scholarly journals Pathway-based analysis for genome-wide association studies using supervised principal components

2010 ◽  
Vol 34 (7) ◽  
pp. 716-724 ◽  
Author(s):  
Xi Chen ◽  
Lily Wang ◽  
Bo Hu ◽  
Mingsheng Guo ◽  
John Barnard ◽  
...  
Keyword(s):  
Principal Components ◽  
Association Studies ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Genome Wide

scholarly journals A practical approach to adjusting for population stratification in genome-wide association studies: principal components and propensity scores (PCAPS)

2018 ◽  
Vol 17 (6) ◽  
Author(s):  
Huaqing Zhao ◽  
Nandita Mitra ◽  
Peter A. Kanetsky ◽  
Katherine L. Nathanson ◽  
Timothy R. Rebbeck
Keyword(s):  
Principal Components ◽  
Population Stratification ◽  
Propensity Scores ◽  
Association Studies ◽  
Germ Cell Tumors ◽  
Gwas Data ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Testicular Germ Cell ◽  
Genome Wide

Abstract Genome-wide association studies (GWAS) are susceptible to bias due to population stratification (PS). The most widely used method to correct bias due to PS is principal components (PCs) analysis (PCA), but there is no objective method to guide which PCs to include as covariates. Often, the ten PCs with the highest eigenvalues are included to adjust for PS. This selection is arbitrary, and patterns of local linkage disequilibrium may affect PCA corrections. To address these limitations, we estimate genomic propensity scores based on all statistically significant PCs selected by the Tracy-Widom (TW) statistic. We compare a principal components and propensity scores (PCAPS) approach to PCA and EMMAX using simulated GWAS data under no, moderate, and severe PS. PCAPS reduced spurious genetic associations regardless of the degree of PS, resulting in odds ratio (OR) estimates closer to the true OR. We illustrate our PCAPS method using GWAS data from a study of testicular germ cell tumors. PCAPS provided a more conservative adjustment than PCA. Advantages of the PCAPS approach include reduction of bias compared to PCA, consistent selection of propensity scores to adjust for PS, the potential ability to handle outliers, and ease of implementation using existing software packages.

scholarly journals Multi-phenotype genome-wide association studies of the Norfolk Island isolate implicate pleiotropic loci involved in chronic kidney disease

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ngan K. Tran ◽  
Rodney A. Lea ◽  
Samuel Holland ◽  
Quan Nguyen ◽  
Arti M. Raghubar ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Kidney Function ◽  
Principal Components ◽  
Association Studies ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Functional Variants ◽  
Genome Wide ◽  
Norfolk Island

AbstractChronic kidney disease (CKD) is a persistent impairment of kidney function. Genome-wide association studies (GWAS) have revealed multiple genetic loci associated with CKD susceptibility but the complete genetic basis is not yet clear. Since CKD shares risk factors with cardiovascular diseases and diabetes, there may be pleiotropic loci at play but may go undetected when using single phenotype GWAS. Here, we used multi-phenotype GWAS in the Norfolk Island isolate (n = 380) to identify new loci associated with CKD. We performed a principal components analysis on different combinations of 29 quantitative traits to extract principal components (PCs) representative of multiple correlated phenotypes. GWAS of a PC derived from glomerular filtration rate, serum creatinine, and serum urea identified a suggestive peak (pmin = 1.67 × 10–7) that mapped to KCNIP4. Inclusion of other secondary CKD measurements with these three kidney function traits identified the KCNIP4 locus with GWAS significance (pmin = 1.59 × 10–9). Finally, we identified a group of two SNPs with increased minor allele frequencies as potential functional variants. With the use of genetic isolate and the PCA-based multi-phenotype GWAS approach, we have revealed a potential pleotropic effect locus for CKD. Further studies are required to assess functional relevance of this locus.

scholarly journals Comparing the Utility of Mitochondrial and Nuclear DNA to Adjust for Genetic Ancestry in Association Studies

Cells ◽  
2019 ◽  
Vol 8 (4) ◽  
pp. 306 ◽  
Author(s):  
◽  
Pinchas Cohen ◽  
◽  
◽  
◽  
...  
Keyword(s):  
Mitochondrial Dna ◽  
Principal Components ◽  
Nuclear Dna ◽  
Association Studies ◽  
Principal Component ◽  
Genetic Ancestry ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Ethnic Variation ◽  
Genome Wide

Mitochondrial genome-wide association studies identify mitochondrial single nucleotide polymorphisms (mtSNPs) that associate with disease or disease-related phenotypes. Most mitochondrial and nuclear genome-wide association studies adjust for genetic ancestry by including principal components derived from nuclear DNA, but not from mitochondrial DNA, as covariates in statistical regression analyses. Furthermore, there is no standard when controlling for genetic ancestry during mitochondrial and nuclear genetic interaction association scans, especially across ethnicities with substantial mitochondrial genetic heterogeneity. The purpose of this study is to (1) compare the degree of ethnic variation captured by principal components calculated from microarray-defined nuclear and mitochondrial DNA and (2) assess the utility of mitochondrial principal components for association studies. Analytic techniques used in this study include a principal component analysis for genetic ancestry, decision-tree classification for self-reported ethnicity, and linear regression for association tests. Data from the Health and Retirement Study, which includes self-reported White, Black, and Hispanic Americans, was used for all analyses. We report that (1) mitochondrial principal component analysis (PCA) captures ethnic variation to a similar or slightly greater degree than nuclear PCA in Blacks and Hispanics, (2) nuclear and mitochondrial DNA classify self-reported ethnicity to a high degree but with a similar level of error, and 3) mitochondrial principal components can be used as covariates to adjust for population stratification in association studies with complex traits, as demonstrated by our analysis of height—a phenotype with a high heritability. Overall, genetic association studies might reveal true and robust mtSNP associations when including mitochondrial principal components as regression covariates.

Principal components analysis corrects for stratification in genome-wide association studies

2006 ◽  
Vol 38 (8) ◽  
pp. 904-909 ◽  
Author(s):  
Alkes L Price ◽  
Nick J Patterson ◽  
Robert M Plenge ◽  
Michael E Weinblatt ◽  
Nancy A Shadick ◽  
...  
Keyword(s):  
Principal Components Analysis ◽  
Principal Components ◽  
Association Studies ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Genome Wide ◽  
Components Analysis
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