Genome wide association analysis in a mouse advanced intercross line

Natalia M. Gonzales, Jungkyun Seo, Ana I. Hernandez Cordero, Celine L. St. Pierre, Jennifer S. Gregory, Margaret G. Distler, Mark Abney, Stefan Canzar, Arimantas Lionikas and Abraham A. Palmer ()
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Natalia M. Gonzales: University of Chicago
Jungkyun Seo: Duke University
Ana I. Hernandez Cordero: University of Aberdeen
Celine L. St. Pierre: Washington University School of Medicine
Jennifer S. Gregory: University of Aberdeen
Margaret G. Distler: University of California Los Angeles
Mark Abney: University of Chicago
Stefan Canzar: Ludwig-Maximilians-Universität München
Arimantas Lionikas: University of Aberdeen
Abraham A. Palmer: University of California San Diego

Nature Communications, 2018, vol. 9, issue 1, 1-12

Abstract: Abstract The LG/J x SM/J advanced intercross line of mice (LG x SM AIL) is a multigenerational outbred population. High minor allele frequencies, a simple genetic background, and the fully sequenced LG and SM genomes make it a powerful population for genome-wide association studies. Here we use 1,063 AIL mice to identify 126 significant associations for 50 traits relevant to human health and disease. We also identify thousands of cis- and trans-eQTLs in the hippocampus, striatum, and prefrontal cortex of ~200 mice. We replicate an association between locomotor activity and Csmd1, which we identified in an earlier generation of this AIL, and show that Csmd1 mutant mice recapitulate the locomotor phenotype. Our results demonstrate the utility of the LG x SM AIL as a mapping population, identify numerous novel associations, and shed light on the genetic architecture of mammalian behavior.

Date: 2018
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DOI: 10.1038/s41467-018-07642-8

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