Rogers Jeffrey, Martin Lisa J, Comuzzie Anthony G, Mann J John, Manuck Stephen B, Leland Michelle, Kaplan Jay R
Department of Genetics, Southwest Foundation for Biomedical Research, San Antonio, Texas 78227, USA.
Biol Psychiatry. 2004 Apr 1;55(7):739-44. doi: 10.1016/j.biopsych.2003.12.017.
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.
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.
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.
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.
单胺神经递质(血清素、多巴胺和去甲肾上腺素)与多种精神疾病有关。有限的证据表明单胺水平具有遗传性,但尚无关于单胺之间遗传关系的信息。进一步的基因分析有助于解释单胺水平之间的表型相关性,并最终可能有助于识别参与治疗反应或精神病理学风险的基因。
测量了271只狒狒(阿拉伯狒狒)脑脊液中单胺代谢物高香草酸(HVA)、5-羟吲哚乙酸(5-HIAA)和3-羟基-4-甲氧基苯乙二醇(MHPG)的水平。采用方差成分法估计遗传力,并采用多变量分析估计代谢物之间的遗传相关性(多效性)和环境相关性。
每种代谢物在狒狒中均表现出显著的遗传力(5-HIAA:h(2)=.30±.17;MHPG:h(2)=.36±.16;HVA:h(2)=.50±.19)。多变量分析揭示了5-HIAA与HVA之间以及HVA与MHPG之间的遗传相关性。在5-HIAA与HVA之间以及5-HIAA与MHPG之间发现了环境相关性。
重叠但不完全相同的基因集影响狒狒中5-HIAA、MHPG和HVA水平的个体差异。在非人类灵长类动物和人类中观察到的5-HIAA与HVA之间的表型相关性可能是由于共同的遗传和环境因素。对灵长类动物单胺水平的基因分析可以提供有关人类变异遗传学的新信息。