bluuebunny/crossref_metadata_2025_split huggingface dataset:
Initial genome‐wide scan for linkage with schizophrenia in the Japanese schizophrenia sib‐pair linkage group (JSSLG) families
Authors: Arinami T. ,   Japanese Schizophrenia Sib‐Pair Linkage Group (JSSLG)
Published: June 2003

AbstractTo determine if there are common genes that contribute to the susceptibility for schizophrenia, first‐stage genome‐wide scan was carried out by genotyping 417 short‐tandem repeat (STR) markers in 338 individuals from 130 families with 148 affected sib‐pairs identified at 16 sites nationwide in Japan. Data was from the Japanese Schizophrenia Sib‐pair Linkage Group (JSSLG), which is a multi‐site collaborative study group established to create a national resource for genetic studies of schizophrenia in Japan. All subjects were Japanese, and the probands and their siblings had schizophrenia. Multipoint non‐parametric linkage analysis and exclusion mapping were performed with GENEHUNTER software. Simulation studies suggested that in the absence of linkage we could expect one multipoint maximum LOD score (MLS) of 1.9 per genome scan. An MLS of 3.7 would be expected only once in every 20 genome scans and thus corresponds to a genome‐wide significance of 0.05. No loci in the initial screen fulfilled the criteria for significant or suggestive evidence for linkage. Ten chromosomes (1, 2, 3, 4, 5, 8, 9, 14, 17, and 20) had at least one region with a nominal P value < 0.05. Susceptibility genes with λs of 3 and 2 were excluded from 98 and 70% of the genome, respectively. Our results suggest that common genes that contribute significantly to susceptibility for schizophrenia are unlikely to exist in the Japanese population. © 2003 Wiley‐Liss, Inc.
Relationship between catechol‐O‐methyltransferase polymorphism and treatment‐resistant schizophrenia
Authors: Inada Toshiya , Nakamura Ataru , Iijima Yoshimi 
Published: June 2003

AbstractCatechol‐O‐methyltransferase (COMT) plays a crucial role in the regulation of central dopaminergic systems. We examined the allelic association of a functional polymorphism of the COMT gene with the clinical manifestations and the response to antipsychotics of 100 schizophrenic patients and 201 healthy controls from the general Japanese population. No statistically significant difference was observed in the allele and genotype frequencies between the schizophrenic patients and the healthy controls. The daily neuroleptic dosage that patients received during their maintenance therapy was significantly higher in patients with the L/L genotype than in the other patients (P < 0.05). The present results suggest that the presence of the COMT genotype does not help in evaluating the susceptibility to the development of schizophrenia, but that it may help in the estimation of treatment‐resistant features of schizophrenia. © 2003 Wiley‐Liss, Inc.
Apolipoprotein E Pittsburgh variant is not associated with the risk of late‐onset Alzheimer's disease in a Spanish population
Authors: Baron M. , Jimenez‐Escrig A. , Orensanz L. , Simon J. , Perez‐Tur J. 
Published: June 2003

AbstractThe objective of this study was to assess whether the APOEPittsburghvariant (APOE*4P) is associated to Alzheimer's disease (AD) in a population from Madrid (Spain). APOE*4P variant is caused by an exonic mutation which results in the substitution of proline‐28 for leucine‐28, only present in APOE*4 alleles. A study in a US population associated this APOE variant with an increased risk for AD, about five times higher than the risk attributed to APOE*4 carriers overall. One hundred and seventeen cases of late‐onset AD and 121 matched control subjects from Madrid (Spain) were included. We studied the APOE polymorphism and the APOE*4P occurrence, by PCR and restriction analysis, and plasma lipids levels using standard protocols. As expected, APOE*4 was significantly overrepresented in AD cases. The APOE*4P mutation was observed in heterozygous state in four subjects, two AD (1.71%) and two controls (1.65%). APOE*4P did not confer higher risk for AD, globally (odds ratio 0.14; 95% confidence interval (CI) 0.02–1.12) or respect to APOE*4 carriers (odds ratio 0.14; 95% CI 0.02–1.24). There were no differences in plasma lipids levels among genotype groups. The mutation frequency in controls was higher in our sample than in the US one (1.65 and 0.18%, respectively; Fisher testP = 0.049). Our results suggest that this variant is not so uncommon in our population and is not directly related to AD, contrary to what has been proposed for other populations. © 2003 Wiley‐Liss, Inc.
Etiology of the comorbidity between RD and ADHD: Exploration of the non‐random mating hypothesis
Authors: Friedman Melanie C. , Chhabildas Nomita , Budhiraja Nisha , Willcutt Erik G. , Pennington Bruce F. 
Published: June 2003

