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V Vieland

Publications and source records attributed to V Vieland.

10 recordsLinked to original sources

Incorporating language phenotypes strengthens evidence of linkage to autism.

We investigated the effect of incorporating information about proband and parental structural language phenotypes into linkage analyses in the two regions for which we found the highest signals in our first-stage affected sibling pair genome screen: chromosomes 13q and 7q. We were particularly interested in following up on our chromosome 7q finding in light of two prior reports of linkage of this region to developmental language disorder, since one of the diagnostic criteria for autism is absent or abnormal language development. We hypothesized that if the language phenotype were genetically relevant to linkage at the chromosome 7q locus, then incorporating parents phenotypes would increase the signal at that locus, and most of the signal would originate from the subset of families in which both probands had severe language delay. The results support these hypotheses. The linkage signals we obtained on chromosome 7q as well as at least one signal on chromosome 13q are mainly attributable to the subgroup of families in which both probands had language delay. This became apparent only when the parents' history of language-related difficulties was also incorporated into the analyses. Although based on our data, we were not able to distinguish between epistasis or heterogeneity models, we tentatively concluded that there may be more than one autism susceptibility locus related to language development.

Autistic Disorder↗

Combined multipoint analysis of multiple asthma data sets based on the posterior probability of linkage.

In the presence of multiple data sets, an important issue is how to best measure the overall evidence for linkage across data sets. Previously, we advocated the use of the posterior probability of linkage (PPL) for this purpose [Vieland, Am J Hum Genet 63:947-54, 1998; Wang et al., Ann Hum Genet 64:533-53, 2000; Vieland et al., Hum Hered 51:199-208, 2001]. In this paper, we propose a critical modification of our earlier two-point PPL in order to handle multiple-point calculations. The proposed modification is then applied to the genome-screen data sets and the COAG chromosome 5 data sets provided by GAW 12. We find linkage signals at location (in the order of the strength of the signal) 45 cM on chromosome 6, 23 cM on chromosome 20, and 30 cM on chromosome 1. No linkage signal is found on chromosome 5.

Adult↗

Report of the Chromosome 5 Workshop of the Sixth World Congress on Psychiatric Genetics.

The Chromosome 5 Workshop heard new data on a schizophrenia susceptibility locus in the 5q23.3-q31.1 region. Sixty-two pedigrees from Finland gave a lod score of 1.36 at the CSF1R locus approximately 14 cM distal to IL9/D5S393, where positive results from three pedigree collections converged at the 1997 workshop. Though positive at CSF1R, the new data were only weakly positive at the IL9 (lod 0.46) and D5S393 (lod 0.07) loci themselves. The workshop also reviewed new evidence in the 5p14.1-p13.1 region, where a large pedigree of schizophrenia of Puerto Rican extraction has suggested a susceptibility locus with a maximum lod score at D5S111. Twenty-one new pedigrees multiplex for schizophrenia in African Americans gave positive lod scores at D5S111 and flanking loci. In bipolar illness five genetically related pedigrees from the Saguenay-Lac-St. Jean region of Quebec identified a region of interest at 5q31.3-q35.1. This region overlaps with the D5S423 locus and includes the D5S812 locus and the 5q34 region, all of which are consistent with linkage in at least one other study.

Bipolar Disorder↗

A Bayesian approach to replication of linkage findings.

A novel Bayesian approach to replication studies, allowing for locus heterogeneity, is introduced. Compared with currently used approaches to replication, it offers a natural way to accumulate evidence across independently collected data sets and yields more interpretable results. Using for replicates (one as initial study and the other three as replication studies) from Problem 2 of the Genetic Analysis Workshop 11 data, we show the performance of this method. All four disease susceptibility loci (D1G009, D1G024, D3G045, D5G035) are identified and accurately mapped, with no false positive signals.

Bayes Theorem↗

Chromosome 5 workshop.

