Biomedical subjects

Lisa J Martin

Publications and source records attributed to Lisa J Martin.

At least 19 recordsLinked to original sources

PubMed2026

Genetic variation in SLCO1B1 is associated with methotrexate intolerance symptoms in juvenile idiopathic arthritis patients.

Methotrexate (MTX) treatment of juvenile idiopathic arthritis (JIA) is complicated by severe intolerance in approximately 30% of patients. MTX intolerance typically presents as nausea (anticipatory and postdose), vomiting, and behavioral symptoms. Although genetic variants in SLCO1B1 have been associated with MTX toxicity in retrospective studies of inflammatory bowel disease, prospective evaluation of this relationship in JIA patients is lacking. This study examined SLCO1B1-MTX intolerance associations accounting for clinical covariates in a prospective observational cohort of patients receiving standard weekly MTX doses (5-25 mg/m2). We performed a zero-inflated Poisson analysis using forward stepwise inclusion of clinical covariates followed by SLCO1B1 alleles. Among 217 JIA patients who completed the MTX Intolerance Severity Score (MISS) survey at 6 ± 2 months post-MTX initiation, the cohort was predominantly female (69.1%), White (76.5%), and received supplementation with folic acid (70.5%). Over 30% of patients met the threshold for MTX intolerance (MISS ≥ 6), and 62.7% of patients reported any MTX intolerance symptoms (MISS > 0). The SLCO1B1*37 allele was associated with lower odds of MISS > 0 (odds ratio = 0.60, P = 0.046) and a lower reported MISS score (incidence rate ratio = 0.74, P < 0.001) among individuals with non-zero intolerance, suggesting protection from MTX intolerance symptoms. These associations were consistent in sensitivity analyses stratified by folic acid supplementation. Further validation of these findings is needed to support future pharmacogenetic-guided MTX dosing strategies, including evaluation of other SLCO1B1 alleles.

individualized medicine↗

PubMed2026

Sequencing and health data resource of children of African ancestry.

PURPOSE: Individuals who self-report as Black or African American are historically underrepresented in genome-wide studies of disease risk, a disparity particularly evident in pediatric disease research. To address this gap, Cincinnati Children's Hospital Medical Center (CCHMC) established a biorepository and developed a comprehensive DNA sequencing resource including 15,684 individuals who self-identified as African American or Black and received care at CCHMC. METHODS: Participants were enrolled through the CCHMC Discover Together Biobank and sequenced. Admixture analyses confirmed the genetic ancestry of the cohort, which was then linked to electronic medical records. RESULTS: Genome-wide genotypes from common variants accompanied by medical record-sourced data are available through the Genomic Information Commons. This data set performs well in genetic studies. Specifically, we replicated known associations in sickle-cell disorder (HBB, HGNC:4827, P = 4.05 × 10-148), anxiety (PLAAT3, HGNC:17825, P = 6.93 × 10-9), and asthma (PCDH15, HGNC:14674, P = 5.6 × 10-10), while also identifying novel loci associated with anxiety, asthma, and asthma severity. CONCLUSION: We present the acquisition and quality of genetic and disease-associated data and present an analytical framework for using this resource. In partnership with a community advisory council, we have codeveloped a valuable framework for data use and future research.

Adolescent↗

PubMed2007

Mammographic density and the risk and detection of breast cancer.

BACKGROUND: Extensive mammographic density is associated with an increased risk of breast cancer and makes the detection of cancer by mammography difficult, but the influence of density on risk according to method of cancer detection is unknown. METHODS: We carried out three nested case-control studies in screened populations with 1112 matched case-control pairs. We examined the association of the measured percentage of density in the baseline mammogram with risk of breast cancer, according to method of cancer detection, time since the initiation of screening, and age. RESULTS: As compared with women with density in less than 10% of the mammogram, women with density in 75% or more had an increased risk of breast cancer (odds ratio, 4.7; 95% confidence interval [CI], 3.0 to 7.4), whether detected by screening (odds ratio, 3.5; 95% CI, 2.0 to 6.2) or less than 12 months after a negative screening examination (odds ratio, 17.8; 95% CI, 4.8 to 65.9). Increased risk of breast cancer, whether detected by screening or other means, persisted for at least 8 years after study entry and was greater in younger than in older women. For women younger than the median age of 56 years, 26% of all breast cancers and 50% of cancers detected less than 12 months after a negative screening test were attributable to density in 50% or more of the mammogram. CONCLUSIONS: Extensive mammographic density is strongly associated with the risk of breast cancer detected by screening or between screening tests. A substantial fraction of breast cancers can be attributed to this risk factor.

