Combinations of SNPs Related to Signal Transduction in Bipolar Disorder
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Combinations of SNPs Related to Signal Transduction in Bipolar Disorder. / Koefoed, Pernille; Andreassen, Ole A; Bennike, Bente; Dam, Henrik; Djurovic, Srdjan; Hansen, Thomas; Jorgensen, Martin Balslev; Kessing, Lars Vedel; Melle, Ingrid; Møller, Gert Lykke; Mors, Ole; Werge, Thomas; Mellerup, Erling.
In: P L o S One, Vol. 6, No. 8, 01.08.2011, p. e23812.Research output: Contribution to journal › Journal article › Research › peer-review
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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 - 2011/8/1
Y1 - 2011/8/1
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
VL - 6
SP - e23812
JO - PLoS ONE
JF - PLoS ONE
SN - 1932-6203
IS - 8
ER -
ID: 34335101