bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of the C766T polymorphism of the low‐density lipoprotein receptor‐related protein gene with Alzheimer's disease
Authors: Kölsch Heike , Ptok Ursula , Mohamed Iman , Schmitz Sandra , Rao Marie Luise , Maier Wolfgang , Heun Reinhard 
Published: July 2003

AbstractThe low‐density lipoprotein receptor‐related protein (LRP) is one of the most important cholesterol receptors in the brain. Gene variation of its ligand, apolipoprotein E, is a major genetic risk‐factor for Alzheimer's disease (AD). The C‐allele of the silent C766T polymorphism in exon 3 of the LRP gene might be associated with AD, however, results are conflicting and thus discussed controversially. Consequently, we compared the prevalence of this polymorphism in a homogenous cohort of patients with AD and control subjects. We found that carriers of a C‐allele were at lower risk of AD; in agreement with this observation, AD patients who were carriers of a C‐allele presented with a later age at onset of the disease than carriers of the TT genotype. These data suggest that LRP polymorphism influences the risk as well as the age at onset of AD. Our results contrast with other studies which described the C‐allele to be a risk‐factor for AD, but are in line with a recent publication on the effect of LRP polymorphism on longevity and on the risk for coronary artery disease. Further research on LRP polymorphisms is needed to evaluate their effects on the risk of AD, on coronary artery disease and on longevity. © 2003 Wiley‐Liss, Inc.
Report from the 4th International Meeting of the Attention Deficit Hyperactivity Disorder Molecular Genetics Network
Authors: Faraone Stephen V. 
Published: July 2003

AbstractInvestigators from around the world have convened annually since 1999 to share their work on the molecular genetic basis of attention deficit hyperactivity disorder (ADHD). The 4th meeting of the ADHD Molecular Genetics Network was held in May 2002. This conference began with a discussion of ongoing and proposed collaborative projects. Ongoing collaborations include the International Multi‐Center ADHD Genetics (IMAGE) project, a study of additive and interactive effects of DAT1 and DRD4 on ADHD and a meta‐analysis of association studies of ADHD and the DRD5 gene. A new collaborative project regarding DNA pooling was also proposed. Over 20 investigators presented recent findings from their individual research sites. Participants also broke up into working groups to discuss additional projects and topics of mutual interest, including population genetic studies using dimensional phenotypic data and a QTL approach, endophenotypes for ADHD and the genetics of ADHD in adults. Finally, participant feedback was obtained about the utility of the ADHD Molecular Genetics Network conferences and the e‐mail network. Although technological and statistical advances in the field of molecular genetics have allowed researchers to begin to identify specific genes that are associated with ADHD, continued collaborative efforts are needed to fully elucidate the genetic underpinnings of this complex phenotype. Data collected at the current conference indicate that the ADHD Molecular Genetics Network has facilitated new collaborative as well as single‐site projects among ADHD researchers. © 2003 Wiley‐Liss, Inc.
CAG‐Repeat length in exon 1 of KCNN3 does not influence risk for schizophrenia or bipolar disorder: A meta‐analysis of association studies
Authors: Glatt Stephen J. , Faraone Stephen V. , Tsuang Ming T. 
Published: July 2003

AbstractSchizophrenia and bipolar disorder both show some evidence for genetic anticipation. In addition, significant expansion of anonymous CAG repeats throughout the genome has been detected in both of these disorders. The gene KCNN3, which codes for a small/intermediate conductance, calcium‐regulated potassium channel, contains a highly polymorphic CAG‐repeat array in exon 1. Initial evidence for association of both schizophrenia and bipolar disorder with increased CAG‐repeat length of KCNN3 has not been consistently replicated. In the present study, we performed several meta‐analyses to evaluate the pooled evidence for association with CAG‐repeat length of KCNN3 derived from case‐control and family‐based studies of both disorders. Each group of studies was analyzed under two models, including a test for direct association with repeat length, and a test for association with dichotomized repeat‐length groups. No evidence for a linear relationship between disease risk and repeat length was observed, as all pooled odds ratios approximated 1.0. Results of dichotomized allele‐group analyses were more variable, especially for schizophrenia, where case‐control studies found a significant association with longer repeats but family‐based studies implicated shorter alleles. The results of these meta‐analyses demonstrate that the risks for both schizophrenia and bipolar disorder are largely, if not entirely, independent of CAG‐repeat length in exon 1 of KCNN3. This study cannot exclude the possibility that some aspect of this polymorphism, such as repeat‐length disparity in heterozygotes, influences risk for these disorders. Further, it remains unknown if this polymorphism, or one in linkage disequilibrium with it, contributes to some distinct feature of the disorder, such as symptom severity or anticipation. © 2003 Wiley‐Liss, Inc.
Analysis of transmission of novel polymorphisms in the somatostatin receptor 5 (SSTR5) gene in patients with autism
Authors: Lauritsen Marlene B. , Nyegaard Mette , Betancur Catalina , Colineaux Catherine , Josiassen Trine L. , Kruse Torben A. , Leboyer Marion , Ewald Henrik 
Published: July 2003

