Dataset Information

Sex-specific genetic architecture of whole blood serotonin levels.

ABSTRACT: Recently, a quantitative-trait locus (QTL) for whole blood serotonin level was identified in a genomewide linkage and association study in a founder population. Because serotonin level is a sexually dimorphic trait, in the present study, we evaluated the sex-specific genetic architecture of whole blood serotonin level in the same population. Here, we use an extended homozygosity-by-descent linkage method that is suitable for large complex pedigrees. Although both males and females have high broad heritability (H2=0.99), females have a higher additive component (h2=0.63 in females; h2=0.27 in males). Furthermore, the serotonin QTL on 17q that was identified previously in this population, integrin beta 3 (ITGB3), and a novel locus on 2q influence serotonin levels only in males, whereas linkage to a region on chromosome 6q is specific to females. Both sexes contribute to linkage signals on 12q and 16p. There were, overall, more associations meeting criteria for suggestive significance in males than in females, including those of ITGB3 and the serotonin transporter gene (5HTT). This analysis is consistent with heritable sexual dimorphism in whole blood serotonin levels resulting from the effects of a combination of sex-specific and sex-independent loci.

SUBMITTER: Weiss LA

PROVIDER: S-EPMC1196431 | biostudies-literature | 2005 Jan

REPOSITORIES: biostudies-literature

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Sex-specific genetic architecture of whole blood serotonin levels.

Weiss Lauren A LA Abney Mark M Cook Edwin H EH Ober Carole C

American journal of human genetics 20041103 1

Recently, a quantitative-trait locus (QTL) for whole blood serotonin level was identified in a genomewide linkage and association study in a founder population. Because serotonin level is a sexually dimorphic trait, in the present study, we evaluated the sex-specific genetic architecture of whole blood serotonin level in the same population. Here, we use an extended homozygosity-by-descent linkage method that is suitable for large complex pedigrees. Although both males and females have high broa ...[more]

PMID: 15526234

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Project description:Simple Summary Attention deficit hyperactivity disorder (ADHD) is a relatively common neurodevelopmental disorder mainly affecting children and adolescents. ADHD is associated with significant social stigma, psychosocial adversities, and reduced working abilities. As with humans, dogs can suffer from ADHD-like behaviors, but to date, there are few studies on this condition in the canine species. Therefore, the present study analyzed the levels of serum serotonin and dopamine in dogs with signs that are similar to the ones presented in human patients with ADHD (compared to control dogs) that were assessed clinically and through different behavior scales. The results obtained indicate that both neurotransmitters have a tendency to be observed in lower concentrations in dogs presenting behavioral signs consistent with ADHD-like disorders. This finding may be useful for contributing to the study of the diagnosis and treatment of this disorder in dogs. ADHD-like associated behaviors can disrupt the normal coexistence of the dogs in their homes and contribute to abandonment, which continues to be a major social and animal welfare problem today. Abstract As with humans, dogs can suffer from attention deficit hyperactivity disorder-like (ADHD-like) behaviors naturally and exhibit high levels of hyperactivity/impulsivity and attention deficit problems, making the domestic dog a potential animal model for ADHD. ADHD has a very complex pathophysiology in which many neurotransmitters are involved, such as serotonin and dopamine. The aim of the study was to evaluate serum serotonin and dopamine levels in dogs with ADHD-like symptomatology. Fifty-eight dogs were studied, of which, thirty-six were classified as ADHD-like after physical and behavioral assessments. Additionally, the dogs’ owners performed a series of scientifically validated questionnaires which included C-BARQ, the Dog Impulsivity Assessment Scale, and the Dog-ADHD rating scale. Serum from every animal was collected after the behavioral assessments and analyzed with commercial ELISA tests for serotonin and dopamine determination. Kruskal–Wallis tests and Lasso regressions were applied to assess the relationships between both neurotransmitters and the ADHD-like behaviors (as assessed by clinical evaluation and through the different questionnaires). The dogs clinically classified as ADHD-like showed lower serotonin and dopamine concentrations. Further, serotonin and dopamine levels were also linked to aggression, hyperactivity, and impulsivity. Decreased serotonin concentrations were also related to fear, attachment, and touch sensitivity. Finally, it must be noted that our data suggested a strong relationship between serotonin and dopamine and ADHD-like behaviors.

Dataset Information

Sex-specific genetic architecture of whole blood serotonin levels.

Publications

Sex-specific genetic architecture of whole blood serotonin levels.

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