Effects on gene expression and behavior of untagged short tandem repeats: the case of arginine vasopressin receptor 1a (AVPR1a) and externalizing behaviors
| Autor: | Barbara K. Lipska, Colin A. Hodgkinson, Primavera A. Spagnolo, Zhifeng Zhou, Clare Landefeld, David Goldman, Hui Sun, Pei-Hong Shen, Cheryl A. Marietta |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Male Receptors Vasopressin Genotype Gene Expression Single-nucleotide polymorphism Genome-wide association study Biology Polymorphism Single Nucleotide White People Article lcsh:RC321-571 Cohort Studies 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Gene Frequency Genetic variation SNP Humans Allele Allele frequency lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry Biological Psychiatry Finland Genetic association Genetics Haplotype Brain Psychiatry and Mental health 030104 developmental biology Haplotypes Attention Deficit and Disruptive Behavior Disorders Female 030217 neurology & neurosurgery Genome-Wide Association Study Microsatellite Repeats |
| Zdroj: | Translational Psychiatry, Vol 8, Iss 1, Pp 1-10 (2018) Translational Psychiatry |
| ISSN: | 2158-3188 |
| Popis: | Genome-wide association studies (GWAS) of complex, heritable, behavioral phenotypes have yielded an incomplete accounting of the genetic influences. The identified loci explain only a portion of the observed heritability, and few of the loci have been shown to be functional. It is clear that current GWAS techniques overlook key components of phenotypically relevant genetic variation, either because of sample size, as is frequently asserted, or because of methodology. Here we use arginine vasopressin receptor 1a (AVPR1a) as an in-depth model of a methodologic limitation of GWAS: the functional genetic variation (in the form of short tandem repeats) of this key gene involved in affiliative behavior cannot be captured by current GWAS methodologies. Importantly, we find evidence of differential allele expression, twofold or more, in at least a third of human brain samples heterozygous for a reporter SNP in the AVPR1a transcript. We also show that this functional effect and a downstream phenotype, externalizing behavior, are predicted by AVPR1a STRs but not SNPs. |
| Databáze: | OpenAIRE |
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