Strategies for Processing and Quality Control of Illumina Genotyping Arrays

Overview

Journal Brief Bioinform

Publisher Oxford University Press

Specialty Biology

Date 2017 Mar 24

PMID 28334151

Citations 36

Authors

Shilin Zhao

Wang Jing

David C Samuels

Quanghu Sheng

Yu Shyr

Yan Guo

Affiliations

Soon will be listed here.

Abstract

Illumina genotyping arrays have powered thousands of large-scale genome-wide association studies over the past decade. Yet, because of the tremendous volume and complicated genetic assumptions of Illumina genotyping data, processing and quality control (QC) of these data remain a challenge. Thorough QC ensures the accurate identification of single-nucleotide polymorphisms and is required for the correct interpretation of genetic association results. By processing genotyping data on > 100 000 subjects from >10 major Illumina genotyping arrays, we have accumulated extensive experience in handling some of the most peculiar scenarios related to the processing and QC of Illumina genotyping data. Here, we describe strategies for processing Illumina genotyping data from the raw data to an analysis ready format, and we elaborate on the necessary QC procedures required at each processing step. High-quality Illumina genotyping data sets can be obtained by following our detailed QC strategies.

Citing Articles

Transcriptional impacts of substance use disorder and HIV on human ventral midbrain neurons and microglia.

Wilson A, Jacobs M, Lambert T, Valada A, Meloni G, Gilmore E bioRxiv. 2025; .

PMID: 39974894 PMC: 11838593. DOI: 10.1101/2025.02.05.636667.

GWAS links to neuropsychiatric symptoms in mild cognitive impairment and dementia.

Vattathil S, Blostein F, Miller-Fleming T, Davis L, Wingo T, Wingo A medRxiv. 2025; .

PMID: 39974048 PMC: 11838693. DOI: 10.1101/2025.01.31.25321498.

PGSXplorer: an integrated nextflow pipeline for comprehensive quality control and polygenic score model development.

Yaras T, Oktay Y, Karakulah G PeerJ. 2025; 13:e18973.

PMID: 39959831 PMC: 11829630. DOI: 10.7717/peerj.18973.

A brain DNA co-methylation network analysis of psychosis in Alzheimer's disease.

Kouhsar M, Weymouth L, Smith A, Imm J, Bredemeyer C, Wedatilake Y Alzheimers Dement. 2025; 21(2):e14501.

PMID: 39936280 PMC: 11815327. DOI: 10.1002/alz.14501.

Severe COVID-19 disease is associated with genetic factors affecting plasma ACE2 receptor and CRP concentrations.

Vogi V, Haschka D, Forer L, Schwendinger S, Petzer V, Coassin S Sci Rep. 2025; 15(1):4708.

PMID: 39922945 PMC: 11807156. DOI: 10.1038/s41598-025-89306-4.

References

Wang Z, Gerstein M, Snyder M . RNA-Seq: a revolutionary tool for transcriptomics. Nat Rev Genet. 2008; 10(1):57-63. PMC: 2949280. DOI: 10.1038/nrg2484. View

Hindorff L, Sethupathy P, Junkins H, Ramos E, Mehta J, Collins F . Potential etiologic and functional implications of genome-wide association loci for human diseases and traits. Proc Natl Acad Sci U S A. 2009; 106(23):9362-7. PMC: 2687147. DOI: 10.1073/pnas.0903103106. View

Price A, Patterson N, Plenge R, Weinblatt M, Shadick N, Reich D . Principal components analysis corrects for stratification in genome-wide association studies. Nat Genet. 2006; 38(8):904-9. DOI: 10.1038/ng1847. View

Anderson C, Pettersson F, Clarke G, Cardon L, Morris A, Zondervan K . Data quality control in genetic case-control association studies. Nat Protoc. 2010; 5(9):1564-73. PMC: 3025522. DOI: 10.1038/nprot.2010.116. View

Abecasis G, Auton A, Brooks L, DePristo M, Durbin R, Handsaker R . An integrated map of genetic variation from 1,092 human genomes. Nature. 2012; 491(7422):56-65. PMC: 3498066. DOI: 10.1038/nature11632. View

