Linkage on chromosome 14 in a genome-wide linkage study of a broad anxiety phenotype.
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.
Middeldorp
C M
CM
Department of Biological Psychology, VU University Amsterdam, Amsterdam, The Netherlands. cm.middeldorp@psy.vu.nl
Hottenga
J-J
JJ
Slagboom
P E
PE
Sullivan
P F
PF
de Geus
E J C
EJ
Posthuma
D
D
Willemsen
G
G
Boomsma
D I
DI
D000367:Age Factors; D001007:Anxiety / Q000235:genetics*; D001008:Anxiety Disorders / Q000235:genetics*; D002874:Chromosome Mapping; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D006801:Humans; D008126:Lod Score; D008137:Longitudinal Studies; D008297:Male; D010375:Pedigree; D010641:Phenotype; D012647:Self-Assessment; D012737:Sex Factors
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