Adult↗

PubMed2007

Evidence in favor of linkage to human chromosomal regions 18q, 5q and 13q for bicuspid aortic valve and associated cardiovascular malformations.

The aim of this study was to identify regions of the genome that harbor genes influencing inheritance of bicuspid aortic valve (BAV) and/or associated cardiovascular malformation (CVM). Aortic valve disease is an important clinical problem, which often results in valve replacement, the second most common cardiac surgery in the United States. In every age group, a majority of cases of valve disease involves a BAV. BAV is the most common CVM with a reported prevalence of 1-2%. Heritability studies indicate that BAV determination is almost entirely genetic. We used a family-based genome-wide linkage analysis with microsatellite markers. Parametric and nonparametric analyses were performed with the software GENEHUNTER and SOLAR (Sequential Oligogenic Linkage Analysis Routines). Thirty-eight families (353 subjects) with BAV and/or associated CVM were assessed. Each participant underwent a standardized echocardiographic examination. The highest LOD score, 3.8, occurred on chromosome 18q between markers D18S68 and D18S1161. Two other chromosomal regions, 5q15-21 (between D5S644 and D5S2027) and 13q33-qter (between D13S1265 and 13qter), exhibited suggestive evidence of linkage (LOD > 2.0). Further, two previously reported linkage peaks on 9q34 and 17q24 were replicated in family specific analyses. No significant X chromosome linkage peaks were identified. In this genome-wide scan we demonstrate for the first time, that BAV and/or associated CVM exhibit linkage to chromosomes 18q, 5q and 13q. These regions likely contain genes whose mutation results in BAV and/or associated CVM indicating their important role in valvulogenesis and cardiac development.

Aortic Valve↗

PubMed2006

Linkage analysis for complex diseases using variance component analysis: SOLAR.

Variance component linkage analysis has become one of the most popular tools for the analysis of poly genic phenotypes. In particular for cardiovascular disease, such as coronary artery disease and myocardial infarction, variance component analysis holds some unique advantages. This analysis approach is versatile, affording the user the ability to incorporate the interplay between risk factors, genetic susceptibility, the effect of environmental factors, or the joint analysis of multiple phenotypes in the analysis. In this chapter, we present as an introduction the statistical background of variance component analysis as implemented in the genetic analysis package SOLAR.

Analysis of Variance↗

PubMed2006

Adiponectin is present in human milk and is associated with maternal factors.

BACKGROUND: Previous studies have shown that human milk has a role in the gastrointestinal, neural, and immune development of neonates. If present in milk, adiponectin would be a promising candidate for influencing infant development, given its metabolic functions. OBJECTIVES: Our objectives were to determine whether adiponectin is present in human milk and to characterize maternal factors associated with potential variation in milk adiponectin concentrations. DESIGN: We quantified adiponectin concentrations in human milk samples from donors to the Cincinnati Children's Research Human Milk Bank and randomly selected participants in a cohort study in Mexico City funded by the National Institutes of Health. Using cross-sectional and longitudinal data, we examined milk adiponectin concentrations in relation to lactation duration, maternal body mass index (BMI; in kg/m(2)), and ethnicity. RESULTS: Adiponectin was detected in human skim milk (range: 4.2-87.9 ng/mL). In cross-sectional and longitudinal analyses, duration of lactation was negatively associated with milk adiponectin concentrations (beta = -0.059 +/- 0.024 and -0.059 +/- 0.007, respectively; P < 0.02 for both). Maternal postpregnancy BMI was positively associated with milk adiponectin concentrations (beta = 0.08 +/- 0.02, P < 0.0001; longitudinal analysis). Mexican mothers had lower median milk adiponectin concentrations at 1 mo than did the non-Hispanic white subjects from Cincinnati (11.5 and 19.8 ng/mL; P = 0.003). CONCLUSIONS: Adiponectin is present in human milk and its concentrations are associated with duration of lactation, maternal adiposity, and ethnicity. Given the importance of adiponectin in inflammation, insulin sensitivity, and fatty acid metabolism, future studies should examine milk adiponectin's role in infant metabolic development.

Adiponectin↗

PubMed2006

Intervention with a low-fat, high-carbohydrate diet does not influence the timing of menopause.

