Genkartierung in Isolatpopulationen

Isolated populations are important for mapping both monogenic and complex traits. We will discuss: 1. why isolated populations offer a unique opportunity for mapping projects; 2. the methods available and their selection; 3. the results accrued from isolated populations in mapping monogenic and complex traits thus far; 4. the conclusions that can be drawn for mapping studies in population isolates

Vulnerabilität und psychische Erkrankung

Vulnerability and psychic illness Based on a sample of 1701 college and university students from four different sites in Switzerland, the U.S., and Argentina, this study investigated the interrelationships between insufficient coping skills under chronic stress and impaired general health. We sought to develop standardised means for "early" identification of students at risk of mental health problems, as these students may benefit from "early" interventions before psychiatric symptoms develop and reach clinically relevant thresholds. All students completed two self-report questionnaires: the Coping Strategies Inventory "COPE" and the Zurich Health Questionnaire "ZHQ", with the latter assessing "regular exercises", "consumption behavior", "impaired physical health", "psychosomatic disturbances", and "impaired mental health". This data was subjected to structure analyses based on neural network approaches, using the different study sites' data subsets as independent "learning" and "test" samples. We found two highly stable COPE scales that quantified basic coping behaviour in terms of "activity-passivity" and "defeatism-resilience". The excellent reproducibility across study sites suggested that the new scales characterise socioculturally independent personality traits. Correlation analyses for external validation revealed a close relationship between high scores on the defeatism scale and impaired physical and mental health, hence underlining the scales' clinical relevance. Our results suggested in particular: (1.) the proposed method to be a powerful screening tool for early detection and prevention of psychiatric disorders; (2.) physical activity like regular exercises to play a critical role not only in preventing health problems but also in contributing to early intervention programs

Genetic vulnerability to atopy and asthma in ethnically diverse populations: analysis of a multinational sample

Using mite sensitization as endophenotype of atopy and asthma and family data from three European ethnicities (44 German, 26 Portuguese, and 19 British families with a total of 410 subjects) we searched for an oligogenic configuration of susceptibility loci that was equally valid for all three ethnicity-related samples. Our novel multilocus genotype-to-phenotype search strategy was based on a genetic similarity function that allowed us to quantify the inter-individual genetic distances d(xi, xj) between feature vectors xi, xj made up of the allelic genotype patterns of any two subjects i, j with respect to n loci l1, l 2, .. ln. Thus, we were able to quantify the between-population, the within-population, and the within-family genetic similarities. The question of ethnicity-independent susceptibility was addressed by treating the German families - ascertained from a population with intermediate prevalences of atopy and asthma - as "training" samples, while the British families - ascertained from a population with high prevalences of atopy and asthma - served as independent "test" samples, along with the Portuguese families who stemmed from a region with low prevalences of atopy and asthma. Relying upon the linkage paradigm, we evaluated the multilocus between-sib similarities which were expected to deviate from "0.5" in affected sib pairs if the region of interest contained markers close to disease-causing or protective genes. The reference value "0.5" was derived by determining the parent-offspring similarities which are always 0.5, irrespective of the affection status of parents and offspring. We found 11 vulnerability loci and 1 protective locus on chromosomes 2, 5, 6, 7, 8, 11, 12, 13, 15 and 19. These loci were reproducible across the ethnicities under comparison and constituted our ethnicity-independent oligogenic model of atopy and asthma susceptibility. Our results have cleared the way for systematic investigations into complex disorders, in particular psychiatric disorders, and to address the question of the extent to which genetic risk factors and their interactions constitute multigenic inheritance across populations and might constitute universal targets for treatment

Early Detection of the Risk of Developing Psychiatric Disorders: A Study of 461 Chinese University Students under Chronic Stress.

Chronic stress, a characteristic of modern time, has a significant impact on general health. In the context of psychiatric disorders, insufficient coping behavior under chronic stress has been linked to higher rates of (1) depressive symptoms among subjects of the general population, (2) relapse among patients under treatment for clinical depression, and (3) negative symptoms among subjects with an elevated vulnerability to psychosis. In this normative study we assessed basic coping behavior among 461 Chinese freshman university students along with their consumption behavior and general health in terms of regular exercises, physical health, psychosomatic disturbances, and mental health. The assessments relied on two instruments that have already demonstrated their capability of (1) reliably detecting insufficient coping behavior under chronic stress and (2) reliably quantifying the interrelation between coping behavior and mental health in the Western world. Thus, we aimed to complement existing data and to develop a generally available, socioculturally independent tool that can be used for the early detection of subjects with an elevated risk of mental health problems. Structural analyses yielded essentially the same scales "activity" and "defeatism" as previous studies on 2,500 students from Switzerland, Italy, Spain, the USA, and Argentina. These scales explained 74.3% of the observed variance in coping behavior among the 461 Chinese students. We found highly significant correlations (p < 0.0001) between the "defeatism" scale on the one hand, and the scales "regular use of medicine," "psychosomatic disturbances," and "impaired mental health" on the other. Particularly intriguing was the finding that a neural net classifier could be constructed to identify students with the highest contributions to the interrelation between "coping behavior" and "mental health," yielding a correlation coefficient as high as r = 0.597 for the respective subgroup. Based on the normative data, an online tool for risk assessments was developed with immediate feedback to users. This study provided another piece of evidence regarding the close link between basic coping behavior and mental health, across cultures and ethnicities. In consequence, our approach to quantifying basic coping behavior, along with other risk factors, can be expected to clear the way for an "early" detection of students with an elevated risk of stress-related mental health problems, nota bene prior to the development of clinically relevant symptoms. The socioeconomic impact of the potential prevention of depressive -disorders, and psychiatric disorders in general, may be enormous

