Variants Near FOXE1 Are Associated with Hypothyroidism and Other Thyroid Conditions: Using Electronic Medical Records for Genome- and Phenome-wide Studies

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Variants Near FOXE1 Are Associated with Hypothyroidism and Other Thyroid Conditions: Using Electronic Medical Records for Genome- and Phenome-wide Studies Joshua C. Denny, Dana C. Crawford, Marylyn D. Ritchie, Suzette J. Bielinski, Melissa A. Basford, Yuki Bradford, High Seng Chai, Lisa Bastarache, Rebecca Zuvich, Peggy Peissig, David Carrell, Andrea H. Ramirez, Jyotishman Pathak, Russell A. Wilke, Luke Rasmussen, Xiaoming Wang, Jennifer A. Pacheco, Abel N. Kho, M. Geoffrey Hayes, Noah Weston, Martha Matsumoto, Peter A. Kopp, Katherine M. Newton, Gail P. Jarvik, Rongling Li, Teri A. Manolio, Iftikhar J. Kullo, Christopher G. Chute, Rex L. Chisholm, Eric B. Larson, Catherine A. McCarty, Daniel R. Masys, Dan M. Roden, Mariza de Andrade The American Journal of Human Genetics Volume 89, Issue 4, Pages 529-542 (October 2011) DOI: 10.1016/j.ajhg.2011.09.008 Copyright © 2011 The American Society of Human Genetics Terms and Conditions

Figure 1 Genome-wide Association Analysis of Individuals with Primary Hypothyroidism versus Controls SNP tests of association (logistic regression) under the assumption of an additive genetic model adjusted for sex, birth decade, and study site; the tests incorporated 522,164 SNPs. The red horizontal line indicates p = 5 × 10−8, the threshold for genome-wide significance. The American Journal of Human Genetics 2011 89, 529-542DOI: (10.1016/j.ajhg.2011.09.008) Copyright © 2011 The American Society of Human Genetics Terms and Conditions

Figure 2 Regional Associations Near FOXE1 The American Journal of Human Genetics 2011 89, 529-542DOI: (10.1016/j.ajhg.2011.09.008) Copyright © 2011 The American Society of Human Genetics Terms and Conditions

Figure 3 Manhattan Plot of Phenome-wide Association Study for rs965513 The PheWAS considered 866 phenotypes via single SNP tests of association (logistic regression) adjusted for age and sex. The red line indicates Bonferroni significance for these associations, p = 5.8 × 10−5. The blue line indicates p = 0.05. For labeled associations, the dot size varies by the magnitude of the odds ratio. For purposes of display, we normalized all odds ratios by taking the multiplicative absolute value such that all values were greater than 1 (e.g., an odds ratio of 0.5 becomes 2). The American Journal of Human Genetics 2011 89, 529-542DOI: (10.1016/j.ajhg.2011.09.008) Copyright © 2011 The American Society of Human Genetics Terms and Conditions