Combinations of SNPs Related to Signal Transduction in Bipolar Disorder

TY - JOUR

T1 - Combinations of SNPs Related to Signal Transduction in Bipolar Disorder

AU - Koefoed, Pernille

AU - Andreassen, Ole A

AU - Bennike, Bente

AU - Dam, Henrik

AU - Djurovic, Srdjan

AU - Hansen, Thomas

AU - Jorgensen, Martin Balslev

AU - Kessing, Lars Vedel

AU - Melle, Ingrid

AU - Møller, Gert Lykke

AU - Mors, Ole

AU - Werge, Thomas

AU - Mellerup, Erling

PY - 2011/8/29

Y1 - 2011/8/29

N2 - 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.

AB - 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.

U2 - 10.1371/journal.pone.0023812

DO - 10.1371/journal.pone.0023812

M3 - Journal article

C2 - 21897858

SN - 1932-6203

VL - 6

SP - e23812

JO - PLoS Computational Biology

JF - PLoS Computational Biology

IS - 8

ER -