AbstractThe present research sought to test the validity of the non‐random mating hypothesis in a community sample in order to determine whether it contributes significantly to the comorbidity between attention‐deficit/hyperactivity disorder (ADHD) and reading disability (RD) and to test whether the two disorders segregate independently. Data were gathered from 394 twin participants of the Colorado Learning Disabilities Research Center (CLDRC) and their biological parents. Parents were asked to complete retrospective questionnaires regarding their own ADHD and RD symptomatology as children, as well as rate their children on DSM‐IV ADHD symptomatology before age 12. Twin RD was assessed by a composite score consisting of several reading measures. Chi‐square and correlational analyses assessed the presence of non‐random mating, as well as whether the two disorders were transmitted independently. Non‐random mating between those with ADHD and those with RD did not significantly contribute to the comorbidity of the two disorders. Furthermore, there was some evidence that these two disorders did not segregate independently in this sample. These results are consistent with recent evidence that ADHD and RD are often comorbid because of significant genetic overlap. There was little evidence to support that non‐random mating also contributes to this comorbidity in the present sample. © 2003 Wiley‐Liss, Inc.
Family‐based association study of markers on chromosome 22 in schizophrenia using African‐American, European‐American, and Chinese families
Authors: Takahashi Sakae , Cui Yu‐hu , Kojima Takuya , Han Yong‐hua , Zhou Ru‐lum , Kamioka Masashi , Yu Shun‐ying , Matsuura Masato , Matsushima Eisuyke , Wilcox Marsha , Arinami Tadao , Shen Yu‐cun , Faraone Stephen V. , Tsuang Ming T. 
Published: June 2003

AbstractSeveral studies suggest that loci at chromosome 22q11.2‐q13 might be linked to susceptibility to schizophrenia. Here we performed family‐based association studies on chromosome 22q using 12 DNA microsatellite markers in African‐American, European‐American, and Chinese pedigrees. The marker D22S683 showed significant linkage and association with schizophrenia in not only the European‐American sample but also in a combined sample (European‐American and Chinese samples). Notably, D22S683 is located nearby and between D22S278 and D22S283, which have shown linkage and association to schizophrenia in prior reports. However, we found no significant association for the African‐American sample. In conclusion, our data provide further support for the idea that the region around D22S683 contains a susceptibility gene for schizophrenia. © 2003 Wiley‐Liss, Inc.
Mutation screening of the Homer gene family and association analysis in schizophrenia
Authors: Norton N. , Williams H.J. , Williams N.M. , Spurlock G. , Zammit S. , Jones G. , Jones S. , Owen R. , O'Donovan M.C. , Owen M.J. 
Published: June 2003

AbstractHomer proteins are a group of proteins that regulate group 1 metabotropic glutamate receptor function. As altered glutamate function has been implicated in many neuro psychiatric disorders, particularly schizophrenia, we have screened all three known Homer genes for sequence variation for use under the candidate gene association paradigm. We found seven SNPs, including three in exons. Of these, none was non‐synonymous. Allele frequencies of all the detected SNPs were estimated in DNA pools of 368 schizophrenics and 368 controls. Only one (Homer 1 IVS4 + 18A > G) was associated with schizophrenia in this sample, a finding confirmed by individual genotyping (P = 0.01). However, in our extended sample of 680 cases and 671 controls, the evidence for association diminished (P = 0.05). Our results suggest it is unlikely that sequence variants in the Homer genes contribute to the aetiology of schizophrenia, but the variants we identified are plausible candidates for other neuropsychiatric phenotypes. © 2003 Wiley‐Liss, Inc.
NURR1 promoter polymorphisms: Parkinson's disease, schizophrenia, and personality traits
Authors: Carmine Andrea , Buervenich Silvia , Galter Dagmar , Jönsson Erik G. , Sedvall Göran C. , Farde Lars , Gustavsson J. Petter , Bergman Hans , Chowdari Kodavali V. , Nimgaonkar Vishwajit L. , Anvret Maria , Sydow Olof , Olson Lars 
Published: June 2003

