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. 2013 Aug 8;8(8):e72241.
doi: 10.1371/journal.pone.0072241. eCollection 2013.

Sex-specific heritability of spontaneous lipid levels in an extended pedigree of Indian-origin rhesus macaques (Macaca mulatta)

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Sex-specific heritability of spontaneous lipid levels in an extended pedigree of Indian-origin rhesus macaques (Macaca mulatta)

Amanda Vinson et al. PLoS One. .

Erratum in

  • PLoS One. 2014;9(1). doi:10.1371/annotation/1dc8bed5-aef7-4251-a23d-bded0b0ee9a4

Abstract

The rhesus macaque is an important model for human atherosclerosis but genetic determinants of relevant phenotypes have not yet been investigated in this species. Because lipid levels are well-established and heritable risk factors for human atherosclerosis, our goal was to assess the heritability of lipoprotein cholesterol and triglyceride levels in a single, extended pedigree of 1,289 Indian-origin rhesus macaques. Additionally, because increasing evidence supports sex differences in the genetic architecture of lipid levels and lipid metabolism in humans and macaques, we also explored sex-specific heritability for all lipid measures investigated in this study. Using standard methods, we measured lipoprotein cholesterol and triglyceride levels from fasted plasma in a sample of 193 pedigreed rhesus macaques selected for membership in large, paternal half-sib cohorts, and maintained on a low-fat, low cholesterol chow diet. Employing a variance components approach, we found moderate heritability for total cholesterol (h²=0.257, P=0.032), LDL cholesterol (h²=0.252, P=0.030), and triglyceride levels (h²=0.197, P=0.034) in the full sample. However, stratification by sex (N=68 males, N=125 females) revealed substantial sex-specific heritability for total cholesterol (0.644, P=0.004, females only), HDL cholesterol (0.843, P=0.0008, females only), VLDL cholesterol (0.482, P=0.018, males only), and triglyceride levels (0.705, P=0.001, males only) that was obscured or absent when sexes were combined in the full sample. We conclude that genes contribute to spontaneous variation in circulating lipid levels in the Indian-origin rhesus macaque in a sex-specific manner, and that the rhesus macaque is likely to be a valuable model for sex-specific genetic effects on lipid risk factors for human atherosclerosis. These findings are a first-ever report of heritability for cholesterol levels in this species, and support the need for expanded analysis of these traits in this population.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Frequency histogram of age by sex for all rhesus macaques in the single, 1,289-member pedigree described.
Figure 2
Figure 2. Frequency histogram of total, LDL-, HDL-, VLDLcholesterol and triglyceride levels in 193 rhesus macaques maintained on a low-fat, low-cholesterol diet.
Figure 3
Figure 3. Mean lipid levels across age categories for 125 female and 68 male pedigreed rhesus macaques.

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