Genome wide association and exome sequence data analysis for more than 100 traits in Mexican Americans. J. E. Below1, B. E. Cade3, D. Aguilar2, E. Brown1, H. M. Highland1, S. Redline3,4, G. I. Bell5,6, N. J. Cox5,6, C. L. Hanis1 1) Epidemiology, Human Genetics & Environmental Sciences, University of Texas Health Science Center, Houston, TX; 2) Department of Medicine, Baylor College of Medicine, Houston, TX; 3) Division of Sleep Medicine, Brigham and Womens Hospital and Harvard Medical School, Boston, MA; 4) Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA; 5) Department of Medicine, The University of Chicago, Chicago, IL; 6) Department of Human Genetics, The University of Chicago, Chicago, IL.
As incidence of type 2 diabetes continues to rise in the United States unabated, the genetic epidemiology at play in Starr County Texas, where trends in the rates of type 2 diabetes and obesity have stayed approximately 30 years ahead of rest of the country, is of unprecedented relevance. We have now applied the fruits of decades of phenotypic measurements in a massive data analysis of more than 1400 Mexican Americans. In addition to more than 37 million tests of variation imputed from the latest release of 1000 genomes, we examined the complete exome sequence data, generated through our participation in the T2D-GENES consortium (U01 DK085501). We have identified more than 40 independent genome wide significant findings in traits ranging from uncorrelated to highly intertwined (Pearson's correlation: 0-0.98, median = .11). Together, these capture a much more complete picture of type 2 diabetes: from subclinical measures to a broad spectrum of untoward effects of impaired glucose control and comorbidities. Top findings ranged from measures of blood glucose control (rs190455070: p-value 2x10-9, rs181520960: 3x10-14) to biomarkers of cardiovascular health (rs74769851: 1x10-9 , LGAL3: <10-20) and measures of quality and duration of sleep (rs80125356: 2x10-16, rs78640598: 5x10-8, rs12424863: 1x10-9). We present findings from a number of traits never before genetically analyzed, including more than a dozen characteristics of infectious disease. Together these findings represent a concert of specific genetic and pleiotropic effects influencing a myriad set of immunological, inflammatory, cardiovascular, ocular, metabolic, and sleep related traits in a population undergoing an epidemic of obesity and diabetes.