Abstract
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.
Highlights
This study is the third study using a material of 607 bipolar patients and 1355 controls from Denmark and Norway in which 803 single nucleotide polymorphisms (SNP) in 55 genes were analyzed.In bipolar disorder hyperactivity is the main symptom of the manic phase, possibly reflecting faster signal transmission in the brain
Among the 803 SNPs no single SNP genotype and no single combination of the SNP genotypes was found to be significantly associated with bipolar disorder
No clusters of combinations of two SNP genotypes were found to be significantly associated with bipolar disorder
Summary
In bipolar disorder hyperactivity is the main symptom of the manic phase, possibly reflecting faster signal transmission in the brain Based on this assumption we have investigated genes related to the action potential, refractory period, ion channels and CNS myelination. Combinations of genetic variants met GLM who is a mathematician working with array mathematics and he became interested in the particular challenges regarding combinations, and started the company Genokey. The funder (the investors) provided support in the form of salary for GLM, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The affiliation of EM with Genokey has played a major role in study because GLM and EM have worked together with the analysis of the combinations of the genetic data The specific role of GLM is articulated in the ‘author contributions’ section.” The affiliation of EM with Genokey has played a major role in study because GLM and EM have worked together with the analysis of the combinations of the genetic data
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