BACKGROUND: Later age at menopause is associated with a greater risk of breast cancer. Dietary factors may at least partially influence breast cancer risk through an effect on the age at menopause. OBJECTIVE: We studied the effect of a low-fat, high-carbohydrate (LFHC) dietary intervention on the timing of menopause in women with greater risk of breast cancer. DESIGN: The study population included participants from an LFHC dietary intervention trial for the prevention of breast cancer in women with extensive mammographic density, a strong risk factor for breast cancer. Women who were premenopausal at baseline (n = 2611) were followed for an average of 7 y for menopause. Survival analysis was used to compare the time to menopause between the LFHC and control groups and to assess other factors associated with age at menopause. RESULTS: The LFHC intervention did not affect the time to natural menopause overall (P = 0.72 for log-rank test comparing study groups; n = 699 events). An observed interaction between study group and baseline body mass index (BMI; P = 0.01) indicated that the intervention group experienced earlier menopause than did the control group when BMI was low and that a higher BMI was associated with later menopause in the intervention group only. Greater parity, weight, and education were associated with later menopause, and greater age at first birth and baseline smoking were associated with earlier menopause. CONCLUSIONS: Overall, the LFHC dietary intervention did not influence the timing of menopause. Factors associated with age at menopause in this population were consistent with those reported in other populations.

Body Mass Index↗

PubMed2006

Mammographic density as a surrogate marker for the effects of hormone therapy on risk of breast cancer.

BACKGROUND: Some types of hormone therapy increase both risk of breast cancer and mammographic density, a risk factor for the disease, suggesting that mammographic density may be a surrogate marker for the effects of hormones on risk of breast cancer. This research was undertaken to determine whether the effect of hormone therapy on breast cancer risk is mediated by its effect on mammographic density. METHODS: Individually matched cases and controls from three nested case-control studies in breast screening populations were studied. Cases had developed invasive breast cancer at least 12 months after the initial screen. Information was collected on hormone use and other risk factors at the time of the baseline mammogram, and percent density was measured by a computer-assisted method. RESULTS: There were 1,748 postmenopausal women, of whom 426 (24.4%) were using hormones at the time of their initial screening mammogram. Current use of hormone therapy was associated with an increased risk of breast cancer (odds ratio, 1.26; 95% confidence interval, 1.0-1.6) that was little changed by adjustment for percent density in the baseline mammogram (odds ratio, 1.19; 95% confidence interval, 0.9-1.5). Percent density in the baseline mammogram was among cases greater in current users of hormones that in never-users (difference = 5.0%, P < 0.001), but the difference was smaller and nonsignificant in controls (difference = 1.6%, P = 0.3). CONCLUSION: Although the effects of hormone therapy on mammographic density were greater in cases than controls, we did not find evidence that these effects were causally related to risk of breast cancer.

Breast↗

PubMed2006

Body size, mammographic density, and breast cancer risk.

BACKGROUND: Greater weight and body mass index (BMI) are negatively correlated with mammographic density, a strong risk factor for breast cancer, and are associated with an increased risk of breast cancer in postmenopausal women, but with a reduced risk in premenopausal women. We have examined the associations of body size and mammographic density on breast cancer risk. METHOD: We examined the associations of body size and the percentage of mammographic density at baseline with subsequent risk of breast cancer among 1,114 matched case-control pairs identified from three screening programs. The effect of each factor on risk of breast cancer was examined before and after adjustment for the other, using logistic regression. RESULTS: In all subjects, before adjustment for mammographic density, breast cancer risk in the highest quintile of BMI, compared with the lowest, was 1.04 [95% confidence interval (CI), 0.8-1.4]. BMI was associated positively with breast cancer risk in postmenopausal women, and negatively in premenopausal women. After adjustment for density, the risk associated with BMI in all subjects increased to 1.60 (95% CI, 1.2-2.2), and was positive in both menopausal groups. Adjustment for BMI increased breast cancer risk in women with 75% or greater density, compared with 0%, increased from 4.25 (95% CI, 1.6-11.1) to 5.86 (95% CI, 2.2-15.6). CONCLUSION: BMI and mammographic density are independent risk factors for breast cancer, and likely to operate through different pathways. The strong negative correlated between them will lead to underestimation of the effects on risk of either pathway if confounding is not controlled.

Adult↗

PubMed2006

Mammographic density: a hormonally responsive risk factor for breast cancer.

