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Research Paper|Volume 5, Issue 9|pp 704—716

QTL mapping of leukocyte telomere length in American Indians: The Strong Heart Family Study

Yun Zhu1, V. Saroja Voruganti2, Jue Lin3, Tet Matsuguchi3, Elizabeth Blackburn3, Lyle G. Best4, Elisa T. Lee5, Jean W. MacCluer2, Shelley A. Cole2, Jinying Zhao1
  • 1Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA 70112, USA;
  • 2Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX 78227, USA;
  • 3Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94143, USA;
  • 4Missouri Breaks Industries Research Inc., Timber Lake, SD 7625, USA;
  • 5Center for American Indian Health Research, University of Oklahoma Health Science Center, Oklahoma City, OK 73104; USA

* * Equal contribution

Received: August 21, 2013Accepted: September 9, 2013Published: September 11, 2013
https://doi.org/10.18632/aging.100600

Copyright: © 2013 Zhu et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Telomeres play a central role in cellular senescence and are associated with a variety of age-related disorders such as dementia, Alzheimer's disease and atherosclerosis. Telomere length varies greatly among individuals of the same age, and is heritable. Here we performed a genome-wide linkage scan to identify quantitative trait loci (QTL) influencing leukocyte telomere length (LTL) measured by quantitative PCR in 3,665 American Indians (aged 14 – 93 years) from 94 large, multi-generational families. All participants were recruited by the Strong Heart Family Study (SHFS), a prospective study to identify genetic factors for cardiovascular disease and its risk factors in American Indians residing in Oklahoma, Arizona and Dakota. LTL heritability was estimated to be between 51% and 62%, suggesting a strong genetic predisposition to interindividual variation of LTL in this population. Significant QTLs were localized to chromosome 13 (Logarithm of odds score (LOD) = 3.9) at 13q12.11, to 18q22.2 (LOD = 3.2) and to 3p14.1 (LOD = 3.0) for Oklahoma. This is the first study to identify susceptibility loci influencing leukocyte telomere variation in American Indians, a minority group suffering from a disproportionately high rate of type 2 diabetes and other age-related disorders.