| Title |
Evidence for epistasis between SLC6A4 and ITGB3 in autism etiology and in the determination of platelet serotonin levels
|
|---|---|
| Published in |
Human Genetics, January 2007
|
| DOI | 10.1007/s00439-006-0301-3 |
| Pubmed ID | |
| Authors |
Ana M. Coutinho, Inês Sousa, Madalena Martins, Catarina Correia, Teresa Morgadinho, Celeste Bento, Carla Marques, Assunção Ataíde, Teresa S. Miguel, Jason H. Moore, Guiomar Oliveira, Astrid M. Vicente |
| Abstract |
Autism is a neurodevelopmental disorder of unclear etiology. The consistent finding of platelet hyperserotonemia in a proportion of patients and its heritability within affected families suggest that genes involved in the serotonin system play a role in this disorder. The role in autism etiology of seven candidate genes in the serotonin metabolic and neurotransmission pathways and mapping to autism linkage regions (SLC6A4, HTR1A, HTR1D, HTR2A, HTR5A, TPH1 and ITGB3) was analyzed in a sample of 186 nuclear families. The impact of interactions among these genes in autism was assessed using the multifactor-dimensionality reduction (MDR) method in 186 patients and 181 controls. We further evaluated whether the effect of specific gene variants or gene interactions associated with autism etiology might be mediated by their influence on serotonin levels, using the quantitative transmission disequilibrium test (QTDT) and the restricted partition method (RPM), in a sample of 109 autistic children. We report a significant main effect of the HTR5A gene in autism (P = 0.0088), and a significant three-locus model comprising a synergistic interaction between the ITGB3 and SLC6A4 genes with an additive effect of HTR5A (P < 0.0010). In addition to the previously reported contribution of SLC6A4, we found significant associations of ITGB3 haplotypes with serotonin level distribution (P = 0.0163). The most significant models contributing to serotonin distribution were found for interactions between TPH1 rs4537731 and SLC6A4 haplotypes (P = 0.002) and between HTR1D rs6300 and SLC6A4 haplotypes (P = 0.013). In addition to the significant independent effects, evidence for interaction between SLC6A4 and ITGB3 markers was also found. The overall results implicate SLC6A4 and ITGB3 gene interactions in autism etiology and in serotonin level determination, providing evidence for a common underlying genetic mechanism and a molecular explanation for the association of platelet hyperserotonemia with autism. |
Mendeley readers
The data shown below were compiled from readership statistics for 108 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 3 | 3% |
| Brazil | 2 | 2% |
| Netherlands | 1 | <1% |
| Germany | 1 | <1% |
| Croatia | 1 | <1% |
| Unknown | 100 | 93% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 27 | 25% |
| Researcher | 22 | 20% |
| Student > Master | 9 | 8% |
| Student > Bachelor | 6 | 6% |
| Professor | 6 | 6% |
| Other | 18 | 17% |
| Unknown | 20 | 19% |
| Readers by discipline | Count | As % |
|---|---|---|
| Agricultural and Biological Sciences | 26 | 24% |
| Medicine and Dentistry | 17 | 16% |
| Neuroscience | 9 | 8% |
| Biochemistry, Genetics and Molecular Biology | 9 | 8% |
| Psychology | 9 | 8% |
| Other | 10 | 9% |
| Unknown | 28 | 26% |
Attention Score in Context
This research output has an Altmetric Attention Score of 9. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 24 October 2013.
All research outputs
#3,661,827
of 22,659,164 outputs
Outputs from Human Genetics
#363
of 2,948 outputs
Outputs of similar age
#16,591
of 156,759 outputs
Outputs of similar age from Human Genetics
#4
of 21 outputs
Altmetric has tracked 22,659,164 research outputs across all sources so far. Compared to these this one has done well and is in the 83rd percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 2,948 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.2. This one has done well, scoring higher than 87% of its peers.
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We're also able to compare this research output to 21 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 80% of its contemporaries.