In schizophrenia, evidence consistent with linkage in the 5q23.3-q31.1 region emerged from three independent samples. In addition, a moderately retarded woman with schizophrenia with an interstitial deletion overlapping this region was reported at the workshop. A second region of interest for schizophrenia is the 5p14.1-p13.1 region, where lod scores as high as 4.37 were found in one pedigree. Chromosome 5p15 gave a non-parametric linkage (NPL) score of 2.18 (p < 0.02) in one study. Several genome scans have not found evidence of excess allele sharing in these regions, although in most cases the genome scans did not include the markers that had resulted in provisional evidence of linkage. A large pedigree of bipolar illness has shown provisional evidence of linkage at, or near, the dopamine transporter locus at 5p15.3; the maximum lod score obtained was 2.72 at D5S417. In other regions, a genome scan of bipolar disorder gave NPL scores of 2.98 at D5S812 and 3.76 at D5S423. The third disorder of interest is attention deficit hyperactivity disorder (ADHD) because two studies have reported an association with the 480 bp allele at the dopamine transporter locus. A poster presented at the Congress reported a failure to replicate the association in a sample with considerable power to detect the effect size previously reported.

Attention Deficit Disorder with Hyperactivity↗

A new statistical test for age-of-onset anticipation: application to bipolar disorder.

The discovery of expanding microsatellite repeat mechanisms for a variety of diseases has spurred renewed interest in testing for genetic anticipation in complex diseases. However, standard statistical methods can be shown to be inappropriate for this purpose. We derive a new statistical test for comparing mean age of onset in parents with mean age of onset in children, based on a random sample of affected parent-child pairs. This test incorporates the right-truncation of the age-of-onset distributions and utilizes age-at-interview information. We illustrate the use of the test by application to bipolar affective disorder data. In this example, the correct p-value is 0.014 whereas the results based on the biased estimates give a p-value of 0.0001 [McInnis et al., 1993]. We also briefly consider the effects of ascertainment bias when parent-child pairs are obtained from samples collected for purposes of linkage analysis.

Age of Onset↗

The impact of curriculum-based suicide prevention programs for teenagers.

The impact of three school-based suicide prevention programs was assessed by comparing attitudes and knowledge of 758 9th and 10th graders with those of 680 control pupils, matched on age, ethnicity, and socioeconomic status at the school level, who did not receive the programs. Evaluations were conducted before exposure to the programs and again 1 month later. A large majority of students knew and subscribed to some of the more important program goals before exposure to the program. There was little evidence of program impact among the minority that did not. Most students were interested by the programs, and positive reactions were more common among female and minority students.

Adolescent↗

The impact of curriculum-based suicide prevention programs for teenagers: an 18-month follow-up.

In a long-term follow-up of a study designed to assess the impact of school-based suicide prevention curricula on high school students, a group of 174 students from two high schools who were exposed to a prevention program were compared with a group of 207 control students from two additional high schools who were not exposed to the curriculum. A questionnaire, designed to measure the effects of the prevention program on actual help-seeking behaviors and suicide morbidity during the follow-up period, was administered 18 months after delivery of the program. The study failed to find convincing evidence of any program effect.

Adolescent↗

Adolescent suicide attempters. Response to suicide-prevention programs.

As part of a controlled evaluation of three suicide-prevention curricula delivered to 1438 ninth- and 10th-grade students, 63 adolescents were identified as having made a suicide attempt. Their attitudes about suicide and help seeking were compared with those of 910 nonattempters drawn from the same population. Reaction to the prevention program was assessed by comparing the responses of the 35 attempters exposed to the programs with responses of 524 exposed nonattempters. The impact of the programs was assessed by comparing 35 exposed attempters with 28 attempters from a control group. Self-identified attempters were less likely to endorse views consistent with the curricula at baseline, but there was little evidence that the programs were successful in influencing these views. There was some evidence that previous attempters were more upset by the programs than their nonattempter peers. The prevalence of suicide attempts as defined in this study by self-report was higher than that reported in studies using interview techniques.

Adolescent↗