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Reply to: Genotype by sex interactions in ankylosing spondylitis

Nature Genetics volume 55, pages 17–18 (2023)Cite this article

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The Original Article was published on 09 January 2023

arising from: Bernabeu et al. Nature Genetics https://doi.org/10.1038/s41588-021-00912-0 (2021)

Differences between males and females have been described for a broad range of human complex traits, yet their underlying mechanisms are still poorly understood. In this context, our article1 provides an extensive and agnostic look into the role of the human genome, across 530 complex traits, making use of data originating from around half a million individuals from the UK Biobank. Our article constitutes an important first step, with further studies needed to, among others, assess causal associations and fine-map the genetic variants and regions reported. In their comment, Li et al.2 have begun this important task, performing a more detailed analysis of the locus linked to ankylosing spondylitis and, more specifically, the roles of the human leukocyte antigen (HLA) region genes HLA-B and MICA, which have been subject to previous debate3,4.

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Data availability

The data used pertain to the GTEx project v.8. Gene expression data are freely available at https://gtexportal.org/home/. GTEx genotype data are available on application through the database of Genotypes and Phenotypes. This research was conducted using the UK Biobank resource under project no. 788. The GTEx regulatory and consent protocols can be found at https://biospecimens.cancer.gov/resources/sops/library.asp.

Code availability

We used PLINK v.1.9 to run our eQTL analysis, which is freely available online at https://www.cog-genomics.org/plink2/. The custom Python code is openly available at Zenodo https://doi.org/10.5281/zenodo.7093777.

References

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Authors and Affiliations

  1. Institute of Genetics and Cancer, The University of Edinburgh, Edinburgh, UK

    Elena Bernabeu, Oriol Canela-Xandri & Albert Tenesa

  2. The Roslin Institute, Royal (Dick) School of Veterinary Studies, The University of Edinburgh, Edinburgh, UK

    Konrad Rawlik, Andrea Talenti, James Prendergast & Albert Tenesa

  3. Medical Research Council Human Genetics Unit, The University of Edinburgh, Edinburgh, UK

    Albert Tenesa

Authors
  1. Elena Bernabeu
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  2. Konrad Rawlik
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  3. Oriol Canela-Xandri
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  4. Andrea Talenti
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  5. James Prendergast
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  6. Albert Tenesa
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Contributions

E.B. drafted the primary text with input from K.R., J.P., A. Tenesa, O.C.-X. and A. Talenti. All authors reviewed and approved the final draft.

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Correspondence to Elena Bernabeu or Albert Tenesa.

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The authors declare no competing interests.

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Nature Genetics thanks Seunggeun Lee and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Supplementary Note containing Methods and Tables 1 and 2.

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Bernabeu, E., Rawlik, K., Canela-Xandri, O. et al. Reply to: Genotype by sex interactions in ankylosing spondylitis. Nat Genet 55, 17–18 (2023). https://doi.org/10.1038/s41588-022-01251-4

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