How to Include Chromosome X in Your Genome‐Wide Association Study
Open accessAbstract
In current genome‐wide association studies (GWAS), the analysis is usually focused on autosomal variants only, and the sex chromosomes are often neglected. Recently, a number of technical hurdles have been described that add to a reluctance of including chromosome X in a GWAS, including complications in genotype calling, imputation, and selection of test statistics. To overcome this, we provide a “how to” guide for analyzing X chromosomal data within a standard GWAS. Following a general pipeline for GWAS, we highlight the steps in which the X chromosome requires specific attention, and we give tentative advice for each of these. Through this, we show that by selection of sensible algorithms and parameter settings, the inclusion of chromosome X in GWAS is manageable. Closing this gap is expected to further elucidate the genetic background of complex diseases, especially of those with sex‐specific features.
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Only called X-chromosome variants in UKB were included for X-chromosome analyses after X-chromosome-specific quality-control steps.
“We therefore included only the called X-chromosome variants in UKB for these analyses after performing X-chromosome-specific quality-control steps 38 .”
From Genome-wide association meta-analysis in 269,867 individuals identifies new genetic and functional links to intelligence (2018) · cites this paper as [38]
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Fast and accurate genotype imputation in genome-wide association studies through pre-phasing
Howie, B., Fuchsberger, C., Stephens, M., Marchini, J., & Abecasis, G. R. (2012) · Nature Genetics · doi:10.1038/ng.2354 · Cited by 1,737 · see citing works
The hemophilias--from royal genes to gene therapy
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New susceptibility locus for coronary artery disease on chromosome 3q22.3
Italian Atherosclerosis, T., Erdmann, J., Myocardial Infarction Genetics Consortium, Wellcome Trust Case Control Consortium, Cardiogenics Consortium, Großhennig, A., Braund, P. S., König, I. R., Hengstenberg, C., Hall, A. S., et al. (2009) · Nature Genetics · doi:10.1038/ng.307 · Cited by 484 · see citing works
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Savage, J. E., Jansen, P. R., Stringer, S., Watanabe, K., Bryois, J., de Leeuw, C. A., Nagel, M., Awasthi, S., Barr, P. B., Coleman, J. R. I., et al. (2018) · Nature Genetics · doi:10.1038/s41588-018-0152-6 · Cited by 1,443 · see citing works
- Authors
- König, I. R., Loley, C., Erdmann, J., & Ziegler, A.
- Affiliations
- University Hospital Schleswig-Holstein (DE)
- Institute for Integrative and Experimental Genomics (DE)
- Corresponding author
- König, Inke R.
- Venue
- Genetic Epidemiology
- Publisher
- Wiley
- Published
- 2014-01-09
- Volume
- 38
- Issue
- 2
- Pages
- 97-103
- ISSN
- 0741-0395 (ISSN-L)
- 1098-2272
- OpenAlex
- W2010227703
- Cited by
- 113
- References
- 4
- Citations by year
- 2026: 4 · 2025: 10 · 2024: 10 · 2023: 14 · 2022: 19 · 2021: 9 · 2020: 6 · 2019: 13 · 2018: 14 · 2017: 5 · 2016: 3 · 2015: 4 · 2014: 2
- FWCI
- 3.06
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Genetic Epidemiology (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- German Science Foundation (KO 2250/4-1)
- German Science Foundation and the German Federal Ministry of Education and Research (BMBF)
- German National Genome Research Network (01GS0417, 01GS0832)
- FP6 and FP7 EU (LSHM-CT-2006-037593)
- ENGAGE (201413)
- BMBF/ANR
- German Science Foundation Excellence Cluster “Inflammation (HEALTH-2011-278913)
- German Ministry of Education and Research (01KU0908A, 01KU0908B)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Mapping and Diversity in Plants and Animals
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Keywords
- X chromosome, sex chromosomes, genome-wide association study, genotype calling, imputation, test statistics, complex diseases, sex differences
- MeSH terms
- Algorithms, Female, Genotype, Humans, Male, Chromosomes, Human, X, Genome-Wide Association Study
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