AbstractInfantile autism is a pervasive developmental disorder with a strong genetic component. The mode of inheritance appears to be complex and no specific susceptibility genes have yet been identified. Chromosome 16p13.3 may contain a susceptibility gene based on findings from genome scans and reports of chromosome abnormalities in individuals with autism. The somatostatin receptor 5 (SSTR5) gene is located on chromosome 16p13.3 and is thus a positional candidate gene for autism. SSTR5 may also be a functional candidate gene for autism because somatostatin inhibits growth hormone secretion, and increased growth hormone response has been reported in some individuals with autism. Moreover, the somatostatinergic system interacts with the dopaminergic system, which has been hypothesized to be involved in the etiology of autism; in particular, somatostatin secretion is regulated by dopamine, and the dopamine D2 receptor and the SSTR5 receptor interact to form a receptor complex with enhanced functional activity. In the present study, we tested whether the alleles of twelve new single nucleotide polymorphisms (SNPs) in the SSTR5 gene were preferentially transmitted, using the transmission disequilibrium test (TDT) in a sample of 79 trios with autism (18 from Denmark and 61 from France). Furthermore, we combined four missense SNPs into haplotypes and searched for preferential transmission using the program TRANSMIT. No significant preferential transmission of the alleles and haplotypes of the twelve SNPs was found. Our results do not suggest the SSTR5 gene as a susceptibility gene for autism. © 2003 Wiley‐Liss, Inc.
Genome scan of the fifty‐six bipolar pedigrees from the NIMH genetics initiative replication sample: Chromosomes 4, 7, 9, 18, 19, 20, and 21
Authors: Willour Virginia L. , Zandi Peter P. , Huo Yuqing , Diggs Tyra L. , Chellis Jennifer L. , MacKinnon Dean F. , Simpson Sylvia G. , McMahon Francis J. , Potash James B. , Gershon Elliot S. , Reich Theodore , Foroud Tatiana , Nurnberger John I. , Raymond DePaulo J. , McInnis Melvin G. 
Published: July 2003

AbstractThe NIMH genetics initiative on bipolar disorder was established to collect uniformly ascertained bipolar pedigrees for genetic studies. In 1997, the four participating sites published a genome scan on the initial set of 97 bipolar pedigrees. Fifty‐six additional bipolar pedigrees have now been ascertained and evaluated. This replication pedigree set contains 354 genotyped subjects, including 139 bipolar I (BPI) subjects, five schizoaffective bipolar type SA/BP subjects, 41 bipolar II (BPII) subjects, and 43 recurrent unipolar (RUP) depression subjects. Our site has recently genotyped the replication study bipolar pedigrees using 107 microsatellite markers from chromosomes 4, 7, 9, 18, 19, 20, and 21. We are now reporting parametric and nonparametric linkage results from this effort. Multipoint nonparametric linkage analysis produced three candidate regions with allele sharing LOD scores ≥ 1.0. The linkage signal on 4q35 peaked between markers D4S3335 and D4S2390 with an allele sharing LOD score of 2.49. This finding exceeds standard criteria for suggestive linkage. Two additional loci approach suggestive linkage levels: the 4q32 finding had its maximum near marker D4S1629 with an allele sharing LOD score of 2.16, and the 20p12 finding peaked at D20S162 with an allele sharing LOD score of 1.82. Multipoint parametric linkage analysis produced similar findings. When we combined the genotype data from the original and the replication pedigree sets, 20p12 yielded a nonparametric LOD score of 2.38, which exceeds standard criteria for suggestive linkage, and a corresponding parametric HLOD score of 2.98. The combined analysis did not provide further support for linkage to 4q32 and 4q35. © 2003 Wiley‐Liss, Inc.
Genetic dissection of psychopathological symptoms: Insomnia in mood disorders and CLOCK gene polymorphism
Authors: Serretti Alessandro , Benedetti Francesco , Mandelli Laura , Lorenzi Cristina , Pirovano Adele , Colombo Cristina , Smeraldi Enrico 
Published: July 2003

