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Detecting Local Genetic Correlations with Scan Statistics

View ORCID ProfileHanmin Guo, View ORCID ProfileJames J. Li, View ORCID ProfileQiongshi Lu, View ORCID ProfileLin Hou
doi: https://doi.org/10.1101/808519
Hanmin Guo
1Center for Statistical Science, Tsinghua University, Beijing, China
2Department of Industrial Engineering, Tsinghua University, Beijing, China
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  • ORCID record for Hanmin Guo
James J. Li
3Department of Psychology, University of Wisconsin-Madison, Madison, WI, USA
4Waisman Center, University of Wisconsin-Madison, Madison, WI, USA
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Qiongshi Lu
5Department of Biostatistics and Medical Informatics, University of Wisconsin-Madison, Madison, WI, USA
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  • For correspondence: qlu@biostat.wisc.edu houl@tsinghua.edu.cn
Lin Hou
1Center for Statistical Science, Tsinghua University, Beijing, China
2Department of Industrial Engineering, Tsinghua University, Beijing, China
6MOE Key Laboratory of Bioinformatics, School of Life Sciences, Tsinghua University, Beijing, China
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  • For correspondence: qlu@biostat.wisc.edu houl@tsinghua.edu.cn
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Abstract

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 five phenotypically distinct but genetically correlated psychiatric disorders, we identified 49 non-overlapping genome regions associated with multiple disorders, including multiple hub regions showing concordant effects on more than two disorders. Our method addresses critical limitations in existing analytic strategies and may have wide applications in post-GWAS analysis.

Footnotes

  • ↵# These authors should be considered shared last author

  • https://github.com/ghm17/LOGODetect

  • http://www.med.unc.edu/pgc/downloads

  • http://genocanyon.med.yale.edu/GenoSkyline

  • https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE77565

  • http://resource.psychencode.org

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted October 31, 2019.
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Detecting Local Genetic Correlations with Scan Statistics
Hanmin Guo, James J. Li, Qiongshi Lu, Lin Hou
bioRxiv 808519; doi: https://doi.org/10.1101/808519
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Detecting Local Genetic Correlations with Scan Statistics
Hanmin Guo, James J. Li, Qiongshi Lu, Lin Hou
bioRxiv 808519; doi: https://doi.org/10.1101/808519

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