HTR2A gene variation is involved in antidepressant treatment response.

Two serotonin 2A receptor (HTR2A) SNPs recently reported to be associated with antidepressant treatment response in STARD (rs7997012; rs1928040) were analyzed for association with treatment response in two independent Caucasian samples of patients with a Major Depressive Episode. In the combined sample (n=637) SNP rs7997012 was significantly associated with remission after five weeks providing first replicative support for the initial finding, with, however, an inverse allelic association as compared to the STARD sample.

Evaluation of nine candidate genes in patients with normal tension glaucoma: a case control study.

Background: Normal tension glaucoma is a major subtype of glaucoma, associated with intraocular pressures that are within the statistically normal range of the population. Monogenic forms following classical inheritance patterns are rare in this glaucoma subtype. Instead, multigenic inheritance is proposed for the majority of cases.

A genomewide association study points to multiple loci that predict antidepressant drug treatment outcome in depression.

Context: The efficacy of antidepressant drug treatment in depression is unsatisfactory; 1 in 3 patients does not fully recover even after several treatment trials. Genetic factors and clinical characteristics contribute to the failure of a favorable treatment outcome.

Objective: To identify genetic and clinical determinants of antidepressant drug treatment outcome in depression.

Variation in GRIN2B contributes to weak performance in verbal short-term memory in children with dyslexia.

A multi-marker haplotype within GRIN2B, a gene coding for a subunit of the ionotropic glutamate receptor, has recently been found to be associated with variation in human memory performance [de Quervain and Papassotiropoulos, 2006]. The gene locus is located within a region that has been linked to a phonological memory phenotype in a recent genome scan in families with dyslexia [Brkanac et al., 2008].

Investigation of 17 candidate genes for personality traits confirms effects of the HTR2A gene on novelty seeking.

Genes involved in serotonergic and dopaminergic neurotransmission have been hypothesized to affect different aspects of personality, but findings from genetic association studies did not provide conclusive results so far. In previous studies, however, only one or a few polymorphisms within single genes were investigated neglecting the possibility that the genetic associations might be more complex comprising several genes or gene regions. To overcome this limitation, we performed an extended genetic association study analyzing 17 serotonergic (SLC6A4, HTR1A, HTR1B, HTR2A, HTR2C, HTR3A, HTR6, MAOA, TPH1, TPH2) and dopaminergic genes (SLC6A3, DRD2, DRD3, DRD4, COMT, MAOA, TH, DBH), which have been previously reported to be implicated with personality traits.

Sequence variants on chromosome 9p21.3 confer risk for atherosclerotic stroke.

Objective: Recent studies have identified a major locus for risk for coronary artery disease and myocardial infarction on chromosome 9p21.3. Stroke, in particular, ischemic stroke caused by atherosclerotic disease, shares common mechanisms with myocardial infarction.

Epistasis between Toll-like receptor-9 polymorphisms and variants in NOD2 and IL23R modulates susceptibility to Crohn's disease.

Objectives: Recent data suggest functional interactions between NOD2 and other receptors of the innate immune system modulating inflammatory responses. Here we analyzed the role of Toll-like receptor 9 (TLR-9) gene variants with respect to susceptibility to inflammatory bowel disease (IBD) and tested for genetic interactions with NOD2 and other susceptibility genes for Crohn's disease (CD).

Methods: The single-nucleotide polymorphisms (SNPs) -1237T/C (rs5743836) and 2848A/G (rs352140=p.

Novel genetic risk markers for ulcerative colitis in the IL2/IL21 region are in epistasis with IL23R and suggest a common genetic background for ulcerative colitis and celiac disease.

Objectives: Recently, a genome-wide association study showed that single-nucleotide polymorphisms (SNPs) in the chromosome 4q27 region containing IL2 and IL21 are associated with celiac disease. Given the increased prevalence of inflammatory bowel disease (IBD) among celiac disease patients, we investigated the possible involvement of these SNPs in IBD.

Methods: Five SNPs strongly associated with celiac disease within the KIAA1109/TENR/IL2/IL21 linkage disequilibrium block on chromosome 4q27 and one coding SNP within the IL21 gene were analyzed in a large German IBD cohort.

