117 research outputs found

    Probing the Association between Early Evolutionary Markers and Schizophrenia

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    <div><p>Schizophrenia is suggested to be a by-product of the evolution in humans, a compromise for our language, creative thinking and cognitive abilities, and thus, essentially, a human disorder. The time of its origin during the course of human evolution remains unclear. Here we investigate several markers of early human evolution and their relationship to the genetic risk of schizophrenia. We tested the schizophrenia evolutionary hypothesis by analyzing genome-wide association studies of schizophrenia and other human phenotypes in a statistical framework suited for polygenic architectures. We analyzed evolutionary proxy measures: human accelerated regions, segmental duplications, and ohnologs, representing various time periods of human evolution for overlap with the human genomic loci associated with schizophrenia. Polygenic enrichment plots suggest a higher prevalence of schizophrenia associations in human accelerated regions, segmental duplications and ohnologs. However, the enrichment is mostly accounted for by linkage disequilibrium, especially with functional elements like introns and untranslated regions. Our results did not provide clear evidence that markers of early human evolution are more likely associated with schizophrenia. While SNPs associated with schizophrenia are enriched in HAR, Ohno and SD regions, the enrichment seems to be mediated by affiliation to known genomic enrichment categories. Taken together with previous results, these findings suggest that schizophrenia risk may have mainly developed more recently in human evolution.</p></div

    Combinations of genetic variants associated with bipolar disorder

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    <div><p>The main objective of the study was to find genetic variants that in combination are significantly associated with bipolar disorder. In previous studies of bipolar disorder, combinations of three and four single nucleotide polymorphisms (SNP) genotypes taken from 803 SNPs were analyzed, and five clusters of combinations were found to be significantly associated with bipolar disorder. In the present study, combinations of ten SNP genotypes taken from the same 803 SNPs were analyzed, and one cluster of combinations was found to be significantly associated with bipolar disorder. Combinations from the new cluster and from the five previous clusters were identified in the genomes of 266 or 44% of the 607 patients in the study whereas none of the 1355 control participants had any of these combinations in their genome.The SNP genotypes in the smaller combinations were the normal homozygote, heterozygote or variant homozygote. In the combinations containing 10 SNP genotypes almost all the genotypes were the normal homozygote. Such a finding may indicate that accumulation in the genome of combinations containing few SNP genotypes may be a risk factor for bipolar disorder when those combinations contain relatively many rare SNP genotypes, whereas combinations need to contain many SNP genotypes to be a risk factor when most of the SNP genotypes are the normal homozygote.</p></div

    Combinations of Genetic Data Present in Bipolar Patients, but Absent in Control Persons

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    <div><p>The main objective of the study was to find combinations of genetic variants significantly associated with bipolar disorder. In a previous study of bipolar disorder, combinations of three single nucleotide polymorphism (SNP) genotypes taken from 803 SNPs were analyzed, and four clusters of combinations were found to be significantly associated with bipolar disorder. In the present study, combinations of four SNP genotypes taken from the same 803 SNPs were analyzed, and one cluster of combinations was found to be significantly associated with bipolar disorder. Combinations from the new cluster and from the four previous clusters were identified in the genomes of 209 of the 607 patients in the study whereas none of the 1355 control participants had any of these combinations in their genome.</p></div

    Accuracy and response time by conditions in the emotional faces task.

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    <p>Accuracy and response time by conditions in the emotional faces task.</p

    Stratified Q-Q plots and true discovery rates show consistency of enrichment.

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    <p><i>Upper panel:</i> Stratified Q-Q plots illustrating consistent enrichment of genic annotation categories across diverse phenotypes: (A) Height, (B) Schizophrenia (SCZ), and (C) Cigarettes per Day (CPD). All figures are corrected for inflation using intergenic inflation control. Only nominal p-values below the standard genome-wide significance threshold (p<5√ó10<sup>‚ąí8</sup>) are shown. <i>Lower panel:</i> Stratified True Discovery Rate (TDR) plots illustrating the increase in TDR associated with increased enrichment in (D) Height, (E) SCZ and (F) CPD. Genic annotation categories were: 5‚Ä≤ untranslated region (5‚Ä≤UTR), Exon, Intron, 3‚Ä≤ untranslated region (3‚Ä≤UTR), All SNPs, in addition to Intergenic.</p

    Extracellular potential profile with and without extracellular diffusion.

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    <p><b>(A)</b> Tissue subdivided into 15 sub-volumes. <b>(B-C)</b> Distribution of electrical potential <i>V</i> over the depth of the piece of tissue for the situation where diffusion was assumed to be zero <b>(B)</b>, and for the situation with diffusion included <b>(B)</b>. The variables were low-pass filtered by taking the temporal average over the time intervals indicated in the legend. To facilitate direct comparison, the (constant) <i>V</i>-profile for the case without diffusion was also plotted in <b>(C)</b>.</p

    Replication proportions and predicted replication probabilities.

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    <p>Local fdr estimate are shown on the x-axis (binned from 0 to 1 in increments of 0.10), with discovery fdr computed on 26 randomly selected sub-studies in the PGC schizophrenia data consisting of 17,691 cases and 24,683 controls on <i>N</i> = 129,973 SNPs pruned to pairwise LD ‚ȧ 0:20. For the independent replication sample we computed the meta-analysis <i>z</i>-scores using the remaining 26 studies, with 17,785 cases and 22,156 controls. Replication was defined as: (i) discovery and replication <i>z</i>-scores have same sign, and (ii) replication <i>z</i>-score associated with one-tailed <i>p</i>-value ‚ȧ 0:05. Black squares show actual replication proportions for each bin, whereas red squares show mean predicted replication probabilities given in <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005717#pgen.1005717.e087" target="_blank">Eq (15)</a>.</p
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