Combinations of SNPs related to signal transduction in bipolar disorder.

Any given single nucleotide polymorphism (SNP) in a genome may have little or no functional impact. A biologically significant effect may possibly emerge only when a number of key SNP-related genotypes occur together in a single organism. Thus, in analysis of many SNPs in association studies of comp...

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Main Authors: Pernille Koefoed, Ole A Andreassen, Bente Bennike, Henrik Dam, Srdjan Djurovic, Thomas Hansen, Martin Balslev Jorgensen, Lars Vedel Kessing, Ingrid Melle, Gert Lykke Møller, Ole Mors, Thomas Werge, Erling Mellerup
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2011-01-01
Series:PLoS ONE
Online Access:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0023812&type=printable
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author Pernille Koefoed
Ole A Andreassen
Bente Bennike
Henrik Dam
Srdjan Djurovic
Thomas Hansen
Martin Balslev Jorgensen
Lars Vedel Kessing
Ingrid Melle
Gert Lykke Møller
Ole Mors
Thomas Werge
Erling Mellerup
author_facet Pernille Koefoed
Ole A Andreassen
Bente Bennike
Henrik Dam
Srdjan Djurovic
Thomas Hansen
Martin Balslev Jorgensen
Lars Vedel Kessing
Ingrid Melle
Gert Lykke Møller
Ole Mors
Thomas Werge
Erling Mellerup
author_sort Pernille Koefoed
collection DOAJ
description Any given single nucleotide polymorphism (SNP) in a genome may have little or no functional impact. A biologically significant effect may possibly emerge only when a number of key SNP-related genotypes occur together in a single organism. Thus, in analysis of many SNPs in association studies of complex diseases, it may be useful to look at combinations of genotypes. Genes related to signal transmission, e.g., ion channel genes, may be of interest in this respect in the context of bipolar disorder. In the present study, we analysed 803 SNPs in 55 genes related to aspects of signal transmission and calculated all combinations of three genotypes from the 3×803 SNP genotypes for 1355 controls and 607 patients with bipolar disorder. Four clusters of patient-specific combinations were identified. Permutation tests indicated that some of these combinations might be related to bipolar disorder. The WTCCC bipolar dataset were use for replication, 469 of the 803 SNP were present in the WTCCC dataset either directly (n = 132) or by imputation (n = 337) covering 51 of our selected genes. We found three clusters of patient-specific 3×SNP combinations in the WTCCC dataset. Different SNPs were involved in the clusters in the two datasets. The present analyses of the combinations of SNP genotypes support a role for both genetic heterogeneity and interactions in the genetic architecture of bipolar disorder.
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spelling doaj-art-cfec69e036ba47b783e0b5cda138b0312025-08-20T02:33:57ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-01-0168e2381210.1371/journal.pone.0023812Combinations of SNPs related to signal transduction in bipolar disorder.Pernille KoefoedOle A AndreassenBente BennikeHenrik DamSrdjan DjurovicThomas HansenMartin Balslev JorgensenLars Vedel KessingIngrid MelleGert Lykke MøllerOle MorsThomas WergeErling MellerupAny given single nucleotide polymorphism (SNP) in a genome may have little or no functional impact. A biologically significant effect may possibly emerge only when a number of key SNP-related genotypes occur together in a single organism. Thus, in analysis of many SNPs in association studies of complex diseases, it may be useful to look at combinations of genotypes. Genes related to signal transmission, e.g., ion channel genes, may be of interest in this respect in the context of bipolar disorder. In the present study, we analysed 803 SNPs in 55 genes related to aspects of signal transmission and calculated all combinations of three genotypes from the 3×803 SNP genotypes for 1355 controls and 607 patients with bipolar disorder. Four clusters of patient-specific combinations were identified. Permutation tests indicated that some of these combinations might be related to bipolar disorder. The WTCCC bipolar dataset were use for replication, 469 of the 803 SNP were present in the WTCCC dataset either directly (n = 132) or by imputation (n = 337) covering 51 of our selected genes. We found three clusters of patient-specific 3×SNP combinations in the WTCCC dataset. Different SNPs were involved in the clusters in the two datasets. The present analyses of the combinations of SNP genotypes support a role for both genetic heterogeneity and interactions in the genetic architecture of bipolar disorder.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0023812&type=printable
spellingShingle Pernille Koefoed
Ole A Andreassen
Bente Bennike
Henrik Dam
Srdjan Djurovic
Thomas Hansen
Martin Balslev Jorgensen
Lars Vedel Kessing
Ingrid Melle
Gert Lykke Møller
Ole Mors
Thomas Werge
Erling Mellerup
Combinations of SNPs related to signal transduction in bipolar disorder.
PLoS ONE
title Combinations of SNPs related to signal transduction in bipolar disorder.
title_full Combinations of SNPs related to signal transduction in bipolar disorder.
title_fullStr Combinations of SNPs related to signal transduction in bipolar disorder.
title_full_unstemmed Combinations of SNPs related to signal transduction in bipolar disorder.
title_short Combinations of SNPs related to signal transduction in bipolar disorder.
title_sort combinations of snps related to signal transduction in bipolar disorder
url https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0023812&type=printable
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