AbstractWe investigated the possible effect of the 3111T/C CLOCK gene polymorphism on sleep disorders in a sample of 620 patients affected by major depressive disorder (MDD) and bipolar disorder (BP). We detected a significantly higher recurrence of initial (P = 0.0001), middle (P = 0.0009), and early (P = 0.0008) insomnia in homozygotes for the C variant and a similar trend concerning decreased need of sleep in BP (P = 0.0074). Other demographic and clinical features were found not related with CLOCK polymorphisms. This preliminary observation leads to hypothesize a possible involvement of the CLOCK gene polymorphism in the sleep disregulations in MDD and BP. Copyright © 2003 Wiley‐Liss, Inc.
D2 and D4 dopamine receptor gene polymorphisms and personality traits in a young Korean population
Authors: Lee Heon‐Jeong , Lee Hong‐Seock , Kim Yong‐Ku , Kim Leen , Lee Min Soo , Jung In‐Kwa , Suh Kwang‐Yoon , Kim Sangduk 
Published: July 2003

AbstractThe correlation between the D4 dopamine receptor gene (DRD4) and the D2 dopamine receptor gene (DRD2) polymorphisms was investigated with personality traits. For this study, homogeneous population consisting of 243 young alcohol‐ and drug‐naive Koreans who were blood‐unrelated with a mean age (±SD) of 13.87 (±0.30) years old was analyzed for the DRD4 and the DRD2 polymorphisms with their personality trait by Temperament and character inventory (TCI). The association between Novelty seeking (NS) score and DRD4 long alleles was only observed among the female subjects (t = 2.11, P = 0.037), but not in the male counter part. Female subjects who carried the DRD2 less frequent alleles (TaqI A1, TaqI B1, and Intron6 1) showed higher RD4 scores (dependence vs. independence) of Reward dependence (RD) than those without these alleles (P < 0.05). There was no interaction between DRD4 and DRD2 on the personality traits. These results, thus, confirmed the previous findings in which the long repeats of the DRD4‐exon III polymorphism are related to NS personality trait, and also suggested that the DRD2 less frequent alleles were also associated with the reward‐dependent trait. © 2003 Wiley‐Liss, Inc.
Association between human μ‐opioid receptor gene polymorphism, pain tolerance, and opioid addiction
Authors: Compton Peggy , Geschwind Daniel H. , Alarcón Maricela 
Published: July 2003

AbstractCentral to both pain responses and opioid addiction is activity at the μ‐opioid receptor. To explore the role of the μ‐opioid receptor gene (OPRM) in human pain tolerance and opioid addiction, we examined the relationships among OPRM genotype and experimental pain tolerance in opioid addicts in methadone treatment (n = 50) and healthy normal controls (n = 59). Pain phenotype (pain tolerant vs. pain intolerant) was operationalized as tolerance to a standardized noxious stimulus (either thermal or mechanical), and dichotomized based on distribution. One microsatellite and two single nucleotide polymorphisms, A118G and C17T, in exon 1 were typed to study the OPRM gene. Although the established relationship between the phenotypes of opioid addiction and pain intolerance was validated (P = 0.02), genotype differed neither between addict‐affected vs. control, nor pain tolerant vs. intolerant subjects. The variant A118G was absent in all individuals and the C17T polymorphism appeared in only three African‐American individuals (two addicts and one control). The absence of this polymorphism, the small sample size and the heterogeneous ethnic backgrounds of participants in the pilot study allow only tentative conclusions based on the results, thus the role of the opioid receptor in pain and opioid reward response remains uncertain. © 2003 Wiley‐Liss, Inc.
Tumor necrosis factor haplotype analysis amongst schizophrenia probands from four distinct populations in the Asia‐Pacific region
Authors: Handoko Herlina Y. , Nancarrow Derek J. , Hayward Nicholas K. , Ohaeri Jude U. , Aghanwa Henry , McGrath John J. , Levinson Douglas F. , Johns Christopher , Walters Marilyn K. , Nertney Deborah A. , Srinivasan T.N. , Thara R. , Mowry Bryan J. 
Published: July 2003