Gene expression patterns associated with posttraumatic stress disorder following exposure to the World Trade Center attacks.

Background: Although genetic risk factors for posttraumatic stress disorder (PTSD) in similarly traumatized cohorts can be confounded with risk for type of exposure, the primary risk for exposure to the 9/11 attack on New York City was proximity, allowing study of PTSD risk in a sample that is not confounded by exposure-related risk.

Methods: Thirty-five Caucasians (15 with PTSD, stratified for exposure, age, and gender) were selected from a population-representative sample of persons exposed to the attack from which longitudinal data had been collected in four previous waves. Whole blood gene expression and cortisol levels were obtained.

A novel locus for arterial hypertension on chromosome 1p36 maps to a metabolic syndrome trait cluster in the Sorbs, a Slavic population isolate in Germany.

Objective: Genome-wide linkage studies and genome-wide association studies have not as yet identified major genes contributing to primary hypertension in the general population. This state-of-affairs suggests considerable heterogeneity with small contributing effects for primary hypertension, or other complex genetic traits, in outbred populations. Isolated populations, as recent data from Iceland and French Canada suggest, could offer a solution to this problem.

Lysyl oxidase-like 1 gene polymorphisms in German patients with normal tension glaucoma, pigmentary glaucoma and exfoliation glaucoma.

Purpose: To evaluate the association between lysyl-oxidase-like 1 (LOXL1) gene polymorphisms and exfoliation glaucoma, pigmentary glaucoma and normal tension glaucoma in a case-control cohort of German patients.

Methods: Six single nucleotide polymorphisms in a 22 kb genomic region encompassing the LOXL1 gene plus an additional "outlier" single nucleotide polymorphism located approximately 1.1 Mb upstream of LOXL1 were genotyped in 128 exfoliation glaucoma patients, 88 pigmentary glaucoma patients, 273 normal tension glaucoma patients, and 280 healthy control subjects either with TaqMan allelic discrimination assays or by direct sequencing, and a genetic association study was performed.

A hypomorphic vasopressin allele prevents anxiety-related behavior.

Background: To investigate neurobiological correlates of trait anxiety, CD1 mice were selectively bred for extremes in anxiety-related behavior, with high (HAB) and low (LAB) anxiety-related behavior mice additionally differing in behavioral tests reflecting depression-like behavior.

Methodology/ Principal Findings: In this study, microarray analysis, in situ hybridization, quantitative real-time PCR and immunohistochemistry revealed decreased expression of the vasopressin gene (Avp) in the hypothalamic paraventricular (PVN) and supraoptic (SON) nuclei of adult LAB mice compared to HAB, NAB (normal anxiety-related behavior) and HABxLAB F1 intercross controls, without detecting differences in receptor expression or density. By sequencing the regions 2.

Common variants at ten loci modulate the QT interval duration in the QTSCD Study.

The QT interval, a measure of cardiac repolarization, predisposes to ventricular arrhythmias and sudden cardiac death (SCD) when prolonged or shortened. A common variant in NOS1AP is known to influence repolarization. We analyze genome-wide data from five population-based cohorts (ARIC, KORA, SardiNIA, GenNOVA and HNR) with a total of 15,842 individuals of European ancestry, to confirm the NOS1AP association and identify nine additional loci at P < 5 x 10(-8).

Replication of restless legs syndrome loci in three European populations.

Background: Restless legs syndrome (RLS) is associated with common variants in three intronic and intergenic regions in MEIS1, BTBD9, and MAP2K5/LBXCOR1 on chromosomes 2p, 6p and 15q.

Methods: Our study investigated these variants in 649 RLS patients and 1230 controls from the Czech Republic (290 cases and 450 controls), Austria (269 cases and 611 controls) and Finland (90 cases and 169 controls). Ten single nucleotide polymorphisms (SNPs) within the three genomic regions were selected according to the results of previous genome-wide scans.

rs224136 on chromosome 10q21.1 and variants in PHOX2B, NCF4, and FAM92B are not major genetic risk factors for susceptibility to Crohn's disease in the German population.

