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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.

INTRODUCTION: We sought to determine the differences in pregnancy outcomes among white, black, Hispanic, Asian/Pacific Islander, Native American women with bipolar disorder. METHODS: A retrospective cohort of 3,344 women with bipolar disorder and singleton, non-anomalous gestations was used to examine maternal and neonatal outcomes, assessed according to race. Maternal outcomes included gestational diabetes (GDM), chorioamnionitis, postpartum hemorrhage (PPH), and preeclampsia/eclampsia (abbreviated “Any PET”). Neonatal outcomes included preterm birth (divided into <37, <34 and <32 weeks gestational age), respiratory distress syndrome (RDS), and jaundice. Multivariate regression analyses and chi-square tests were employed for statistical comparisons and a p-value of less than 0.05 was used to indicate statistical significance. RESULTS: Compared to white women, and after controlling for confounders, Asian/Pacific Islander women were more likely to develop GDM, and chorioamnionitis, and trended towards higher rates of PPH. Additionally, black women trended towards higher rates of PET. Compared to neonates of white women, neonates of black women were more likely to be delivered preterm before 37, 34, and 32 weeks gestational age, and had higher rates of RDS. Additionally, Asian/Pacific Islander neonates trended towards higher rates of jaundice. CONCLUSION: Pregnancies of non-white women with bipolar disorder are associated with higher rates of obstetric and neonatal complications than pregnancies of white women, with specific complications and rates varying across races. This data may suggest disparities exist in management of pregnant women with bipolar disorder across different races.

Objective: While the metabolic consequences of obesity have been studied extensively in the rhesus macaque, corollary genetic studies of obesity are non-existent. Here, we assess genetic contributions to spontaneous adiposity in this species. Methods: We assessed phenotypic variation by age-class and sex for body mass index, waist-to-height ratio, waist-to-thigh ratio, and waist circumference in 583 macaques. We estimated total and sex-specific heritability for all traits, including waist-to-thigh ratio adjusted for BMI, as well as genotypic and phenotypic correlations. We also assessed functional genetic variation at BDNF , FTO , LEP , LEPR , MC4R , PCSK1 , POMC , and SIM1 in 4 animals with extreme spontaneous adiposity. Results: Trait heritability in the combined sample was low-to-moderate (0.14–0.32), while sex-specific heritability was more substantial (0.20–0.67). Heritability was greater in females for all traits except BMI. All traits were robustly correlated, with genetic correlations of 0.63–0.93 indicating substantial pleiotropy. We discovered likely functional variants in the 4 macaques at all 8 human obesity genes, including 6 missense mutations in BDNF , FTO , LEP , LEPR , and PCSK1 , and notably, 1 nonsense mutation in LEPR . Conclusions: We find a moderate polygenic contribution to adiposity in rhesus macaques, and mutations with potentially larger effects in multiple genes that influence obesity in humans.