A genome-wide screen on the genetics of atopy in a multiethnic European population reveals a major atopy locus on chromosome 3q21.3

BACKGROUND: Dissecting complex diseases in underlying distinct traits and studying these for their genetic basis might enhance the power as well as the specificity, of detection of disease genes. These phenotypes are known as intermediate phenotypes. OBJECTIVE: We were interested in the atopic basis of asthma, and used the sensitization to mite (Dermatophagoides pteronyssinus) allergens as a pathophysiologically important intermediate phenotype. METHODS: This time we performed a genome-wide scan based on the same already used multiethnic European population consisting of 82 nuclear families with at least two affected siblings. We carried out nonparametric as well as parametric MOD-score analyses based on the genotypes of 603 microsatellite markers. RESULTS: In comparison with our first genome-wide candidate region search three novel regions additionally appeared to be significant. We obtained significant results for the region 2p12 with a MOD score of 3.35 and for the region 16q21 with a MOD score of 4.18. The most significant result was found for the region 3q21.3 with the same microsatellite marker, which showed significant linkage to atopic dermatitis (AD) in another study with a MOD score of 4.51 and an nonparametric linkage analysis (NPL) of 4.00. CONCLUSION: Our findings indicate that atopy, allergic asthma, allergic rhinitis and AD on the one hand are distinct traits on both the clinical and genetic basis, but on the other hand, our results also underline that these traits are closely related diseases concerning the atopic basis of the traits

Gemeindenahe psychiatrische Akutbehandlung in Gastfamilien. Kostengünstige Alternative zum Klinikaufenthalt bei hoher Patientenzufriedenheit

BACKGROUND: Over recent decades, institutional psychiatric care has shifted its focus from traditional inpatient treatment to a variety of more advanced outpatient services. Within this context, a new "crisis home" programme (CHP) was launched in Zurich on 1 January 2005. With this programme, mentally ill patients can avoid hospitalization by living with a host family for a certain time period while receiving standard outpatient care. In this study we addressed the question of whether the quite substantial financial advantages of the Zurich CHP over traditional inpatient care are achieved at the expense of a reduced quality of care. SAMPLE AND METHODS: Between 1 January 2005 and 30 June 2007, a total of 33 patients enrolled in the Zurich CHP with an average stay of 19 days at host families. The vast majority of the patients (85%) were moderately to severely ill at study entry. Of these patients data were collected in a standardized way on the basis of five rating instruments. The statistical data analysis included cross-comparisons with corresponding inpatient data. RESULTS: Results showed that (1) the CHP works well in a routine setting and provides cost-efficient interventions for patients in acute crises; (2) the financial advantages of the Zurich host family programme over traditional inpatient care do not lead to a reduced quality in patient care; (3) patients suffering from severe mental illnesses clearly benefit from this programme, thus avoiding hospitalization. CONCLUSIONS: The Zurich CHP is a cost-efficient alternative to traditional inpatient treatment. Specifically, our results suggest that this type of acute crisis intervention should be established as a standard psychiatric care service

A novel locus for arterial hypertension on chromosome 1p36 maps to a metabolic syndrome trait cluster in the Sorbs, a Slavic population isolate in Germany

OBJECTIVE: Genome-wide linkage studies and genome-wide association studies have not as yet identified major genes contributing to primary hypertension in the general population. This state-of-affairs suggests considerable heterogeneity with small contributing effects for primary hypertension, or other complex genetic traits, in outbred populations. Isolated populations, as recent data from Iceland and French Canada suggest, could offer a solution to this problem. METHODS: We studied a Slavic isolate in Germany, the Sorbs, and genotyped 1040 polymorphic microsatellite markers in 87 multigeneration families. RESULTS: Our genome-wide linkage scan revealed a locus on chromosome 1p36.13 at D1S3669-D1S2826 (40.95 cM Marshfield coordinates; logarithm of the odds = 3.45, nominal P = 0.00003) that reached genome-wide significance (P = 0.004), indicating the increased power in isolated populations. The chromosome 1 locus maps to a region in which traits such as diabetes, hyperlipidemia, obesity and BMI cluster. CONCLUSION: Our results suggest that this locus contributes to the metabolic syndrome, and that further attention in this and other populations is warranted