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

Abstract

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.

Combinations of Genetic Variants Occurring Exclusively in Patients

“…However, in four studies of such combinations, no single combination was found to be significantly associated with the investigated disorder [7], [8], [10], [25]. Obviously, a combination that occurs only once in the study material will be present in either a patient or a control person, and such a combination will not be statistically significantly associated with a disorder.…”

“…Among the 607 bipolar patients, 73 had at least one of these combinations in their genomes. These combinations were not found in the genomes of any of the 1355 control persons [8].…”

“…Investigations of clusters of combinations occurring exclusively in patients have found that, although clusters are significantly associated with the disorder, individual combinations from these clusters do not show significant association with the disorder [7], [8], [10], [25]. These findings raise questions regarding the interpretation of a cluster of combinations that is significantly associated with a disorder.…”

“…Then the genetic variants with low p values can be paired with each other single variant to form two-variant combinations. This procedure can be repeated with the two-variant combinations to form three-variant combinations, and again with the three-variant combinations to generate four-variant combinations [8]. Similarly, biological criteria can be used to select single genetic variants of interest [9], which can then be used to form combinations with all of the variants.…”

“…Only 11 patients had combinations from two different clusters in their genome. A follow-up study investigated combinations of four SNP genotypes (summarized in Table 2), and found that a cluster containing 16 combinations was significantly associated with bipolar disorder [8]. A total of 73 patients showed some of these 16 combinations in their genomes, and 20 of these patients were also in one of the four above-described clusters with combinations of three SNP genotypes.…”