The estrogen hypothesis of schizophrenia implicates glucose metabolism: association study in three independent samples

TY - JOUR

T1 - The estrogen hypothesis of schizophrenia implicates glucose metabolism

T2 - association study in three independent samples

AU - Olsen, Line

AU - Hansen, Thomas

AU - Jakobsen, Klaus D

AU - Djurovic, Srdjan

AU - Melle, Ingrid

AU - Agartz, Ingrid

AU - Hall, Haakan

AU - Ullum, Henrik

AU - Timm, Sally

AU - Wang, August G

AU - Jönsson, Erik G

AU - Andreassen, Ole A

AU - Werge, Thomas

PY - 2008

Y1 - 2008

N2 - Schizophrenia is a highly heritable complex psychiatric disorder with an underlying pathophysiology that is still not well understood. Metaanalyses of schizophrenia linkage studies indicate numerous but rather large disease-associated genomic regions, whereas accumulating gene- and protein expression studies have indicated an equally large set of candidate genes that only partially overlap linkage genes. A thorough assessment, beyond the resolution of current GWA studies, of the disease risk conferred by the numerous schizophrenia candidate genes is a daunting and presently not feasible task. We undertook these challenges by using an established clinical paradigm, the estrogen hypothesis of schizophrenia, as the criterion to select candidates among the numerous genes experimentally implicated in schizophrenia. Bioinformatic tools were used to build and priorities the signaling networks implicated by the candidate genes resulting from the estrogen selection. We identified ten candidate genes using this approach that are all active in glucose metabolism and particularly in the glycolysis. Thus, we tested the hypothesis that variants of the glycolytic genes are associated with schizophrenia or at least with gender-associated aspects of the illness.

AB - Schizophrenia is a highly heritable complex psychiatric disorder with an underlying pathophysiology that is still not well understood. Metaanalyses of schizophrenia linkage studies indicate numerous but rather large disease-associated genomic regions, whereas accumulating gene- and protein expression studies have indicated an equally large set of candidate genes that only partially overlap linkage genes. A thorough assessment, beyond the resolution of current GWA studies, of the disease risk conferred by the numerous schizophrenia candidate genes is a daunting and presently not feasible task. We undertook these challenges by using an established clinical paradigm, the estrogen hypothesis of schizophrenia, as the criterion to select candidates among the numerous genes experimentally implicated in schizophrenia. Bioinformatic tools were used to build and priorities the signaling networks implicated by the candidate genes resulting from the estrogen selection. We identified ten candidate genes using this approach that are all active in glucose metabolism and particularly in the glycolysis. Thus, we tested the hypothesis that variants of the glycolytic genes are associated with schizophrenia or at least with gender-associated aspects of the illness.

U2 - 10.1186/1471-2350-9-39

DO - 10.1186/1471-2350-9-39

M3 - Journal article

SN - 1471-2350

VL - 9

SP - 39

JO - B M C Medical Genetics

JF - B M C Medical Genetics

ER -