Heritability estimation of osteoarthritis in the pig-tailed macaque (Macaca nemestrina) with a look toward future data collection

Abstract

We examine heritability estimation of an ordinal trait for osteoarthritis, using a population of pig-tailed macaques from the Washington National Primate Research Center (WaNPRC). This estimation is non-trivial, as the data consist of ordinal measurements on 16 intervertebral spaces throughout each macaque’s spinal cord, with many missing values. We examine the resulting heritability estimates from different model choices, and also perform a simulation study to compare the performance of heritability estimation with these different models under specific known parameter values. Under both the real data analysis and the simulation study, we find that heritability estimates from an assumption of normality of the trait differ greatly from those of ordered probit regression, which considers the ordinality of the trait. This finding indicates that some caution should be observed regarding model selection when estimating heritability of an ordinal quantity. Furthermore, we find evidence that our real data have little information for valid heritability estimation under ordered probit regression. We thus conclude with an exploration of sample size requirements for heritability estimation under this model. For an ordinal trait, an incorrect assumption of normality can lead to severely biased heritability estimation. Sample size requirements for heritability estimation of an ordinal trait under the threshold model depends on the pedigree structure, trait distribution and the degree of relatedness between each phenotyped individual. Our sample of 173 monkeys did not have enough information from which to estimate heritability, but estimable heritability can be obtained with as few as 180 related individuals under certain scenarios examined here.

Quantitative genetic methods depending on the nature of the phenotypic trait

“…The availability of a wide variety of distributions is relevant for evolutionary biologists, as most evolutionary relevant traits have complex distributions. Such models have been used to study the genetics of various traits, such as dispersal, number of offspring, disease, resistance, and productivity …”

Heritability and relationship of oxytocin receptor gene variants with social behavior and central oxytocin in colony-reared adult female rhesus macaques

“…Heritability was not estimable for aggression, even after trying multiple distributions and stronger priors on σ 2 A This was most likely due to a combination of low occurrence of this behavior (i.e. low information) and a small sample size [15]. Because controlling for relatedness was essential for all models, this outcome was excluded from subsequent analyses.…”

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“…Etiology of osteoarthritis in primates is often uncertain, and may be the result of injury, disease, biochemistry, gender, and developmental abnormality; however, advanced age is perhaps the most prevalent condition associated with this disease (Chi et al, 2014;Duncan, Colman & Kramer, 2012;Ganz, 2003;Uno, 1997). Unlike most other mammals, primates have wideranging appendicular capabilities associated with a highly active lifestyle and an exceptionally long potential life-span (Larson et al, 2001).…”