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Detecting local genetic correlations with scan statistics

Genetic correlation analysis has quickly gained popularity in the past few years and provided insights into the genetic etiology of numerous complex diseases. However, existing approaches oversimplify the shared genetic architecture between different phenotypes and cannot effectively identify precis...

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Detalles Bibliográficos
Autores principales: Guo, Hanmin, Li, James J., Lu, Qiongshi, Hou, Lin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8016883/
https://www.ncbi.nlm.nih.gov/pubmed/33795679
http://dx.doi.org/10.1038/s41467-021-22334-6
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author Guo, Hanmin
Li, James J.
Lu, Qiongshi
Hou, Lin
author_facet Guo, Hanmin
Li, James J.
Lu, Qiongshi
Hou, Lin
author_sort Guo, Hanmin
collection PubMed
description Genetic correlation analysis has quickly gained popularity in the past few years and provided insights into the genetic etiology of numerous complex diseases. However, existing approaches oversimplify the shared genetic architecture between different phenotypes and cannot effectively identify precise genetic regions contributing to the genetic correlation. In this work, we introduce LOGODetect, a powerful and efficient statistical method to identify small genome segments harboring local genetic correlation signals. LOGODetect automatically identifies genetic regions showing consistent associations with multiple phenotypes through a scan statistic approach. It uses summary association statistics from genome-wide association studies (GWAS) as input and is robust to sample overlap between studies. Applied to seven phenotypically distinct but genetically correlated neuropsychiatric traits, we identify 227 non-overlapping genome regions associated with multiple traits, including multiple hub regions showing concordant effects on five or more traits. Our method addresses critical limitations in existing analytic strategies and may have wide applications in post-GWAS analysis.
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spelling pubmed-80168832021-04-16 Detecting local genetic correlations with scan statistics Guo, Hanmin Li, James J. Lu, Qiongshi Hou, Lin Nat Commun Article Genetic correlation analysis has quickly gained popularity in the past few years and provided insights into the genetic etiology of numerous complex diseases. However, existing approaches oversimplify the shared genetic architecture between different phenotypes and cannot effectively identify precise genetic regions contributing to the genetic correlation. In this work, we introduce LOGODetect, a powerful and efficient statistical method to identify small genome segments harboring local genetic correlation signals. LOGODetect automatically identifies genetic regions showing consistent associations with multiple phenotypes through a scan statistic approach. It uses summary association statistics from genome-wide association studies (GWAS) as input and is robust to sample overlap between studies. Applied to seven phenotypically distinct but genetically correlated neuropsychiatric traits, we identify 227 non-overlapping genome regions associated with multiple traits, including multiple hub regions showing concordant effects on five or more traits. Our method addresses critical limitations in existing analytic strategies and may have wide applications in post-GWAS analysis. Nature Publishing Group UK 2021-04-01 /pmc/articles/PMC8016883/ /pubmed/33795679 http://dx.doi.org/10.1038/s41467-021-22334-6 Text en © The Author(s) 2021 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
Guo, Hanmin
Li, James J.
Lu, Qiongshi
Hou, Lin
Detecting local genetic correlations with scan statistics
title Detecting local genetic correlations with scan statistics
title_full Detecting local genetic correlations with scan statistics
title_fullStr Detecting local genetic correlations with scan statistics
title_full_unstemmed Detecting local genetic correlations with scan statistics
title_short Detecting local genetic correlations with scan statistics
title_sort detecting local genetic correlations with scan statistics
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8016883/
https://www.ncbi.nlm.nih.gov/pubmed/33795679
http://dx.doi.org/10.1038/s41467-021-22334-6
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