Mammographic density refers to radiologically dense breast tissue, and reflects variations in the tissue composition of the breast. It is positively associated with collagen and epithelial and non-epithelial cells, and negatively associated with fat. There is extensive evidence that mammographic density is a risk factor for breast cancer, independent of other risk factors, and is associated with large relative and attributable risks for the disease. The epidemiology of mammographic density, notably the inverse association with age, is consistent with it being a marker of susceptibility to breast cancer. Cumulative exposure to mammographic density may be an important determinant of the age-specific incidence of breast cancer in the population. All risk factors for breast cancer must ultimately exert their influence by an effect on the breast, and these findings suggest that, for at least some risk factors, this influence includes an effect on the number of cells and the quantity of collagen in the breast, which is reflected in differences in mammographic density. Many of the genetic and environmental factors that influence the risk of breast cancer affect the proliferative activity and quantity of stromal and epithelial tissue in the breast, and these effects are reflected in differences in mammographic density among women of the same age. Some of these influences include endogenous and exogenous hormones, and the menopause. A better understanding of the factors that influence the response of breast tissue to these hormonal exposures may lead to an improved understanding of the aetiology of mammographic density and of breast cancer.

Age Factors↗

PubMed2006

Interactions between noncontiguous haplotypes in the adiponectin gene ACDC are associated with plasma adiponectin.

Adiponectin, an adipocyte protein important in insulin sensitization and cardioprotection, has a strong genetic component. We hypothesized that variants in the adiponectin gene (adipocyte collagen-domain containing [ACDC]) contribute to adiponectin levels in a biracial adolescent cohort. We genotyped 11 ACDC single nucleotide polymorphisms (SNPs) in 631 non-Hispanic white and 553 African-American unrelated adolescents in grades 5-12 randomly selected from the Princeton School District Study. ACDC SNPs -11,391 (A allele), -10,068 (G allele), and +276 (T allele) were associated with higher adiponectin, adjusting for sex, puberty stage, BMI Z score, and waist Z score. Contiguous two-SNP haplotypes of promoter variants -11,391/-10,068 were significantly associated with adiponectin levels in whites and African Americans (P < 0.0001 and 0.03, respectively). Extended haplotypes from the promoter through the second intron (-11,391 to +349) strongly associated with adiponectin in whites (P = 6 x 10(-11)) and African Americans (P = 0.004), but haplotypes of first intron SNPs -4,521 to -657 did not (P > 0.2). Noncontiguous haplotypes or interactions between two-SNP (-11,391/-10,068) and three-SNP (+45, +276, and +349) haplotypes predicted adiponectin better than either region alone. Variants of ACDC are associated with adiponectin levels in whites and African Americans. Interactions between noncontiguous ACDC haplotypes strongly influence adiponectin levels, suggesting nonadditive and potentially cis relationships between these regions.

Adiponectin↗

PubMed2005

Quantitative trait locus-specific genotype x alcoholism interaction on linkage for evoked electroencephalogram oscillations.

We explored the evidence for a quantitative trait locus (QTL)-specific genotype x alcoholism interaction for an evoked electroencephalogram theta band oscillation (ERP) phenotype on a region of chromosome 7 in participants of the US Collaborative Study on the Genetics of Alcoholism. Among 901 participants with both genotype and phenotype data available, we performed variance component linkage analysis (SOLAR version 2.1.2) in the full sample and stratified by DSM-III-R and Feighner-definite alcoholism categories. The heritability of the ERP phenotype after adjusting for age and sex effects in the combined sample and in the alcoholism classification sub-groups ranged from 40% to 66%. Linkage on chromosome 7 was identified at 158 cM (LOD = 3.8) in the full sample and at 108 in the non-alcoholic subgroup (LOD = 3.1). Further, we detected QTL-specific genotype x alcoholism interaction at these loci. This work demonstrates the importance of considering the complexity of common complex traits in our search for genes that predispose to alcoholism.

Alcoholism↗

PubMed2005

Accuracy of haplotype estimation in a region of low linkage disequilibrium.

We compared the accuracy of haplotype inferences at a 6 Mb region on chromosome 7 where significant linkage between a brain oscillation phenotype and a cholinergic muscarinic receptor gene was previously reported. Individual haplotype assignments and haplotype frequencies were estimated using 5, 10, and 14 consecutive Illumina single-nucleotide polymorphisms (SNPs) within the 1-LOD unit support interval of the chromosome 7 linkage peak. Initially, haplotypes were constructed incorporating phase information provided by relatives using the pedigree analysis package MERLIN. Population-based haplotypes were inferred using the haplotype estimation software HAPLO.STATS and PHASE, using unrelated individuals. The 14 SNPs within this region exhibited markedly low linkage disequilibrium, and the average D' estimate between SNPs was 0.18 (range: 0.01-0.97). In comparison to the family-based haplotypes calculated in MERLIN, the computational inferences of individual haplotype assignments were most accurate when considering 5 consecutive SNPs, but decayed dramatically when considering 10 or 14 SNPs in both PHASE and HAPLO.STATS. When comparing the two haplotype inference methods, both PHASE and HAPLO.STATS performed poorly. These analyses underscore the difficulties of haplotype estimation in the presence of low linkage disequilibrium and stress the importance of careful consideration of confidence measures when using estimated haplotype frequencies and individual assignments in biomedical research.

