Association of Common Polymorphisms in the Nicotinic Acetylcholine Receptor Alpha4 Subunit Gene with an Electrophysiological Endophenotype in a Large Population-Based Sample.

Variation in genes coding for nicotinic acetylcholine receptor (nAChR) subunits affect cognitive processes and may contribute to the genetic architecture of neuropsychiatric disorders. Single nucleotide polymorphisms (SNPs) in the CHRNA4 gene that codes for the alpha4 subunit of alpha4/beta2-containing receptors have previously been implicated in aspects of (mostly visual) attention and smoking-related behavioral measures. Here we investigated the effects of six synonymous but functional CHRNA4 exon 5 SNPs on the N100 event-related potential (ERP), an electrophysiological endophenotype elicited by a standard auditory oddball.

Genetic Geostatistical Framework for Spatial Analysis of Fine-Scale Genetic Heterogeneity in Modern Populations: Results from the KORA Study.

Aiming to investigate fine-scale patterns of genetic heterogeneity in modern humans from a geographic perspective, a genetic geostatistical approach framed within a geographic information system is presented. A sample collected for prospective studies in a small area of southern Germany was analyzed. None indication of genetic heterogeneity was detected in previous analysis.

Analysis of quantitative trait loci in mice suggests a role of Enoph1 in stress reactivity.

Significant progress in elucidating the genetic etiology of anxiety and depression has been made during the last decade through a combination of human and animal studies. In this study, we aimed to discover genetic loci linked with anxiety as well as depression in order to reveal new candidate genes. Therefore, we initially tested the behavioral sensitivity of 543 F2 animals derived from an intercross of C57BL/6J and C3H/HeJ mice in paradigms for anxiety and depression.

Familial aggregation of pure tone hearing thresholds in an aging European population.

Objective: To investigate the familial correlations and intraclass correlation of age-related hearing impairment (ARHI) in specific frequencies. In addition, heritability estimates were calculated.

Study Design: Multicenter survey in 8 European centers.

Functional polymorphism in the neuropeptide Y gene promoter (rs16147) is associated with serum leptin levels and waist-hip ratio in women.

Objective: The neuropeptide-Y (NP-Y) gene is a strong candidate gene in the pathophysiology of obesity-linked behavior, and several single-nucleotide polymorphisms of NP-Y have already been linked to body weight and appetite. However, the results from current studies remain inconclusive. The aim of the present study was to test whether a certain functional genetic variant (SNP rs16147) in the NP-Y promoter gene is associated with serum leptin levels and body fat distribution.

Lack of association of a functional catechol-O-methyltransferase gene polymorphism with risk of tobacco smoking: results from a multicenter case-control study.

Background: The catechol-O-methyltransferase (COMT) modulates dopaminergic neurotransmission in the prefrontal cortex as well as in the mesolimbic reward system. Since the reward system mediates addictive behavior, the COMT gene is a strong candidate gene regarding the pathophysiology of tobacco dependence and smoking behavior. Because of rather conflicting results in previous studies, the purpose of the present study was to test for association between a functional genetic variant in the COMT gene (single nucleotide polymorphism [SNP] rs4680) and tobacco smoking behavior.

Impaired sleep quality and sleep duration in smokers-results from the German Multicenter Study on Nicotine Dependence.

Cigarette smoking is a severe health burden being related to a number of chronic diseases. Frequently, smokers report about sleep problems. Sleep disturbance, in turn, has been demonstrated to be involved in the pathophysiology of several disorders related to smoking and may be relevant for the pathophysiology of nicotine dependence.

Genetic variation in the neuropeptide Y gene promoter is associated with increased risk of tobacco smoking.

Background: Neuropeptide Y (NPY) is a strong candidate gene regarding the pathophysiology of tobacco dependence. It has been associated with various addictive and psychiatric disorders, and closely interacts with the brain reward system. The aim of the present study was to test for association between a functional genetic variant in the NP-Y promoter gene (SNP rs16147) and tobacco smoking.

Schizophrenia risk polymorphisms in the TCF4 gene interact with smoking in the modulation of auditory sensory gating.

Several polymorphisms of the transcription factor 4 (TCF4) have been shown to increase the risk for schizophrenia, particularly TCF4 rs9960767. This polymorphism is associated with impaired sensorimotor gating measured by prepulse inhibition--an established endophenotype of schizophrenia. We therefore investigated whether TCF4 polymorphisms also affect another proposed endophenotype of schizophrenia, namely sensory gating assessed by P50 suppression of the auditory evoked potential.

Neurocognitive impairments in non-deprived smokers--results from a population-based multi-center study on smoking-related behavior.

The aim of the present study was to examine neurocognitive function associated with chronic nicotine use. A total of 2163 healthy participants (1002 smokers, 1161 never-smoking controls) participated in a population-based case-control design. The main outcome measures were six cognitive domain factors derived from a neuropsychological test battery.

The German multi-centre study on smoking-related behavior-description of a population-based case-control study.

Tobacco smoking is a major risk factor for most of the diseases leading in mortality. Nicotine dependence (ND), which sustains regular smoking, is now acknowledged to be under substantial genetic control with some environmental contribution. At present, however, genetic studies on ND are mostly conducted in populations that have been poorly characterized with regard to ND-related phenotypes for the simple reason that the respective populations were not primarily collected to study ND.

P50 sensory gating and smoking in the general population.

P50 gating is a major functional biomarker in research on schizophrenia and other psychiatric conditions with high smoking prevalence. It is used as endophenotype for studying nicotinic systems genetics and as surrogate endpoint measure for drug development of nicotinic agonists. Surprisingly, little is known about P50 gating in the general population and the relationship to smoking-related characteristics.

Caspase recruitment domain 15 gene haplotypes in sarcoidosis.