AbstractA single nucleotide polymorphism (TNF−308A) within the promoter region of the gene encoding tumor necrosis factor (TNF), has been significantly associated with schizophrenia in a study of Italian patients and control subjects Boin et al. [2001: Mol Psychiatry 6:79–82]. We have applied case‐control analyses to examineTNFpromoter haplotypes (containingTNF−308and two additional promoter variants:TNF−376andTNF−238) in four schizophrenia cohorts drawn from Australian, Indian Fijian, Indigenous Fijian, and Brahmin populations. In addition, we have applied the sibling transmission disequilibrium (STD) test to promoter haplotypes within 81 trios drawn from Australian Caucasian pedigrees with multiple schizophrenia cases, and 86 trios drawn from the Brahmin population of Tamil Nadu province in Southern India. Within each of these cohorts, we found no evidence of recombination between these tightly linked promoter variants, supporting previous studies which demonstrated that only a subset of the eight possible haplotypes exist. Of the four observed haplotypes, we and others have observed only one carries theTNF−308Avariant allele. We report no significant differences inTNFpromoter haplotype frequencies between the patient and control groups within each population, although the Indian Fijian cohort showed a trend towards reducedTNF−308Aalleles amongst schizophrenia cases (P = 0.07). We found no evidence of bias inTNFpromoter haplotype transmission to schizophrenia probands. Very similar results were obtained when only theTNF−308polymorphism was considered. Taken together, these data provide no support for the involvement ofTNFpromoter variantsTNF−308,TNF−376, andTNF−238in schizophrenia susceptibility within four ethnically distinct cohorts. © 2003 Wiley‐Liss, Inc.
Association of a haplotype in the serotonin 5‐HT4 receptor gene (HTR4) with Japanese schizophrenia
Authors: Suzuki T. , Iwata N. , Kitamura Y. , Kitajima T. , Yamanouchi Y. , Ikeda M. , Nishiyama T. , Kamatani N. , Ozaki N. 
Published: July 2003

AbstractThe serotonin 5‐HT4 receptor (5‐HT4) is implicated in cognitive function, of which impairment is hypothesized as one of the core disturbances of schizophrenia. Linkage analysis shows that 5q33.2, in which HTR4 is located, is schizophrenia‐susceptibility loci. We therefore hypothesized that variation in the 5‐HT4 receptor gene (HTR4) modifies genetic susceptibility to schizophrenia. HTR4 coding regions and introns that include the branch sites of HTR4 were investigated in 96 unrelated Japanese schizophrenics using denaturing high‐performance liquid chromatography analysis. One silent single nucleotide polymorphism (SNP) within the coding region and six intronic SNPs were detected. 353 + 6G > A was located in the branch site that could be effect to RNA splicing. None of the four SNPs, in which rare‐allele frequencies were more than 10% was associated with 189 schizophrenics, in comparison to 299 controls. However, a highly significant association between schizophrenia and haplotype A‐T (OR = 0.13 [0.03–0.58]) was detected. These findings suggest that haplotype A‐T itself may inhibit the occurrence of schizophrenia, or that another susceptible genetic variants may exist within linkage disequilibrium. © 2003 Wiley‐Liss, Inc.
The association of the D2S2944 124 bp allele with recurrent early onset major depressive disorder in women
Authors: Philibert Robert , Caspers Kristin , Langbehn Douglas , Troughton Edward P. , Yucuis Rebecca , Sandhu Harinder K. , Cadoret Remi J. 
Published: July 2003

AbstractMajor depressive disorder (MDD) and substance use disorders (SUD) are complex behavioral disorders with 40–50% heritability. Recently, Zubenko and colleagues reported that the 124 bp allele of D2S2944, a tetranucleotide repeat marker on 2q35, is strongly associated with recurrent, early onset MDD (RE‐MDD) and alcohol use disorders in women. To test this hypothesis, we examined the association of the 124 bp allele in a subset of 171 adoptees from the Iowa Adoption Studies, a population with high rates of MDD and SUD. We report that in our population, the 124 bp allele significantly associated with RE‐MDD in women. There was slight evidence of an increased of SUD in women with the 124 bp allele with the rate of cannabis use disorders reaching statistical significance (P < 0.04) before correction for multiple comparisons. Given the history of prior studies implicating 2q35 as a locus encoding vulnerability to co‐morbid alcoholism and depression, these findings strongly suggest that sequence variation conveying increased susceptibility to MDD and possibly SUD is in close proximity to D2S2944. © 2003 Wiley‐Liss, Inc.
A psychometrically derived impulsive trait related to a polymorphism in the serotonin transporter gene‐linked polymorphic region (5‐HTTLPR) in a japanese nonclinical population: Assessment by the barratt impulsiveness scale (BIS)
Authors: Sakado Kaoru , Sakado Miwako , Muratake Tatsuyuki , Mundt Christoph , Someya Toshiyuki 
Published: July 2003