Family↗

PubMed2005

The relationships of adiponectin with insulin and lipids are strengthened with increasing adiposity.

CONTEXT: Adipose tissue inflammation has been implicated in the pathogenesis of obesity-related comorbidities. Adiponectin, an antiinflammatory protein, improves insulin sensitivity and lipid levels systemically. Because adiponectin is secreted by adipocytes, it may also act locally to counteract insulin resistance and dyslipidemia worsened by inflammation. OBJECTIVE: The aim of this study was to determine whether associations between adiponectin and insulin sensitivity and lipids are stronger with increasing adiposity. DESIGN: This cross-sectional study involved participants in The Princeton School District Study. SETTING: The study was conducted in the Princeton City schools (Cincinnati, OH) during the 2001-2002 school year. PARTICIPANTS: A total of 1196 non-Hispanic White and Black students in grades 5-12 participated. MAIN OUTCOME MEASURE: The relationships between adiponectin and high-density lipoprotein, triglycerides, and insulin were measured. To test our hypothesis, we: 1) compared correlation and regression coefficients of lean and nonlean individuals, and 2) incorporated an adiponectin by adiposity interaction in regression models. RESULTS: For high-density lipoprotein and triglycerides, the relationship with adiponectin, although present among lean adolescents, strengthened with increasing adiposity. However, with insulin, a relationship with adiponectin was only present among nonlean adolescents. CONCLUSIONS: These analyses suggest that adiponectin's relationship with insulin and lipids strengthens with increasing adiposity, such that heavier adolescents have a greater benefit from high levels of adiponectin than their lean counterparts.

Adiponectin↗

PubMed2005

Adolescent sex differences in adiponectin are conditional on pubertal development and adiposity.

OBJECTIVE: Adiponectin is an adipose tissue protein with important insulin-sensitizing, anti-inflammatory, and cardioprotective properties but is paradoxically lower in obese individuals. Sex differences in adiponectin have been reported in adults and adolescents but not in prepubertal children. In this study, we hypothesized that sex differences in adiponectin would develop during puberty and would be influenced by level of adiposity. RESEARCH METHODS AND PROCEDURES: Adiponectin levels were measured in 1196 white and African-American adolescents. Insulin resistance was estimated using the homeostasis model (HOMA-IR). Demographic, developmental, and metabolic variables, including interactions with adiposity measurements, were evaluated for independent relationships with adiponectin levels. RESULTS: Overall, adiponectin levels varied significantly by sex, race, adiposity, and puberty stage. Significant sex differences in adiponectin developed after the onset of puberty, particularly in lean adolescents. Adolescent boys had lower adiponectin levels in post-puberty compared with pre-puberty (p = 0.01) and had lower levels than girls in both puberty and post-puberty (both p < 0.001), after adjusting for race, BMI z-score, and natural logarithm-(HOMA-IR). Sex differences were also conditional on adiposity level, with significant sex differences among lean (p < 0.001) but not among non-lean (p = 0.16) adolescents. Adiponectin levels in girls decreased more with increasing adiposity than in boys (p = 0.004), but only marginally so after standardizing for girls' higher mean adiponectin level (p = 0.11). DISCUSSION: Sex differences in adiponectin are dependent on both puberty stage and adiposity in adolescents, such that by post-puberty, non-lean boys exhibit the lowest levels of adiponectin.

Adiponectin↗

PubMed2004

Evidence for a gene influencing fasting LDL cholesterol and triglyceride levels on chromosome 21q.

