Patrick and Susan Matthiesen playing chess at Aenny Catzenstein nee Gottschalk's 80th birthday; London Portraits Family

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Family and guests at Aenny Catzenstein nee Gottschalk's 80th birthday; London.

Front row l-r: Beatrice Durand, Francine Durand and Aenny Catzenstein, the boys are Ara-Serge Donabedian and Patrick Matthiesen and the adults are Susan Prior, Francis Matthiesen, Maren Matthiesen, Nino Fabri and Olga Matthiesen,

Genome-wide linkage analysis of multiple measures of neuroticism of 2 large cohorts from Australia and the Netherlands

CONTEXT People meeting diagnostic criteria for anxiety or depressive disorders tend to score high on the personality scale of neuroticism. Studying this personality dimension can give insights into the etiology of these important psychiatric disorders. OBJECTIVES To undertake a comprehensive genome-wide linkage study of neuroticism using large study samples that have been measured multiple times and to compare the results between countries for replication and across time within countries for consistency. DESIGN Genome-wide linkage scan. SETTING Twin individuals and their family members from Australia and the Netherlands. PARTICIPANTS Nineteen thousand six hundred thirty-five sibling pairs completed self-report questionnaires for neuroticism up to 5 times over a period of up to 22 years. Five thousand sixty-nine sibling pairs were genotyped with microsatellite markers. METHODS Nonparametric linkage analyses were conducted in MERLIN-REGRESS for the mean neuroticism scores averaged across time. Additional analyses were conducted for the time-specific measures of neuroticism from each country to investigate consistency of linkage results. RESULTS Three chromosomal regions exceeded empirically derived thresholds for suggestive linkage using mean neuroticism scores: 10p 5 Kosambi cM (cM) (Dutch study sample), 14q 103 cM (Dutch study sample), and 18q 117 cM (combined Australian and Dutch study sample), but only 14q retained significance after correction for multiple testing. These regions all showed evidence for linkage in individual time-specific measures of neuroticism and 1 (18q) showed some evidence for replication between countries. Linkage intervals for these regions all overlap with regions identified in other studies of neuroticism or related traits and/or in studies of anxiety in mice. CONCLUSIONS Our results demonstrate the value of the availability of multiple measures over time and add to the optimism reported in recent reviews for replication of linkage regions for neuroticism. These regions are likely to harbor causal variants for neuroticism and its related psychiatric disorders and can inform prioritization of results from genome-wide association studies.

Family and guests at Aenny Catzenstein nee Gottschalk's 80th birthday party; London.

Dinner scene with Franz Mattheisen left, daughter Susan Mattheisen next to him, next daughter Maren Matthiesen, his wife Olga Matthiesen at the end of the table. Beatrice Durand is facing the camera

Gottschalk family on vacation; Norderney, Germany.

Left to right: two unidentified women, Kurt Gottschalk, Therese Gottschalk nee Molling, Fritz Gottschalk, unidentified woman (the maid?), and Elizabeth Gottschalk

Gottschalk family on vacation in front of Kurhaus Brunig; Norderney, Germany.

From left to right: man with camera: Karl Gottschalk; sitting on stairs: Fritz Gottschalk, unidentified woman, Therese Gottschalk nee Molling, Hans Ludwig, Kurt Gottschalk, unidentified woman (maid?) and Elizabeth Gottschalk

Family of Dr. Max and Helen Bejach portraits family

unidentified family members

Consistently replicating locus linked to migraine on 10q22-q23

Here, we present the results of two genome-wide scans in two diverse populations in which a consistent use of recently introduced migraine-phenotyping methods detects and replicates a locus on 10q22-q23, with an additional independent replication. No genetic variants have been convincingly established in migraine, and although several loci have been reported, none of them has been consistently replicated. We employed the three known migraine-phenotyping methods (clinical end diagnosis, latent-class analysis, and trait-component analysis) with robust multiple testing correction in a large sample set of 1675 individuals from 210 migraine families from Finland and Australia. Genome-wide multipoint linkage analysis that used the Kong and Cox exponential model in Finns detected a locus on 10q22-q23 with highly significant evidence of linkage (LOD 7.68 at 103 cM in female-specific analysis). The Australian sample showed a LOD score of 3.50 at the same locus (100 cM), as did the independent Finnish replication study (LOD score 2.41, at 102 cM). In addition, four previously reported loci on 8q21, 14q21, 18q12, and Xp21 were also replicated. A shared-segment analysis of 10q22-q23 linked Finnish families identified a 1.6-9.5 cM segment, centered on 101 cM, which shows in-family homology in 95% of affected Finns. This region was further studied with 1323 SNPs. Although no significant association was observed, four regions warranting follow-up studies were identified. These results support the use of symptomology-based phenotyping in migraine and suggest that the 10q22-q23 locus probably contains one or more migraine susceptibility variants.

Lola and George Gruenthal in Neu-Ulm Portraits Family

"When will you come back?" (written in German on verso)