| Title: | Comprehensive whole-genome analyses of the UK Biobank reveal significant sex differences in both genotype missingness and allele frequency on the X chromosome |
| Journal: | Human Molecular Genetics |
| Published: | 9 Dec 2023 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/38073250/ |
| DOI: | https://doi.org/10.1093/hmg/ddad201 |
| URL: | https://academic.oup.com/hmg/advance-article-pdf/doi/10.1093/hmg/ddad201/54184522/ddad201.pdf |
Publication 9195
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Abstract
The UK Biobank is the most used dataset for genome-wide association studies (GWAS). GWAS of sex, essentially sex differences in minor allele frequencies (sdMAF), has identified autosomal SNPs with significant sdMAF, including in the UK Biobank, but the X chromosome was excluded. Our recent report identified multiple regions on the X chromosome with significant sdMAF, using short-read sequencing of other datasets. We performed a whole genome sdMAF analysis, with ~410 k white British individuals from the UK Biobank, using array genotyped, imputed or exome sequencing data. We observed marked sdMAF on the X chromosome, particularly at the boundaries between the pseudo-autosomal regions (PAR) and the non-PAR (NPR), as well as throughout the NPR, consistent with our earlier report. A small fraction of autosomal SNPs also showed significant sdMAF. Using the centrally imputed data, which relied mostly on low-coverage whole genome sequence, resulted in 2.1% of NPR SNPs with significant sdMAF. The whole exome sequencing also displays sdMAF on the X chromosome, including some NPR SNPs with heterozygous genotype calls in males. Genotyping, sequencing and imputation of X chromosomal SNPs requires further attention to ensure the integrity for downstream association analysis.</p>
5 Authors
- Desmond Zeya Chen
- Delnaz Roshandel
- Zhong Wang
- Lei Sun
- Andrew D Paterson
1 Application
| Application ID | Title |
|---|---|
| 48839 | Evaluating the effects of coding variation in inflammatory genes in cardio-metabolic disease |
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