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- Lewis, Cathryn M, et al.
(author)
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Genome scan meta-analysis of schizophrenia and bipolar disorder, part II : Schizophrenia
- 2003
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In: American Journal of Human Genetics. - 0002-9297 .- 1537-6605. ; 73:1, s. 34-48
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Journal article (peer-reviewed)abstract
- 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.
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| 4. |
- Rehm, J., et al.
(author)
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Alcohol
- 2004
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In: Comparative quantification of health risks. - Geneva : World Health Organization. - 9241580313 ; , s. 959-1108
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Book chapter (other academic/artistic)
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| 5. |
- Rehm, J., et al.
(author)
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Alcohol as a risk factor for global burden of disease
- 2003
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In: European Addiction Research. - : S. Karger AG. - 1022-6877 .- 1421-9891. ; 9:4, s. 157-164
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Journal article (peer-reviewed)abstract
- AIM:To make quantitative estimates of the burden of disease attributable to alcohol in the year 2000 on a global basis.DESIGN:Secondary data analysis.MEASUREMENTS:Two dimensions of alcohol exposure were included: average volume of alcohol consumption and patterns of drinking. There were also two main outcome measures: mortality, i.e. the number of deaths, and disability-adjusted life years (DALYs), i.e. the number of years of life lost to premature mortality or to disability. All estimates were prepared separately by sex, age group and WHO region.FINDINGS:Alcohol causes a considerable disease burden: 3.2% of the global deaths and 4.0% of the global DALYs in the year 2000 could be attributed to this exposure. There were marked differences by sex and region for both outcomes. In addition, there were differences by disease category and type of outcome; in particular, unintentional injuries contributed most to alcohol-attributable mortality burden while neuropsychiatric diseases contributed most to alcohol-attributable disease burden.DISCUSSION/CONCLUSIONS:The underlying assumptions are discussed and reasons are given as to why the estimates should still be considered conservative despite the considerable burden attributable to alcohol globally.
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| 6. |
- Rehm, J., et al.
(author)
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The relationship of average volume of alcohol consumption and patterns of drinking to burden of disease : an overview
- 2003
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In: Addiction. - : Wiley. - 0965-2140 .- 1360-0443. ; 98:9, s. 1209-1228
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Research review (peer-reviewed)abstract
- Aims As part of a larger study to estimate the global burden of disease attributable to alcohol:• to quantify the relationships between average volume of alcohol consumption, patterns of drinking and disease and injury outcomes, and• to combine exposure and risk estimates to determine regional and global alcohol-attributable fractions (AAFs) for major disease and injury categories.Design, methods, setting Systematic literature reviews were used to select diseases related to alcohol consumption. Meta-analyses of the relationship between alcohol consumption and disease and multi-level analyses of aggregate data to fill alcohol–disease relationships not currently covered by individual-level data were used to determine the risk relationships between alcohol and disease. AAFs were estimated as a function of prevalence of exposure and relative risk, or from combining the aggregate multi-level analyses with prevalence data.Findings Average volume of alcohol consumption was found to increase risk for the following major chronic diseases: mouth and oropharyngeal cancer; oesophageal cancer; liver cancer; breast cancer; unipolar major depression; epilepsy; alcohol use disorders; hypertensive disease; hemorrhagic stroke; and cirrhosis of the liver. Coronary heart disease (CHD), unintentional and intentional injuries were found to depend on patterns of drinking in addition to average volume of alcohol consumption. Most effects of alcohol on disease were detrimental, but for certain patterns of drinking, a beneficial influence on CHD, stroke and diabetes mellitus was observed.Conclusions Alcohol is related to many major disease outcomes, mainly in a detrimental fashion. While average volume of consumption was related to all disease and injury categories under consideration, pattern of drinking was found to be an additional influencing factor for CHD and injury. The influence of patterns of drinking may be underestimated because pattern measures have not been included in many epidemiologic studies. Generalizability of the results is limited by methodological problems of the underlying studies used in the present analyses. Future studies need to address these methodological issues in order to obtain more accurate risk estimates.
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