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.

Heritability and Genome-Wide Linkage Scan of Subjective Happiness

“…The region on chromosome 1 (p12) also harbors several protein-coding genes (for example WARS2, PI4KB and SCA19), but these also do not play a plausible role in the variance of happiness. Although happiness is often seen as the counterpart of depression, the regions with suggestive linkage for happiness have not been reported for depression so far (e.g., Middeldorp et al, 2008). Furthermore the regions on chromosome 1 and 19 have also not been suggested in a linkage scan for borderline personality disorder features (Distel et al 2008) and a linkage scan for Neuroticism (Wray et al, 2008).…”

Sequence variations of ABCB1, SLC6A2, SLC6A3, SLC6A4, CREB1, CRHR1 and NTRK2: association with major depression and antidepressant response in Mexican-Americans

“…Current data point out to roles for genes involved in drug transport, serotonin neurotransmission, neurotrophin signaling and response to stress. Promising linkage results are located in several chromosomes, 3 which highlight the multilocus nature of the genetic vulnerability to MDD.…”

TMEM132D, a new candidate for anxiety phenotypes: evidence from human and mouse studies

“…Linkage studies have revealed several potentially interesting loci located on chromosomes 1, 12 and 14. [4][5][6] Of these, only the locus on chromosome 1q has been identified by different groups independently. 4,5,7 Candidate gene association studies so far have mostly tested monoamine-and neuropeptiderelated genes, giving inconsistent results, which often failed to replicate in independent studies, most likely because of phenotypic diversity, genetic heterogeneity and small sample sizes.…”