Linkage on chromosome 14 in a genome-wide linkage study of a broad anxiety phenotype.

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

Several linkage studies on anxiety have been carried out in samples ascertained through probands with panic disorder. The results indicated that using a broad anxiety phenotype instead of a DSM-IV anxiety disorder diagnosis might enhance the chance of finding a linkage signal. In the current study, a genome-wide linkage analysis was performed on anxiety measured with a self-report questionnaire whose scores are highly correlated with DSM-IV anxiety disorders. The self-report questionnaire was included in five surveys of a longitudinal study of the Netherlands Twin Register. Genotype and phenotype data were available for 1602 twins and siblings. To estimate identity by descent , additional genotype data for 564 parents and 22 siblings were used. Linkage analyses were carried out using MERLIN-regress on the average anxiety scores across time. A linkage signal (logarithm of odds score 3.4, empirical P-value 0.07) was obtained at chromosome 14 for marker D14S65 at 105 cM (90% confidence interval, 99-115 cM bounded by markers D14S1434 and D14S985). This finding replicates a linkage finding for a broad anxiety phenotype in a clinically based sample, indicating that the region might harbor a quantitative trait locus associated with the whole spectrum of general anxiety, that is from the normal to the clinical range. Moreover, genome-wide linkage and association studies on emotionality in mice obtained significant results in a syntenic region on mouse chromosome 12. Two homolog genes lie in this region -Dlk1 (delta-like 1 homolog, Drosophila) and Rtl1 (retrotransposon-like 1). Future association studies of these genes are warranted. © 2008 Nature Publishing Group All rights reserved.
Original languageEnglish
Pages (from-to)84-89
JournalMolecular Psychiatry
Volume13
Issue number1
DOIs
Publication statusPublished - 2008

Fingerprint

Chromosomes, Human, Pair 14
Anxiety
Genome
Phenotype
Anxiety Disorders
Diagnostic and Statistical Manual of Mental Disorders
Self Report
Genotype
Chromosomes, Human, Pair 12
Retroelements
Quantitative Trait Loci
Genome-Wide Association Study
Panic Disorder
Genetic Markers
Netherlands
Genes
Drosophila
Longitudinal Studies
Confidence Intervals
Surveys and Questionnaires

Cite this

@article{b3fa17e4bc4b4a2eb3700927475c6a76,
title = "Linkage on chromosome 14 in a genome-wide linkage study of a broad anxiety phenotype.",
abstract = "Several linkage studies on anxiety have been carried out in samples ascertained through probands with panic disorder. The results indicated that using a broad anxiety phenotype instead of a DSM-IV anxiety disorder diagnosis might enhance the chance of finding a linkage signal. In the current study, a genome-wide linkage analysis was performed on anxiety measured with a self-report questionnaire whose scores are highly correlated with DSM-IV anxiety disorders. The self-report questionnaire was included in five surveys of a longitudinal study of the Netherlands Twin Register. Genotype and phenotype data were available for 1602 twins and siblings. To estimate identity by descent , additional genotype data for 564 parents and 22 siblings were used. Linkage analyses were carried out using MERLIN-regress on the average anxiety scores across time. A linkage signal (logarithm of odds score 3.4, empirical P-value 0.07) was obtained at chromosome 14 for marker D14S65 at 105 cM (90{\%} confidence interval, 99-115 cM bounded by markers D14S1434 and D14S985). This finding replicates a linkage finding for a broad anxiety phenotype in a clinically based sample, indicating that the region might harbor a quantitative trait locus associated with the whole spectrum of general anxiety, that is from the normal to the clinical range. Moreover, genome-wide linkage and association studies on emotionality in mice obtained significant results in a syntenic region on mouse chromosome 12. Two homolog genes lie in this region -Dlk1 (delta-like 1 homolog, Drosophila) and Rtl1 (retrotransposon-like 1). Future association studies of these genes are warranted. {\circledC} 2008 Nature Publishing Group All rights reserved.",
author = "C.M. Middeldorp and J.J. Hottenga and P.E. Slagboom and P.F. Sullivan and {de Geus}, E.J.C. and D. Posthuma and G. Willemsen and D.I. Boomsma",
year = "2008",
doi = "10.1038/sj.mp.4002061",
language = "English",
volume = "13",
pages = "84--89",
journal = "Molecular Psychiatry",
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}

Linkage on chromosome 14 in a genome-wide linkage study of a broad anxiety phenotype. / Middeldorp, C.M.; Hottenga, J.J.; Slagboom, P.E.; Sullivan, P.F.; de Geus, E.J.C.; Posthuma, D.; Willemsen, G.; Boomsma, D.I.

