Selection in the dopamine receptor 2 gene: New candidate SNPs for disease-related studies
- Published
- Accepted
- Subject Areas
- Anthropology, Bioinformatics, Evolutionary Studies, Genetics
- Keywords
- balancing selection, dopamine, DRD2, dopamine receptor 2, schizophrenia
- Copyright
- © 2015 Göllner et al.
- Licence
- This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. For attribution, the original author(s), title, publication source (PeerJ PrePrints) and either DOI or URL of the article must be cited.
- Cite this article
- 2015. Selection in the dopamine receptor 2 gene: New candidate SNPs for disease-related studies. PeerJ PrePrints 3:e1083v1 https://doi.org/10.7287/peerj.preprints.1083v1
Abstract
Dopamine is a major neurotransmitter in the human brain and is associated with various diseases. Schizophrenia, for example, is treated by blocking the dopamine receptors type 2. In 2009, Shaner, Miller and Mintz stated that schizophrenia was the low fitness variant of a highly variable mental trait. We therefore explore whether the dopamine receptor 2 gene (DRD2) underwent any selection processes. We acquired genotype data of the 1000 Genomes project (phase I), which contains 1093 individuals from 14 populations. We included only single nucleotide polymorphisms (SNPs) with a minor allele frequency (MAF) of over 0.05 in the analysis. This is equivalent to 151 SNPs for DRD2. We used two different approaches (an outlier approach and a Bayesian approach) to detect loci under selection. The combined results of both approaches yielded nine candidate SNPs under balancing selection. While directional selection strongly favours one allele over all others, balancing selection favours more than one allele. All candidates are in the intronic region of the gene and only one (rs12574471) has been mentioned in the literature. Two of our candidate SNPs are located in specific regions of the gene: rs80215768 lies within a promoter flanking region and rs74751335 lies within a transcription factor binding site. We strongly encourage research on our candidate SNPs and their possible phenotypic effects.
Author Comment
This is a submission to PeerJ for review.
Supplemental Information
List of SNPs that were excluded from LD calculation
Table S1. SNPs that caused the LD calculation of R to fail and thus were excluded from the LD calculation. IBS was excluded entirely because 30 SNPs were flawed (which is nearly 20% of all SNPs).
Full results of all SNPs
Table S2. Results for all 151 SNPs of DRD2. The left column shows the results of LOSITAN (see Figure 2 for the visual output). The right column the results of BayeScan (see Figure 3 for the visual output). P = P (Simulation FST < sample FST); He = expected heterozygosity; FST = Fixation Indices subpopulation to total population. P = posterior probability; log10 (PO) = logarithm (base 10) of the posterior odds; q-value = false discovery rate (FDR) analogue of the P value; αi = locus-specific component (negative alpha suggests balancing selection, while positive alpha suggests directional selection); FST = Fixation Indices subpopulation to total population. * - the value of 1000 means infinity (see BayeScan manual).
ASW heatmap
Figure S1. D’ heat map of the ASW population.
CEU heatmap
Figure S2. D’ heat map of the CEU population.
CHB heatmap
Figure S3. D’ heat map of the CHB population.
CHS heatmap
Figure S4. D’ heat map of the CHS population.
CLM heatmap
Figure S5. D’ heat map of the CLM population.
FIN heatmap
Figure S6. D’ heat map of the FIN population.
GBR heatmap
Figure S7. D’ heat map of the GBR population.
JPT heatmap
Figure S8. D’ heat map of the JPT population.
LWK heatmap
Figure S9. D’ heat map of the LWK population.
MXL heatmap
Figure S10. D’ heat map of the MXL population.
PUR heatmap
Figure S11. D’ heat map of the PUR population.
TSI heatmap
Figure S12. D’ heat map of the TSI population.
YRI heatmap
Figure S13. D’ heat map of the YRI population.