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Research Article
Irene Novo
Universidade de Vigo
Corresponding Author
ORCiD: https://orcid.org/0000-0001-7187-1872
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Recent studies have shown the ubiquity of pleiotropy for variants affecting human complex traits. These studies also show that rare variants tend to be less pleiotropic than common ones, suggesting that purifying natural selection acts against highly pleiotropic variants of large effect. Here we investigate the mean frequency, effect size and recombination rate associated with pleiotropic variants, and focus particularly on whether highly pleiotropic variants are enriched in regions with putative strong background selection. We evaluate variants for 41 human traits using data from the NHGRI-EBI GWAS Catalog, as well as data from other three studies. Our results show that variants involving a higher degree of pleiotropy tend to be more common, have larger mean effect sizes, and contribute more to heritability than variants with a lower degree of pleiotropy. Using data from four different studies, we show that more pleiotropic variants are enriched in genome regions with stronger background selection than less pleiotropic variants. Thus, we conclude that even though highly pleiotropic variants found so far have larger average effect sizes and frequencies than less pleiotropic ones, they are likely to be subjected to stronger background selection.
Keywords
SNPs, recombination, deleterious mutations, negative selection
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CURRENT STATUS: Under Revision
Version 1
Posted 24 Mar, 2021
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Editorial decision: Major revisions
On 01 May, 2021
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This preprint is under consideration at Human Genetics. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research Article
Irene Novo
Universidade de Vigo
Corresponding Author
ORCiD: https://orcid.org/0000-0001-7187-1872
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Under Revision
Version 1
Posted 24 Mar, 2021
No community comments so far
Editorial decision: Major revisions
On 01 May, 2021
Reviews received
Received 05 Apr, 2021
Editor assigned
On 19 Mar, 2021
Reviewers invited
Invitations sent on 19 Mar, 2021
First submitted
On 18 Mar, 2021
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Recent studies have shown the ubiquity of pleiotropy for variants affecting human complex traits. These studies also show that rare variants tend to be less pleiotropic than common ones, suggesting that purifying natural selection acts against highly pleiotropic variants of large effect. Here we investigate the mean frequency, effect size and recombination rate associated with pleiotropic variants, and focus particularly on whether highly pleiotropic variants are enriched in regions with putative strong background selection. We evaluate variants for 41 human traits using data from the NHGRI-EBI GWAS Catalog, as well as data from other three studies. Our results show that variants involving a higher degree of pleiotropy tend to be more common, have larger mean effect sizes, and contribute more to heritability than variants with a lower degree of pleiotropy. Using data from four different studies, we show that more pleiotropic variants are enriched in genome regions with stronger background selection than less pleiotropic variants. Thus, we conclude that even though highly pleiotropic variants found so far have larger average effect sizes and frequencies than less pleiotropic ones, they are likely to be subjected to stronger background selection.
Figure 1
Figure 2
Figure 3
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