Objectives: Recently, a North American genome-wide association study identified three novel gene variants in PHOX2B, NCF4, and FAM92B as well as one single nucleotide polymorphisms (SNP; rs224136) in the intergenic region on chromosome 10q21.1 as being associated with Crohn's disease (CD). However, their influence on European CD patients as well as ulcerative colitis (UC) is unknown.

Further evidence for DYX1C1 as a susceptibility factor for dyslexia.

Objective: Dyslexia-susceptibility-1-candidate-1 (DYX1C1) was the first gene associated with dyslexia. Since the original report of 2003, eight replication attempts have been published reporting discordant results. As the dyslexia community still considers the role of DYX1C1 unsettled, we explored the contribution of this gene in a sample of 366 trios of German descent.

Polymorphisms in the GAD2 gene-region are associated with susceptibility for unipolar depression and with a risk factor for anxiety disorders.

Glutamate decarboxylase (GAD) is the rate limiting enzyme for conversion of glutamic acid to gamma-aminobutyric acid (GABA). The GAD 65 kDa isoform is encoded by the gene GAD2 and is mainly expressed in synaptic terminals. It serves as an apoenzyme, which shows enhanced availability in situations of stress, responding to short-term demands for GABA.

Genetic variation in the lymphotoxin-alpha pathway and the risk of ischemic stroke in European populations.

Background And Purpose: Several genes involved in the lymphotoxin-alpha cascade (LTA, LGALS2, and PSMA6) have been linked with the risk of myocardial infarction. Here, we present a comprehensive analysis of these genes in patients with ischemic stroke (IS).

Methods: Twenty-three single nucleotide polymorphisms (SNPs) from LTA, LGALS2, and PSMA6 were genotyped in 601 German IS patients and 736 matched controls.

Proteomic-based genotyping in a mouse model of trait anxiety exposes disease-relevant pathways.

In our biomarker identification efforts, we have reported earlier on a protein that differs in its electrophoretic mobility between mouse lines bred either for high or low trait anxiety. The altered electrophoretic behavior of enolase phosphatase (EP) is now identified to be caused by two single-nucleotide polymorphisms. In both cases, the genetic polymorphism introduces an amino acid change in the protein's sequence resulting in differential mobility on SDS gels.

Variations in tryptophan hydroxylase 2 linked to decreased serotonergic activity are associated with elevated risk for metabolic syndrome in depression.

Major depression and the metabolic syndrome (MetS) are interacting clinical conditions influenced by genetic susceptibility. For both disorders, impaired serotonergic neurotransmission in specific brain areas has been suggested. This led us to investigate whether variants in the gene coding for tryptophan hydroxylase 2 (TPH2), the brain-specific and rate-limiting enzyme for serotonin biosynthesis, might be predictive for an increased liability for the development of MetS in depressed patients.

Genome-wide association study of recurrent major depressive disorder in two European case-control cohorts.

Major depressive disorder (MDD) is a highly prevalent disorder with substantial heritability. Heritability has been shown to be substantial and higher in the variant of MDD characterized by recurrent episodes of depression. Genetic studies have thus far failed to identify clear and consistent evidence of genetic risk factors for MDD.

Investigation of the DCDC2 intron 2 deletion/compound short tandem repeat polymorphism in a large German dyslexia sample.

Dyslexia is a complex disorder manifested by difficulties in learning to read and spell despite conventional instruction, adequate intelligence and sociocultural opportunity. It is among the most common neurodevelopmental disorders with a prevalence of 5-12%. The dyslexia susceptibility locus 2 on chromosome 6p21-p22 is one of the best-replicated linkage regions in dyslexia.

Mouse to human comparative genetics reveals a novel immunoglobulin E-controlling locus on Hsa8q12.

Atopy is a predisposition to hyperproduction of immunoglobulin E (IgE) against common environmental allergens. It is often associated with development of allergic diseases such as asthma, rhinitis, and dermatitis. Production of IgE is influenced by genetic and environmental factors.

Investigation of interaction between DCDC2 and KIAA0319 in a large German dyslexia sample.

The dyslexia susceptibility locus DYX2 (chr. 6p21-p22) harbours two candidate genes, DCDC2 and KIAA0319. In 2006, Harold et al.