Cloonan N, Forrest A, Kolle G, Gardiner B, Faulkner G, Brown M . Stem cell transcriptome profiling via massive-scale mRNA sequencing. Nat Methods. 2008; 5(7):613-9. DOI: 10.1038/nmeth.1223. View

Hosking L, Lumsden S, Lewis K, Yeo A, McCarthy L, Bansal A . Detection of genotyping errors by Hardy-Weinberg equilibrium testing. Eur J Hum Genet. 2004; 12(5):395-9. DOI: 10.1038/sj.ejhg.5201164. View

Meyre D, Delplanque J, Chevre J, Lecoeur C, Lobbens S, Gallina S . Genome-wide association study for early-onset and morbid adult obesity identifies three new risk loci in European populations. Nat Genet. 2009; 41(2):157-9. DOI: 10.1038/ng.301. View

Wittke-Thompson J, Pluzhnikov A, Cox N . Rational inferences about departures from Hardy-Weinberg equilibrium. Am J Hum Genet. 2005; 76(6):967-86. PMC: 1196455. DOI: 10.1086/430507. View

10.

Marioni J, Mason C, Mane S, Stephens M, Gilad Y . RNA-seq: an assessment of technical reproducibility and comparison with gene expression arrays. Genome Res. 2008; 18(9):1509-17. PMC: 2527709. DOI: 10.1101/gr.079558.108. View

11.

Guo Y, Ye F, Sheng Q, Clark T, Samuels D . Three-stage quality control strategies for DNA re-sequencing data. Brief Bioinform. 2013; 15(6):879-89. PMC: 4492405. DOI: 10.1093/bib/bbt069. View

12.

Nelson S, Doheny K, Laurie C, Mirel D . Is 'forward' the same as 'plus'?…and other adventures in SNP allele nomenclature. Trends Genet. 2012; 28(8):361-3. PMC: 6099125. DOI: 10.1016/j.tig.2012.05.002. View

13.

Zhang P, Samuels D, Zhao S, Wang J, Shyr Y, Guo Y . Practicability of mitochondrial heteroplasmy detection through an Illumina genotyping array. Mitochondrion. 2016; 31:75-78. DOI: 10.1016/j.mito.2016.08.018. View

14.

Wang K, Li M, Bucan M . Pathway-based approaches for analysis of genomewide association studies. Am J Hum Genet. 2007; 81(6):1278-83. PMC: 2276352. DOI: 10.1086/522374. View

15.

Han L, Vickers K, Samuels D, Guo Y . Alternative applications for distinct RNA sequencing strategies. Brief Bioinform. 2014; 16(4):629-39. PMC: 4542857. DOI: 10.1093/bib/bbu032. View

16.

Turner S, Armstrong L, Bradford Y, Carlson C, Crawford D, Crenshaw A . Quality control procedures for genome-wide association studies. Curr Protoc Hum Genet. 2011; Chapter 1:Unit1.19. PMC: 3066182. DOI: 10.1002/0471142905.hg0119s68. View

17.

Gomes I, Collins A, Lonjou C, Thomas N, Wilkinson J, Watson M . Hardy-Weinberg quality control. Ann Hum Genet. 2001; 63(Pt 6):535-8. DOI: 10.1017/S0003480099007824. View

18.

Samuels D, Wang J, Ye F, He J, Levinson R, Sheng Q . Heterozygosity Ratio, a Robust Global Genomic Measure of Autozygosity and Its Association with Height and Disease Risk. Genetics. 2016; 204(3):893-904. PMC: 5105867. DOI: 10.1534/genetics.116.189936. View

19.

Sheng Q, Vickers K, Zhao S, Wang J, Samuels D, Koues O . Multi-perspective quality control of Illumina RNA sequencing data analysis. Brief Funct Genomics. 2016; 16(4):194-204. PMC: 5860075. DOI: 10.1093/bfgp/elw035. View

20.

Wang J, Raskin L, Samuels D, Shyr Y, Guo Y . Genome measures used for quality control are dependent on gene function and ancestry. Bioinformatics. 2014; 31(3):318-23. PMC: 4308666. DOI: 10.1093/bioinformatics/btu668. View