Sarcoidosis is a systematic granulomatous disorder. Genetic susceptibility could play a central role in the disease development and progression. In this study, we investigated whether caspase recruitment domain 15 (CARD15) gene haplotypes are associated with the onset or the clinical course of sarcoidosis.

Methylation at global LINE-1 repeats in human blood are affected by gender but not by age or natural hormone cycles.

Previously, we reported on inter-individual and gender specific variations of LINE-1 methylation in healthy individuals. In this study, we investigated whether this variability could be influenced by age or sex hormones in humans. To this end, we studied LINE-1 methylation in vivo in blood-derived DNA from individuals aged 18 to 64 years and from young healthy females at various hormone levels during the menstrual cycle.

Geostatistical inference of main Y-STR-haplotype groups in Europe.

We examined the multifarious genetic heterogeneity of Europe and neighboring regions from a geographical perspective. We created composite maps outlining the estimated geographical distribution of major groups of genetically similar individuals on the basis of forensic Y-chromosomal markers. We analyzed Y-chromosomal haplotypes composed of 7 highly polymorphic STR loci, genotyped for 33,010 samples, collected at 249 sites in Europe, Western Asia and North Africa, deposited in the YHRD database (www.

Spatial assessment of Argentinean genetic admixture with geographical information systems.

In recent years there has been much attention to Argentinean population stratification. We were interested in assessing population stratification from a geographical perspective and summarizing it in form of maps. We mapped the genetic admixture of the extant male population in central and northern Argentina on the basis of forensic Y-chromosomal haplotypes.

The P300 event-related potential and smoking--a population-based case-control study.

A better understanding of the factors underlying habitual tobacco smoking may further new strategies to go about this major health problem. The P300 event-related potential (ERP) has emerged as a valuable (endo)phenotype in neuropsychiatric research. Previous studies suggested the P300 ERP to be reduced in smokers.

IRF6 gene variants in Central European patients with non-syndromic cleft lip with or without cleft palate.

Variants in the interferon regulatory factor 6 (IRF6) gene have repeatedly been associated with non-syndromic cleft lip with or without cleft palate (NSCL/P). A recent study has suggested that the functionally relevant variant rs642961 is the underlying cause of the observed associations. We genotyped rs642961 in our Central European case-control sample of 460 NSCL/P patients and 952 controls.

Genome-wide linkage scan of nonsyndromic orofacial clefting in 91 families of central European origin.

Orofacial clefts are among the most common of all congenital disorders. Nonsyndromic cases of cleft lip with or without cleft palate (NSCL/P) and cleft palate only (NSCPO) are considered to have a multifactorial etiology which involves both genetic and environmental factors. We present the results of a genome-wide linkage scan in 91 families of central European descent with nonsyndromic orofacial clefts (NSC).

VEGF gene haplotypes are associated with sarcoidosis.

Background: The cause of sarcoidosis is unclear. Evidence suggests that there is a genetic susceptibility toward the disease. In this study, we examined whether haplotypes of vascular endothelial growth factor (VEGF) and its receptors VEGFR-1 and VEGFR-2 are associated with the onset or the course of sarcoidosis.

Further evidence for the involvement of MYH9 in the etiology of non-syndromic cleft lip with or without cleft palate.

Non-syndromic cleft lip with or without cleft palate (NSCL/P) is one of the most common birth defects and has a multifactorial etiology that includes both genetic and environmental components. MYH9, the gene coding for the heavy chain of non-muscle myosin II, has been considered as a good candidate gene in NSCL/P on the basis of its expression profile during craniofacial morphogenesis. Reports in an Italian sample, as well as in an ethnically mixed North American sample, of a positive association between single-nucleotide polymorphisms in the MYH9 gene and NSCL/P have provided further support for the role of MYH9 in the development of NSCL/P.

A systematic search for DNA methyltransferase polymorphisms reveals a rare DNMT3L variant associated with subtelomeric hypomethylation.

Causes underlying inter-individual variations in DNA methylation profiles among normal healthy populations are not thoroughly understood. To investigate the contribution of genetic variation in DNA methyltransferase (DNMT) genes to such epigenetic variation, we performed a systematic search for polymorphisms in all known human DNMT genes [DNMT1, DNMT3A, DNMT3B, DNMT3L and DNMT2 (TRDMT1)] in 192 healthy males and females. One hundred and eleven different polymorphisms were detected.

Occupational noise, smoking, and a high body mass index are risk factors for age-related hearing impairment and moderate alcohol consumption is protective: a European population-based multicenter study.

A multicenter study was set up to elucidate the environmental and medical risk factors contributing to age-related hearing impairment (ARHI). Nine subsamples, collected by nine audiological centers across Europe, added up to a total of 4,083 subjects between 53 and 67 years. Audiometric data (pure-tone average [PTA]) were collected and the participants filled out a questionnaire on environmental risk factors and medical history.

Familial aggregation of tinnitus: a European multicentre study.

Introduction And Aim: Tinnitus is a common condition affecting approximately 20% of the older population. There is increasing evidence that changes in the central auditory system following cochlear malfunctioning are responsible for tinnitus. To date, few investigators have studied the influence of genetic factors on tinnitus.

Increased frequency of the CTLA-4 49 A/G polymorphism in patients with acquired haemophilia A compared to healthy controls.

Acquired haemophilia (AH) is an autoimmune disorder characterized by autoantibodies against endogenous factor VIII (FVIII). Half of the patients present with an underlying disease known to cause the FVIII autoantibodies whereas in the other half the disease is of idiopathic nature. Recently, it has been shown that variants of the polymorphic cytotoxic T lymphocyte antigen-4 (CTLA-4) gene are associated with autoimmune diseases and also represent a risk factor for inhibitor formation in inherited haemophilia A.