In: Molecular Psychiatry, Vol. 13, No. 1, 2008, p. 84-89.

Research output: Contribution to JournalArticleAcademicpeer-review

TY - JOUR

T1 - Linkage on chromosome 14 in a genome-wide linkage study of a broad anxiety phenotype.

AU - Middeldorp, C.M.

AU - Hottenga, J.J.

AU - Slagboom, P.E.

AU - Sullivan, P.F.

AU - de Geus, E.J.C.

AU - Posthuma, D.

AU - Willemsen, G.

AU - Boomsma, D.I.

PY - 2008

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N2 - Several linkage studies on anxiety have been carried out in samples ascertained through probands with panic disorder. The results indicated that using a broad anxiety phenotype instead of a DSM-IV anxiety disorder diagnosis might enhance the chance of finding a linkage signal. In the current study, a genome-wide linkage analysis was performed on anxiety measured with a self-report questionnaire whose scores are highly correlated with DSM-IV anxiety disorders. The self-report questionnaire was included in five surveys of a longitudinal study of the Netherlands Twin Register. Genotype and phenotype data were available for 1602 twins and siblings. To estimate identity by descent , additional genotype data for 564 parents and 22 siblings were used. Linkage analyses were carried out using MERLIN-regress on the average anxiety scores across time. A linkage signal (logarithm of odds score 3.4, empirical P-value 0.07) was obtained at chromosome 14 for marker D14S65 at 105 cM (90% confidence interval, 99-115 cM bounded by markers D14S1434 and D14S985). This finding replicates a linkage finding for a broad anxiety phenotype in a clinically based sample, indicating that the region might harbor a quantitative trait locus associated with the whole spectrum of general anxiety, that is from the normal to the clinical range. Moreover, genome-wide linkage and association studies on emotionality in mice obtained significant results in a syntenic region on mouse chromosome 12. Two homolog genes lie in this region -Dlk1 (delta-like 1 homolog, Drosophila) and Rtl1 (retrotransposon-like 1). Future association studies of these genes are warranted. © 2008 Nature Publishing Group All rights reserved.

AB - Several linkage studies on anxiety have been carried out in samples ascertained through probands with panic disorder. The results indicated that using a broad anxiety phenotype instead of a DSM-IV anxiety disorder diagnosis might enhance the chance of finding a linkage signal. In the current study, a genome-wide linkage analysis was performed on anxiety measured with a self-report questionnaire whose scores are highly correlated with DSM-IV anxiety disorders. The self-report questionnaire was included in five surveys of a longitudinal study of the Netherlands Twin Register. Genotype and phenotype data were available for 1602 twins and siblings. To estimate identity by descent , additional genotype data for 564 parents and 22 siblings were used. Linkage analyses were carried out using MERLIN-regress on the average anxiety scores across time. A linkage signal (logarithm of odds score 3.4, empirical P-value 0.07) was obtained at chromosome 14 for marker D14S65 at 105 cM (90% confidence interval, 99-115 cM bounded by markers D14S1434 and D14S985). This finding replicates a linkage finding for a broad anxiety phenotype in a clinically based sample, indicating that the region might harbor a quantitative trait locus associated with the whole spectrum of general anxiety, that is from the normal to the clinical range. Moreover, genome-wide linkage and association studies on emotionality in mice obtained significant results in a syntenic region on mouse chromosome 12. Two homolog genes lie in this region -Dlk1 (delta-like 1 homolog, Drosophila) and Rtl1 (retrotransposon-like 1). Future association studies of these genes are warranted. © 2008 Nature Publishing Group All rights reserved.

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