AbstractWe have previously identified mutations in exon three in NURR1 (NR4A2) in two patients with schizophrenia (SZ) and one patient with bipolar disease with psychotic symptoms. In the present study we analyzed the promoter region of NURR1 and identified five polymorphic sites: three were found to be in strong linkage disequilibrium with a previously identified polymorphic site in the sixth intron. One polymorphism of this haplotype and the two other independent polymorphisms were investigated for their possible association with SZ and Parkinson's disease (PD) by comparing their frequencies in a Swedish material consisting of 134 subjects with SZ and 207 matched controls and 108 subjects with PD and 125 matched controls. Exon 1 was also investigated in our Parkinson and control material but no variances were found. The distributions of the two most informative polymorphisms in the promoter were investigated in an American material as well consisting of 141 subjects with SZ and 139 matched controls. Furthermore, the identified markers were screened for association with putative endophenotypes of SZ in the Swedish material. The distribution of sequence variants among the Swedish controls matched for SZ was investigated with regard to personality. No significant genotype or allelic association of the three sequence variants with SZ or PD was found. Several comparisons regarding endophenotypes or personality indicated association at the 5% confidence level, although correction for multiple testing rendered none of these findings significant. We conclude that the identified polymorphic sites in the human NURR1 are unlikely to be involved in conferring susceptibility for SZ or PD in our patient material. © 2003 Wiley‐Liss, Inc.
Haplotypes at the OPRM1 locus are associated with susceptibility to substance dependence in European‐Americans
Authors: Luo Xingguang , Kranzler Henry R. , Zhao Hongyu , Gelernter Joel 
Published: June 2003

AbstractOur objective was to investigate the relationship between the gene encoding the μ‐opioid receptor (OPRM1) and susceptibility to substance dependence in European‐American (EA) and African‐American (AA) subjects. Eight single nucleotide polymorphisms (SNPs) at the OPRM1 locus, i.e., −2044C/A, −1793T/A, −1699insT, −1469T/C, −1320A/G, −111C/T, +17C/T (Ala6Val), and +118A/G (Asn40Asp) were genotyped in 676 subjects: 318 EA subjects and 124 AA subjects with substance dependence, and 179 EA normal controls, and 55 AA normal controls. Affection status was defined by each unique combination of alcohol, cocaine, and opioid dependence and analysis of association examined in relation to the possible combinations. We used a newly implemented permutation method to evaluate statistical significance. In EAs, a significant difference in haplotype frequency distributions was found between controls and “alcohol + opioid” dependent patients (P = 0.0036). This finding is also supported by logistic regression analysis and a simulation method. The frequencies of allele −2044A and haplotypes including −2044A are higher in these patients than in controls. In AAs, no allele, haplotype, or genotype frequencies were significantly different between cases and controls. There were highly significant differences in the allele, haplotype, and genotype frequencies between EA and AA controls. Four of the variants [−1793T/A, −1699insT, −1320A/G, and −111C/T] are in virtually complete linkage disequilibrium (LD) to compose a sequence pattern, which does not associate with any of the seven categories of substance dependence. In EAs, allele −2044A and haplotypes that include −2044A are the susceptibility allele and haplotypes for substance dependence. These findings suggest that OPRM1 may play a role in the pathophysiology of substance dependence and this role is population‐ and diagnosis‐specific. © 2003 Wiley‐Liss, Inc.
Monoamine oxidase B polymorphism, cigarette smoking and risk of Parkinson's disease: A study in an Asian population
Authors: Tan E.K. , Chai A. , Lum S.Y. , Shen H. , Tan C. , Teoh M.L. , Yih Y. , Wong M.C. , Zhao Y. 
Published: June 2003

AbstractCigarette smoking is associated with reduced monoamine oxidase B (MAO B) activity. Polymorphisms of the MAO B gene may modify the relationship between smoking and Parkinson's Disease (PD). We examined the association of MAO B intron 13 G/A polymorphism and risk of PD, and the modulation of the polymorphism on smoking and PD in an Asian study population in Singapore. Two hundred and thirty PD patients (mean age 66.0 ± 9.4 years, 63% men) and 241 age, gender, and race matched controls (mean age 64 ± 9.2 years, 58.9% males) were studied. The frequency of G and A alleles in PD and controls was; 66/315 (21.0%) vs. 73/340 (21.5%) and 249/315 (79.0%) vs. 267/340 (78.5%). For women, the genotype frequency in PD and controls was; GG: 7/85 (8.2%) vs. 8/99 (8.1%); GA: 25/85 (29.4%) vs. 27/99 (27.3%); AA: 53/85 (62.4%) vs. 64/99 (64.6%). For men, allele frequency in PD and controls was; A: 118/145 (81.4%) vs. 112/142 (78.9%) and G: 27/145 (18.6%) vs. 30/142 (21.1%). The allele and genotype frequencies were not significantly different between young and late onset PD. The frequency of “ever” smokers in PD and controls was 31/230 (13.5%) vs. 52/241 (21.6%), P = 0.02. A stepwise logistic regression analysis did not reveal any interaction of smoking and the G allele and risk of PD. The MAO B G/A genotype frequency in our Asian population was quite different from Caucasians suggesting that ethnicity specific effects need to be considered in evaluating gene‐environmental interaction. © 2003 Wiley‐Liss, Inc.
Association between Val108/158met polymorphism of theCOMTgene and schizophrenia
Authors: Wonodi Ikwunga , Stine O. Colin , Mitchell Braxton D. , Buchanan Robert W. , Thaker Gunvant K. 
Published: June 2003

