification is crucial for the validity of GWAS and genetic association studies.
- Failure to account for substructure can lead to erroneous conclusions and inflated false-positive rates.
- Developed methods offer robust solutions for association testing in diverse or admixed populations, enhancing the reliability of genetic discoveries.
Related Concept Videos
01:18Dihybrid Crosses
Overview
01:43Sex Linked Disorders
Like autosomes, sex chromosomes contain a variety of genes necessary for normal body function. When a mutation in one of these genes results in biological deficits, the disorder is considered sex-linked.
01:49Hardy-Weinberg Principle
Diploid organisms have two alleles of each gene, one from each parent, in their somatic cells. Therefore, each individual contributes two alleles to the gene pool of the population. The gene pool of a population is the sum of every allele of all genes within that population and has some degree of variation. Genetic variation is typically expressed as a relative frequency, which is the percentage of the total population that has a given allele, genotype or phenotype.In the early 20th century,...
02:03Law of Independent Assortment
While Mendel’s Law of Segregation states that the two alleles for one gene are separated into different gametes, a different question of how different genes are inherited remains. For example, is the gene for tall plants inherited with the gene for green peas? Mendel asked this question by experimenting with a dihybrid cross; a cross in which both parents are homozygous for two distinct traits resulting in an F1 generation that are heterozygous for both traits.
02:03Law of Independent Assortment
While Mendel’s Law of Segregation states that the two alleles for one gene are separated into different gametes, a different question of how different genes are inherited remains. For example, is the gene for tall plants inherited with the gene for green peas? Mendel asked this question by experimenting with a dihybrid cross; a cross in which both parents are homozygous for two distinct traits resulting in an F1 generation that are heterozygous for both traits.
01:49Law of Segregation
When crossing pea plants, Mendel noticed that one of the parental traits would sometimes disappear in the first generation of offspring, called the F1 generation, and could reappear in the next generation (F2). He concluded that one of the traits must be dominant over the other, thereby causing masking of one trait in the F1 generation. When he crossed the F1 plants, he found that 75% of the offspring in the F2 generation had the dominant phenotype, while 25% had the recessive phenotype.