Schizophrenia is a common disorder with high heritability and a 10-fold increase in risk to siblings of probands. Replication has been inconsistent for reports of significant genetic linkage. To assess evidence for linkage across studies, rank-based genome scan meta-analysis (GSMA) was applied to data from 20 schizophrenia genome scans. Each marker for each scan was assigned to 1 of 120 30-cM bins, with the bins ranked by linkage scores (1 = most significant) and the ranks averaged across studies (R(avg)) and then weighted for sample size (N(sqrt)[affected casess]). A permutation test was used to compute the probability of observing, by chance, each bin's average rank (P(AvgRnk)) or of observing it for a bin with the same place (first, second, etc.) in the order of average ranks in each permutation (P(ord)). The GSMA produced significant genomewide evidence for linkage on chromosome 2q (PAvgRnk<.000417). Two aggregate criteria for linkage were also met (clusters of nominally significant P values that did not occur in 1,000 replicates of the entire data set with no linkage present): 12 consecutive bins with both P(AvgRnk) and P(ord)<.05, including regions of chromosomes 5q, 3p, 11q, 6p, 1q, 22q, 8p, 20q, and 14p, and 19 consecutive bins with P(ord)<.05, additionally including regions of chromosomes 16q, 18q, 10p, 15q, 6q, and 17q. There is greater consistency of linkage results across studies than has been previously recognized. The results suggest that some or all of these regions contain loci that increase susceptibility to schizophrenia in diverse populations.
Schizophrenia is thought to be a multifactorial disease with complex mode of inheritance. Using a two-stage strategy for another complex disorder, a number of putative IDDM-susceptibility genes have recently been mapped. We now report the results of a two-stage genome-wide search for genes conferring susceptibility to schizophrenia. In stage I, model-free linkage analyses of large pedigrees from Iceland, a geographical isolate, revealed 26 loci suggestive of linkage. In stage II, ten of these were followed-up in a second international collaborative study comprising families from Austria, Canada, Germany, Italy, Scotland, Sweden, Taiwan and the United States. Potential linkage findings of stage I on chromosomes 6p, 9 and 20 were observed again in the second sample. Furthermore, in a third sample from China, fine mapping of the 6p region by association studies also showed evidence for linkage or linkage disequilibrium. Combining our results with other recent findings revealed significant evidence for linkage to an area distal of the HLA region on chromosome 6p. However, in a fourth sample from Europe, the 6p fine mapping finding observed in the Chinese sample could not be replicated. Finally, evidence suggestive of locus heterogeneity and oligogenic transmission in schizophrenia was obtained.
Maturity-onset diabetes of the young (MODY) is a subgroup of diabetes which is inherited and which could account for 2±5 % of Type II diabetic patients [1]. Information on rare monogenic forms of diabetes could shed light on the development of the more common multigenic varieties of diabetes mellitus.Clinical and metabolic profiles of families with MODY can be diverse [2,3]. Currently, mutations in five genes are known to be associated with MODY and several families with MODY have not been linked to any of the known MODY genes [3±9]. Mutations in genes encoding transcription factors important for normal development and function of pancreatic beta cells have recently become a focus of attention in genetic studies of diabetes mellitus.The aim of this study was to investigate the clinical features and genetic causes of MODY in Iceland.
Subjects and methodsOver 85 % of known diabetic patients have attended the adult and paediatric diabetic clinics at Landspitali, University Hospital, Reykjavik [10,11]. The registers of these services were in-
Aging of rats results in slower activities of calcium transport by cardiac calcium adenosinetriphosphatase (ATPase) of the sarcoplasmic reticulum (SR) and mitochondrial cytochrome oxidase (COX). These enzyme activities are faster after exercise training of previously sedentary old rats. Our purpose was to determine whether the expression of the genes encoding SR calcium ATPase (SERCA2a) or COX is altered by exercise training. Old (24-mo-old) male Fischer 344 rats were assigned to SO (sedentary old) or EO (exercised old) groups and compared with younger (12-mo-old) sedentary rats (SM). EO rats were trained on a treadmill for 8-10 wk. SERCA2a and COX mRNAs were lower (P < 0.05) in SO compared with SM and EO, whereas glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and cardiac alpha-actin mRNAs were similar across groups. The immunoreactive protein contents of cardiac calcium ATPase, cytochrome c, sarcomeric actin, and GAPDH followed the changes, when observed, in mRNA contents. Thus pretranslational mechanisms may be modified in some genes during aging and exercise training of previously sedentary old rats.
The dramatic increase in the sales of antidepressants has not had any marked impact on the selected public health measures. Obviously, better treatment for depressive disorders is still needed in order to reduce the burden caused by them.
Through use of primary and secondary data sources for registration and validation, the incidence and prevalence of Type 1 (insulin-dependent) diabetes mellitus in children aged 0-14 years in Iceland has been completely ascertained for the years 1970-1989. The age-adjusted mean annual incidence per 100,000 for the 20-year period was 9.4 (95% confidence interval 7.8-11.3); similar for boys (9.9; 7.7-12.7) and girls (8.8; 6.7-11.5). Between 1970-1979 the incidence was 8.0 (6.0-10.6) and between 1980-1989 it was comparable at 10.8 (8.4-13.8) (p greater than 0.10). By Poisson regression analysis the variation in incidence was related to age at diagnosis (p less than 0.001), while a linear trend for calendar year at diagnosis did not reach statistical significance (p = 0.07). A quadratic curve, however, better described the temporal variation in incidence (p less than 0.05). The total prevalence per 1,000 by the end of 1979 and 1989 was similar, 0.45 (0.30-0.65) and 0.57 (0.40-0.79), respectively. In conclusion, this study confirms that both the incidence and prevalence of childhood Type 1 diabetes in Iceland are low compared to the other Nordic countries. The findings may suggest a causative role for environmental factors that are not related to latitude or ambient temperature.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.