AbstractSchizophrenia is a complex disorder with a multifactorial polygenic inheritance with several genes conferring susceptibility at many genetic locations, each with a small effect. An attractive candidate gene for schizophrenia is the catechol‐O‐methyltransferase (COMT) gene, which is a modulator of dorsolateral prefrontal cortical function. A missense G to A mutation in this gene that results in a substitution of Methionine (Met) for Valine (Val) at codon 108/158 (Val108/158Met) has recently been identified in association to schizophrenia. We compared allele frequencies of the variant Val allele between 96 schizophrenia cases and 80 normal controls. We selected controls from a similar pool to cases in ethnicity and gender. The frequency of the Val allele was significantly higher in schizophrenia cases compared to controls (0.620 vs. 0.506;P = 0.043). Calculation of the population attributable risk suggests that the Val allele accounts for as much as 23% of schizophrenia in this population (range: 3–38%). These results provide support for a role of this variant in the etiopathophysiology of schizophrenia. © 2003 Wiley‐Liss, Inc.
Genome wide scan using homozygosity mapping and linkage analyses of a single pedigree with affective disorder suggests oligogenic inheritance
Authors: Ewald Henrik , Kruse Torben A. , Mors Ole 
Published: June 2003

AbstractThe present study reports results from a genome scan on a family with bipolar affective disorder in which the parents are first cousins and four of the offsprings and one grandchild have affective disorder. The study searched for risk loci for affective disorder by searching for homozygous segments or more complex inherited loci using parametric and non‐parametric multipoint linkage analysis. In addition dominant, multipoint, affecteds‐only linkage analyses were performed as a supplement to previous analyses. On chromosomes 2q31.3, 10, 12q24, and 21q22.3 evidence for a risk locus was obtained by parametric and/or non‐parametric linkage analyses and by haplotype sharing. As other studies have found significant or suggestive linkage to bipolar disorder in these chromosome regions this suggests that an oligogenic mode of inheritance is possible in this family involving at least some of the loci. Finally, the work discusses whether homozygosity mapping using parametric and non‐parametric linkage analyses may be of value for complex diseases including rare subphenotypes of such disorders. © 2003 Wiley‐Liss, Inc.
Association of mitochondrial complex I subunit gene NDUFV2 at 18p11 with bipolar disorder
Authors: Washizuka Shinsuke , Kakiuchi Chihiro , Mori Kanako , Kunugi Hiroshi , Tajima Osamu , Akiyama Tsuyoshi , Nanko Shinichiro , Kato Tadafumi 
Published: June 2003

AbstractLinkage of bipolar disorder with 18p11 has been replicated by several investigators. A nuclear‐encoded mitochondrial complex I subunit gene, NDUFV2, is one of the candidate genes in this locus, since the possible pathophysiological significance of mitochondrial dysfunction in bipolar disorder has been suggested. The objective of our study was to clarify the association between the NDUFV2 gene and bipolar disorder. We performed the real‐time quantitative reverse transcription polymerase chain reaction (RT‐PCR) for NDUFV2 mRNA expression in lymphoblastoid cell lines derived from patients with bipolar disorder and healthy controls. We also screened novel polymorphisms using denaturing high performance liquid chromatography (D‐HPLC) and PCR‐direct sequencing method. Detected five single nucleotide polymorphisms (SNPs) were genotyped. A decrease of the expression level of NDUFV2 gene was found in patients with bipolar I disorder compared with controls (P = 0.006). We also found that the haplotype frequencies of the four polymorphisms in the upstream region of NDUFV2 were significantly different between bipolar disorders and controls (P = 0.0001). Our findings suggest that polymorphisms of the NDUFV2 gene may be one of the genetic risk factors for bipolar disorder. © 2003 Wiley‐Liss, Inc.
Association analysis of MAOA and COMT with neuroticism assessed by peers
Authors: Eley Thalia C. , Tahir Eda , Angleitner Alois , Harriss Kaveri , McClay Joseph , Plomin Robert , Riemann Rainer , Spinath Frank , Craig Ian 
Published: June 2003

