Sex-specific genetic architecture of whole blood serotonin levels
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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.
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Linkage studies in ASD have implicated the 17q11.2 region containing Slc6a4.
“linkage studies in ASD have implicated the 17q11.2 region containing Slc6a4 [50, 51].”
From Serotonin as a link between the gut-brain-microbiome axis in autism spectrum disorders (2018) · cites this paper as [50]
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- Authors
- Weiss, L. A., Abney, M., Cook, E. H., & Ober, C.
- Affiliations
- University of Chicago (US)
- Corresponding author
- Ober, Carole
- Venue
- The American Journal of Human Genetics
- Publisher
- Elsevier BV
- Published
- 2005-01
- Volume
- 76
- Issue
- 1
- Pages
- 33-41
- ISSN
- 0002-9297 (ISSN-L)
- PMC
- PMC1196431
- OpenAlex
- W2126589263
- Cited by
- 137
- References
- 46
- Citations by year
- 2025: 2 · 2024: 4 · 2023: 2 · 2022: 6 · 2021: 3 · 2020: 4 · 2019: 6 · 2018: 5 · 2017: 7 · 2016: 6 · 2015: 6 · 2014: 7 · 2013: 9 · 2012: 5
- FWCI
- 6.07
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- The American Journal of Human Genetics (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Science Foundation
- National Heart, Lung, and Blood Institute (P50HL056399, R01HL066533, HL66533, HL-56399)
- National Human Genome Research Institute (HG02899, R01HG002899)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK 55889, R01DK055889)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (U19HD035482, HD35482, P01HD035482)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Mapping and Diversity in Plants and Animals
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- whole blood serotonin, sexual dimorphism, quantitative trait loci, founder populations, heritability, CD61, serotonin transporter gene, chromosome 17q, chromosome 2q, chromosome 6q, chromosome 12q, chromosome 16p
- MeSH terms
- Adolescent, Adult, Aged, Child, Child, Preschool, Chromosome Mapping, Female, Humans, Genetic Linkage, Male, Middle Aged, Serotonin, Sex Characteristics, Founder Effect, Microsatellite Repeats, Quantitative Trait, Heritable
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