AbstractAlthough a number of studies have shown that human impulsive traits are associated with indices of central serotonin function, few researchers have investigated the relationship between a polymorphism in the serotonin transporter gene‐linked region (5‐HTTLPR) and a psychometrically derived impulsive trait. We determined the 5‐HTTLPR polymorphism in 123 employed Japanese male adults using the polymerase chain reaction. The distribution of allelic frequency was determined and also investigated the relationship of the 5‐HTTLPR polymorphism to a impulsive trait as measured by the Barratt Impulsiveness Scale, 11th version (BIS‐11). The distribution of allelic frequency was found to be almost identical to that previously reported in Japanese (the frequency for the long (L)/L, L/short (S), and S/S genotypes was: 3, 28, and 68%, respectively). In a comparison between the genotype groups, the S/S genotype group significantly higher scored for the total BIS‐11 and the subscale attentional impulsiveness than the L/S + L/L genotype group. These findings suggest that individuals with a homozygous S‐allele may be more impulsive than those with the other genotype. © 2003 Wiley‐Liss, Inc.
Linkage disequilibrium and haplotype analysis between serotonin receptor 1B gene variations and subtypes of alcoholism
Authors: Sinha Rashmi , Cloninger C. Robert , Parsian Abbas 
Published: July 2003

AbstractA number of studies have reported a possible association between serotonergic pathway genes and alcoholism. A silent polymorphism (G to C substitution) in the gene encoding the autoreceptor 5‐HT1B was linked to antisocial alcoholism in Finnish and an American Indian populations [Lappalainen et al., 1998: Arch Gen Psychiatry 55:989–994]. Several other polymorphisms of this gene have been investigated for their association with neuropsychiatric disorders. In the present study, a sample of 133 alcoholics without and 39 alcoholics with medical complications, and 88 normal controls was screened for three single nucleotide polymorphisms (SNPs), G861C, G261T, and C129T, in the 5‐HT1B gene. The goal was to investigate their association with the disease, to measure the strength of linkage disequilibrium (LD) between the SNPs, and to compare haplotype frequencies between alcoholic groups and normal controls. Data was also analyzed on the basis of Type I (n = 47) and Type II (n = 85) alcoholism. There was no significant difference in the allele frequencies or the genotype distribution between any alcoholic groups, alcoholic subgroups, and controls for any polymorphism. G861C and C129T polymorphisms were in complete LD. The pattern of distribution of haplotypes was similar in patients and controls. It is concluded that these SNPs are not playing any direct role in the development of susceptibility to alcoholism in our patient sample. © 2003 Wiley‐Liss, Inc.
Children at familial risk for Tourette's disorder: Child and parent diagnoses
Authors: McMahon William M. , Carter Alice S. , Fredine Nancy , Pauls David L. 
Published: July 2003

AbstractTourette's disorder (TD) is a neuropsychiatric disorder that onsets in childhood and appears to result from an interaction of genetic and environmental factors. The goal of the current prospective longitudinal study is to examine the onset of TD in offspring of parents with TD. At‐risk children and control children were enrolled between the ages of 3 and 6 years and prospectively studied with yearly structured assessments over intervals of 2–5 years. Of 34 at‐risk children free of tics at baseline, 10 (29%) subsequently developed a tic disorder, including 3 with TD. None of the 13 control children developed a tic disorder (P = 0.045). OCD or subclinical OCD emerged in 11 cases but no controls (P = 0.021). Finally, ADHD occurred in 14 at‐risk children but no controls (P = 0.005). When at‐risk families were dichotomized into bilineal or unilineal categories, rates of TD in children with two affected parents were three times the rate observed for children with one affected parent. These findings support the hypothesis that at least some cases of TD result from a complex genetic etiology. TD, OCD, and ADHD are significantly increased in children with TD parents. Furthermore, the risk is even greater when both parents are affected. Finally, our diagnosis of tic disorders in 21% of subjects initially reported by parents to be unaffected affirms the value of structured clinical assessments. © 2003 Wiley‐Liss, Inc.