Cargando…

Estimating heritability and genetic correlations from large health datasets in the absence of genetic data

Typically, estimating genetic parameters, such as disease heritability and between-disease genetic correlations, demands large datasets containing all relevant phenotypic measures and detailed knowledge of family relationships or, alternatively, genotypic and phenotypic data for numerous unrelated i...

Descripción completa

Detalles Bibliográficos
Autores principales: Jia, Gengjie, Li, Yu, Zhang, Hanxin, Chattopadhyay, Ishanu, Boeck Jensen, Anders, Blair, David R., Davis, Lea, Robinson, Peter N., Dahlén, Torsten, Brunak, Søren, Benson, Mikael, Edgren, Gustaf, Cox, Nancy J., Gao, Xin, Rzhetsky, Andrey
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6890770/
https://www.ncbi.nlm.nih.gov/pubmed/31796735
http://dx.doi.org/10.1038/s41467-019-13455-0
_version_ 1783475681800224768
author Jia, Gengjie
Li, Yu
Zhang, Hanxin
Chattopadhyay, Ishanu
Boeck Jensen, Anders
Blair, David R.
Davis, Lea
Robinson, Peter N.
Dahlén, Torsten
Brunak, Søren
Benson, Mikael
Edgren, Gustaf
Cox, Nancy J.
Gao, Xin
Rzhetsky, Andrey
author_facet Jia, Gengjie
Li, Yu
Zhang, Hanxin
Chattopadhyay, Ishanu
Boeck Jensen, Anders
Blair, David R.
Davis, Lea
Robinson, Peter N.
Dahlén, Torsten
Brunak, Søren
Benson, Mikael
Edgren, Gustaf
Cox, Nancy J.
Gao, Xin
Rzhetsky, Andrey
author_sort Jia, Gengjie
collection PubMed
description Typically, estimating genetic parameters, such as disease heritability and between-disease genetic correlations, demands large datasets containing all relevant phenotypic measures and detailed knowledge of family relationships or, alternatively, genotypic and phenotypic data for numerous unrelated individuals. Here, we suggest an alternative, efficient estimation approach through the construction of two disease metrics from large health datasets: temporal disease prevalence curves and low-dimensional disease embeddings. We present eleven thousand heritability estimates corresponding to five study types: twins, traditional family studies, health records-based family studies, single nucleotide polymorphisms, and polygenic risk scores. We also compute over six hundred thousand estimates of genetic, environmental and phenotypic correlations. Furthermore, we find that: (1) disease curve shapes cluster into five general patterns; (2) early-onset diseases tend to have lower prevalence than late-onset diseases (Spearman’s ρ = 0.32, p < 10(–16)); and (3) the disease onset age and heritability are negatively correlated (ρ = −0.46, p < 10(–16)).
format Online
Article
Text
id pubmed-6890770
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-68907702019-12-05 Estimating heritability and genetic correlations from large health datasets in the absence of genetic data Jia, Gengjie Li, Yu Zhang, Hanxin Chattopadhyay, Ishanu Boeck Jensen, Anders Blair, David R. Davis, Lea Robinson, Peter N. Dahlén, Torsten Brunak, Søren Benson, Mikael Edgren, Gustaf Cox, Nancy J. Gao, Xin Rzhetsky, Andrey Nat Commun Article Typically, estimating genetic parameters, such as disease heritability and between-disease genetic correlations, demands large datasets containing all relevant phenotypic measures and detailed knowledge of family relationships or, alternatively, genotypic and phenotypic data for numerous unrelated individuals. Here, we suggest an alternative, efficient estimation approach through the construction of two disease metrics from large health datasets: temporal disease prevalence curves and low-dimensional disease embeddings. We present eleven thousand heritability estimates corresponding to five study types: twins, traditional family studies, health records-based family studies, single nucleotide polymorphisms, and polygenic risk scores. We also compute over six hundred thousand estimates of genetic, environmental and phenotypic correlations. Furthermore, we find that: (1) disease curve shapes cluster into five general patterns; (2) early-onset diseases tend to have lower prevalence than late-onset diseases (Spearman’s ρ = 0.32, p < 10(–16)); and (3) the disease onset age and heritability are negatively correlated (ρ = −0.46, p < 10(–16)). Nature Publishing Group UK 2019-12-03 /pmc/articles/PMC6890770/ /pubmed/31796735 http://dx.doi.org/10.1038/s41467-019-13455-0 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Jia, Gengjie
Li, Yu
Zhang, Hanxin
Chattopadhyay, Ishanu
Boeck Jensen, Anders
Blair, David R.
Davis, Lea
Robinson, Peter N.
Dahlén, Torsten
Brunak, Søren
Benson, Mikael
Edgren, Gustaf
Cox, Nancy J.
Gao, Xin
Rzhetsky, Andrey
Estimating heritability and genetic correlations from large health datasets in the absence of genetic data
title Estimating heritability and genetic correlations from large health datasets in the absence of genetic data
title_full Estimating heritability and genetic correlations from large health datasets in the absence of genetic data
title_fullStr Estimating heritability and genetic correlations from large health datasets in the absence of genetic data
title_full_unstemmed Estimating heritability and genetic correlations from large health datasets in the absence of genetic data
title_short Estimating heritability and genetic correlations from large health datasets in the absence of genetic data
title_sort estimating heritability and genetic correlations from large health datasets in the absence of genetic data
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6890770/
https://www.ncbi.nlm.nih.gov/pubmed/31796735
http://dx.doi.org/10.1038/s41467-019-13455-0
work_keys_str_mv AT jiagengjie estimatingheritabilityandgeneticcorrelationsfromlargehealthdatasetsintheabsenceofgeneticdata
AT liyu estimatingheritabilityandgeneticcorrelationsfromlargehealthdatasetsintheabsenceofgeneticdata
AT zhanghanxin estimatingheritabilityandgeneticcorrelationsfromlargehealthdatasetsintheabsenceofgeneticdata
AT chattopadhyayishanu estimatingheritabilityandgeneticcorrelationsfromlargehealthdatasetsintheabsenceofgeneticdata
AT boeckjensenanders estimatingheritabilityandgeneticcorrelationsfromlargehealthdatasetsintheabsenceofgeneticdata
AT blairdavidr estimatingheritabilityandgeneticcorrelationsfromlargehealthdatasetsintheabsenceofgeneticdata
AT davislea estimatingheritabilityandgeneticcorrelationsfromlargehealthdatasetsintheabsenceofgeneticdata
AT robinsonpetern estimatingheritabilityandgeneticcorrelationsfromlargehealthdatasetsintheabsenceofgeneticdata
AT dahlentorsten estimatingheritabilityandgeneticcorrelationsfromlargehealthdatasetsintheabsenceofgeneticdata
AT brunaksøren estimatingheritabilityandgeneticcorrelationsfromlargehealthdatasetsintheabsenceofgeneticdata
AT bensonmikael estimatingheritabilityandgeneticcorrelationsfromlargehealthdatasetsintheabsenceofgeneticdata
AT edgrengustaf estimatingheritabilityandgeneticcorrelationsfromlargehealthdatasetsintheabsenceofgeneticdata
AT coxnancyj estimatingheritabilityandgeneticcorrelationsfromlargehealthdatasetsintheabsenceofgeneticdata
AT gaoxin estimatingheritabilityandgeneticcorrelationsfromlargehealthdatasetsintheabsenceofgeneticdata
AT rzhetskyandrey estimatingheritabilityandgeneticcorrelationsfromlargehealthdatasetsintheabsenceofgeneticdata