High levels of low-density lipoprotein (LDL) cholesterol, low levels of high-density lipoprotein (HDL) cholesterol, and high levels of triglycerides (TG) are strong predictors of cardiovascular disease risk. Motivated by previous evidence for pleiotropy between cholesterol and TG levels, we conducted bivariate linkage analysis of LDL cholesterol and TG concentration among participants of the Hypertension Genetic Epidemiolgy Network (HyperGEN), one of four networks in the NHLBI sponsored Family Blood Pressure Program Project. All available hypertensive siblings and their first-degree relatives were recruited. Both phenotypes were similarly adjusted for ethnicity, study center, sex, age, age-by-sex interactions, smoking, alcohol consumption, hormone use, diabetes medication use, and waist circumference. Variance component linkage analysis was performed as implemented in SOLAR, using ethnicity-specific marker allele frequencies derived from founders and multipoint IBDs calculated in MERLIN. A maximum genome-wide empirical LOD score of 3.9 was detected on chromosome 21 at 54cM, between markers D21S2055 and D21S1446. This signal overlaps with suggestive and/or significant linkages for total cholesterol, LDL cholesterol, and apolipoprotein B in three other studies and is suggestive of one or more genes on chromosome 21q jointly regulating LDL cholesterol and TG concentration.

Aged↗

PubMed2004

Bicuspid aortic valve is heritable.

OBJECTIVES: Previous studies have established familial clustering of bicuspid aortic valve (BAV), presumably indicating genetic inheritance. Our objective was to statistically test whether the segregation pattern of BAV is consistent with genetic inheritance and to obtain an estimate of the size of the genetic effect (heritability). BACKGROUND: Bicuspid aortic valve occurs in 1% of the population, making it the most common cardiovascular malformation (CVM). Bicuspid aortic valve is frequently an antecedent to aortic valve stenosis or insufficiency and is often associated with other CVMs, including aortic root dilation. The genetic and developmental significance of these findings remains obscure. METHODS: In 50 probands with BAV, we obtained a three-generation family history and echocardiograms on first-degree relatives. Heritability (h2) of BAV and BAV and/or other CVMs were estimated using maximum-likelihood-based variance decomposition extended to dichotomous traits implemented in the computer package Sequential Oligogenic Linkage Analysis Routines (SOLAR, San Antonio, Texas). RESULTS: A total of 309 probands and relatives participated. Bicuspid aortic valve was identified in 74 individuals (prevalence = 24%). A total of 97 individuals had BAV and/or other CVM (prevalence = 31%), including aortic coarctation, ventricular or atrial septal defect, abnormal mitral valve, aortic root dilation, or hypoplastic left heart syndrome. The heritability (h2) of BAV and BAV and/or other CVMs were 89% and 75%, respectively. CONCLUSIONS: The high heritability of BAV suggests that in this study population BAV determination is almost entirely genetic. The heritability of BAV plus other cardiovascular anomalies suggests that valve malformation can be primary to defective valvulogenesis or secondary to other elements of cardiogenesis.

Adolescent↗

PubMed2004

Genetics of monoamine metabolites in baboons: overlapping sets of genes influence levels of 5-hydroxyindolacetic acid, 3-hydroxy-4-methoxyphenylglycol, and homovanillic acid.

BACKGROUND: Monoamine neurotransmitters (serotonin, dopamine, and norepinephrine) are associated with several psychiatric disorders. Limited evidence suggests that monoamine levels are heritable, but no information concerning genetic relationships among monoamines is available. Further genetic analysis can help explain phenotypic correlations among monoamine levels and might eventually help identify genes involved in response to therapy or risk of psychopathology. METHODS: Levels of the monoamine metabolites homovanillic acid (HVA), 5-hydroxyindolacetic acid (5-HIAA), and 3-hydroxy-4-methoxyphenylglycol (MHPG) were measured in cerebrospinal fluid from 271 baboons (Papio hamadryas). Variance components methods were used to estimate heritabilities, and multivariate analyses were used to estimate genetic correlations (pleiotropy) and environmental correlations between metabolites. RESULTS: Each metabolite exhibited significant heritability in baboons (5-HIAA: h(2) =.30 +/-.17; MHPG: h(2) =.36 +/-.16; HVA: h(2) =.50 +/-.19). Multivariate analyses revealed genetic correlations between 5-HIAA and HVA and between HVA and MHPG. Environmental correlations were found between 5-HIAA and HVA and between 5-HIAA and MHPG. CONCLUSIONS: Overlapping, nonidentical sets of genes influence individual variation in 5-HIAA, MHPG, and HVA levels among baboons. The phenotypic correlation between 5-HIAA and HVA observed in nonhuman primates and humans is likely due to both shared genetic and environmental factors. Genetic analyses of monoamine levels in primates can provide novel information concerning the genetics of variation among humans.

Analysis of Variance↗