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.
Rogers
Jeffrey
J
Department of Genetics, Southwest Foundation for Biomedical Research, San Antonio, Texas 78227, USA.
Martin
Lisa J
LJ
Comuzzie
Anthony G
AG
Mann
J John
JJ
Manuck
Stephen B
SB
Leland
Michelle
M
Kaplan
Jay R
JR
D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D005260:Female; D015870:Gene Expression / Q000502:physiology; D014644:Genetic Variation / Q000235:genetics; D005838:Genotype; D006719:Homovanillic Acid / Q000134:cerebrospinal fluid*; D006897:Hydroxyindoleacetic Acid / Q000134:cerebrospinal fluid*; D016013:Likelihood Functions; D008297:Male; D008426:Maternal Deprivation; D008734:Methoxyhydroxyphenylglycol / Q000134:cerebrospinal fluid*; D010215:Papio / Q000235:genetics*; D010641:Phenotype; D012016:Reference Values; D012931:Social Environment; D013045:Species Specificity
D008734:Methoxyhydroxyphenylglycol; D006897:Hydroxyindoleacetic Acid; D006719:Homovanillic Acid