AbstractThere are several reported associations between depressive disorders, panic disorder, and obsessive–compulsive disorder (OCD) and a variety of polymorphisms in the monoamine oxidase A (MAOA) gene. Associations have also been reported between the catechol‐O‐methyltransferase (COMT) gene and both OCD and bipolar depression. However, the role of these markers has not been explored for the personality trait of neuroticism (N), a normally distributed quantitative trait, which is highly genetically correlated with anxiety and depression and may be a vulnerability to either type of disorder. We explored the possible role of MAOA, COMT, and their interaction on N using a selected extremes design. From a sample of 2,085 individuals, each assessed for N by two independent peers rather than using self‐report questionnaires, we selected 57 individuals from the top 10% of scores, and 62 individuals from the bottom 10%. Using selected extreme low subjects as the controls, rather than an unselected control group gives roughly twice the power of a standard case‐control design. We typed a functional variable number tandem repeat (VNTR) in the MAOA gene promoter, and a functional polymorphism in the coding region of the COMT gene. Two novel alleles in the MAOA VNTR were identified on the basis of their size, and their structure examined by sequencing analysis. We found weak evidence for association with COMT genotype, when the females and males were considered separately, and for MAOA genotype in males only. There was no significant interaction between COMT and MAOA. © 2003 Wiley‐Liss, Inc.
Detailed analysis of PRODH and PsPRODH reveals no association with schizophrenia
Authors: Williams H.J. , Williams N. , Spurlock G. , Norton N. , Zammit S. , Kirov G. , Owen M.J. , O'Donovan M.C. 
Published: June 2003

AbstractPeople with deletion of the chromosome 22q11 region associated with velo cardio‐facial syndrome (VCFS) have a remarkably high risk of developing schizophrenia. Recently, the gene proline dehydrogenase (PRODH) which maps to 22q11 and is also an excellent functional candidate gene for psychosis, has been reported to show genetic association with schizophrenia. We have screened all the exons and adjacent intronic sequences of PRODH for the presence of sequence variation in 14 DSM IV schizophrenic subjects. Similarly, we also screened all putative exons of a sequence that is similar to proline dehydrogenase (PsPRODH) and which also maps within the deleted region. A total of nine single nucleotide polymorphisms (SNPs) were identified in PRODH, eight of which were exonic, while in PsPRODH, five SNPs were identified, one of which was in a putative exon. All samples were tested for association in a pooled sample of 368 DSM IV diagnosed schizophrenic subjects and 368 matched controls. None of the variants identified in PRODH gave even modest evidence for allelic association (P < 0.1). In PsPRODH, two variants (−3864G > A and 226G > A) gave P values < 0.1. These were individually genotyped in the same subjects that had been used to construct the pools. Although a trend for association was confirmed, neither showed evidence for association at the P ≤ 0.05 level. These results do not suggest that PRODH or PsPRODH contribute to the aetiology of schizophrenia, and that the putative schizophrenia susceptibility gene in 22q11 remains unknown. © 2003 Wiley‐Liss, Inc.
Anwendung und Grenzen kristallographischer Daten im strukturbezogenen Liganden‐ und Wirkstoff‐Design
Authors: Davis Andrew M. , Teague Simon J. , Kleywegt Gerard J. 
Published: June 2003

AbstractStrukturbezogenes Design konzentriert sich auf die Optimierung der Ligandenaffinität, aber ein erfolgreiches Wirkstoff‐Design erfordert auch die Optimierung anderer Eigenschaften. Die Informationen zur Protein‐Ligand‐Struktur stammen meist aus der Kristallstrukturanalyse. Unsicherheiten, die während der Entwicklung eines Atommodells aus der experimentell erhaltenen Elektronendichte eingeführt werden, lassen sich manchmal nur eingeschränkt beurteilen. Ungenauigkeiten im Atommodell können aber erhebliche Konsequenzen haben, wenn das Modell anschließend als Grundlage für manuelles Design, Docking‐ und Scoring‐Rechnungen und virtuelles Screening dient. Manche Ansätze im strukturbezogenen Design nutzen inzwischen das Durchmustern von Substanzbibliotheken mit NMR‐spektroskopischen und röntgenographischen Methoden, um kleine polare Template zu identifizieren und anschließend zu optimieren. Nach diesen leitstrukturähnlichen Verbindungen wird auch mit dem moderneren Hochdurchsatz‐Screening gesucht.