Cargando…

Relationships between estimated autozygosity and complex traits in the UK Biobank

Inbreeding increases the risk of certain Mendelian disorders in humans but may also reduce fitness through its effects on complex traits and diseases. Such inbreeding depression is thought to occur due to increased homozygosity at causal variants that are recessive with respect to fitness. Until rec...

Descripción completa

Detalles Bibliográficos
Autores principales: Johnson, Emma C., Evans, Luke M., Keller, Matthew C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6082573/
https://www.ncbi.nlm.nih.gov/pubmed/30052639
http://dx.doi.org/10.1371/journal.pgen.1007556
_version_ 1783345826189279232
author Johnson, Emma C.
Evans, Luke M.
Keller, Matthew C.
author_facet Johnson, Emma C.
Evans, Luke M.
Keller, Matthew C.
author_sort Johnson, Emma C.
collection PubMed
description Inbreeding increases the risk of certain Mendelian disorders in humans but may also reduce fitness through its effects on complex traits and diseases. Such inbreeding depression is thought to occur due to increased homozygosity at causal variants that are recessive with respect to fitness. Until recently it has been difficult to amass large enough sample sizes to investigate the effects of inbreeding depression on complex traits using genome-wide single nucleotide polymorphism (SNP) data in population-based samples. Further, it is difficult to infer causation in analyses that relate degree of inbreeding to complex traits because confounding variables (e.g., education) may influence both the likelihood for parents to outbreed and offspring trait values. The present study used runs of homozygosity in genome-wide SNP data in up to 400,000 individuals in the UK Biobank to estimate the proportion of the autosome that exists in autozygous tracts—stretches of the genome which are identical due to a shared common ancestor. After multiple testing corrections and controlling for possible sociodemographic confounders, we found significant relationships in the predicted direction between estimated autozygosity and three of the 26 traits we investigated: age at first sexual intercourse, fluid intelligence, and forced expiratory volume in 1 second. Our findings corroborate those of several published studies. These results may imply that these traits have been associated with Darwinian fitness over evolutionary time. However, some of the autozygosity-trait relationships were attenuated after controlling for background sociodemographic characteristics, suggesting that alternative explanations for these associations have not been eliminated. Care needs to be taken in the design and interpretation of ROH studies in order to glean reliable information about the genetic architecture and evolutionary history of complex traits.
format Online
Article
Text
id pubmed-6082573
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-60825732018-08-28 Relationships between estimated autozygosity and complex traits in the UK Biobank Johnson, Emma C. Evans, Luke M. Keller, Matthew C. PLoS Genet Research Article Inbreeding increases the risk of certain Mendelian disorders in humans but may also reduce fitness through its effects on complex traits and diseases. Such inbreeding depression is thought to occur due to increased homozygosity at causal variants that are recessive with respect to fitness. Until recently it has been difficult to amass large enough sample sizes to investigate the effects of inbreeding depression on complex traits using genome-wide single nucleotide polymorphism (SNP) data in population-based samples. Further, it is difficult to infer causation in analyses that relate degree of inbreeding to complex traits because confounding variables (e.g., education) may influence both the likelihood for parents to outbreed and offspring trait values. The present study used runs of homozygosity in genome-wide SNP data in up to 400,000 individuals in the UK Biobank to estimate the proportion of the autosome that exists in autozygous tracts—stretches of the genome which are identical due to a shared common ancestor. After multiple testing corrections and controlling for possible sociodemographic confounders, we found significant relationships in the predicted direction between estimated autozygosity and three of the 26 traits we investigated: age at first sexual intercourse, fluid intelligence, and forced expiratory volume in 1 second. Our findings corroborate those of several published studies. These results may imply that these traits have been associated with Darwinian fitness over evolutionary time. However, some of the autozygosity-trait relationships were attenuated after controlling for background sociodemographic characteristics, suggesting that alternative explanations for these associations have not been eliminated. Care needs to be taken in the design and interpretation of ROH studies in order to glean reliable information about the genetic architecture and evolutionary history of complex traits. Public Library of Science 2018-07-27 /pmc/articles/PMC6082573/ /pubmed/30052639 http://dx.doi.org/10.1371/journal.pgen.1007556 Text en © 2018 Johnson et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Johnson, Emma C.
Evans, Luke M.
Keller, Matthew C.
Relationships between estimated autozygosity and complex traits in the UK Biobank
title Relationships between estimated autozygosity and complex traits in the UK Biobank
title_full Relationships between estimated autozygosity and complex traits in the UK Biobank
title_fullStr Relationships between estimated autozygosity and complex traits in the UK Biobank
title_full_unstemmed Relationships between estimated autozygosity and complex traits in the UK Biobank
title_short Relationships between estimated autozygosity and complex traits in the UK Biobank
title_sort relationships between estimated autozygosity and complex traits in the uk biobank
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6082573/
https://www.ncbi.nlm.nih.gov/pubmed/30052639
http://dx.doi.org/10.1371/journal.pgen.1007556
work_keys_str_mv AT johnsonemmac relationshipsbetweenestimatedautozygosityandcomplextraitsintheukbiobank
AT evanslukem relationshipsbetweenestimatedautozygosityandcomplextraitsintheukbiobank
AT kellermatthewc relationshipsbetweenestimatedautozygosityandcomplextraitsintheukbiobank