Chromosome 6p is one of the most commonly implicated regions in the genome-wide linkage scans of schizophrenia, whereas further association studies for markers in this region were inconsistent likely due to heterogeneity. This study aimed to identify more homogeneous subgroups of families for fine mapping on regions around markers D6S296 and D6S309 (both in 6p24.3) as well as D6S274 (in 6p22.3) by means of similarity in neurocognitive functioning. A total of 160 families of patients with schizophrenia comprising at least two affected siblings who had data for 8 neurocognitive test variables of the Continuous Performance Test (CPT) and the Wisconsin Card Sorting Test (WCST) were subjected to cluster analysis with data visualization using the test scores of both affected siblings. Family clusters derived were then used separately in family-based association tests for 64 single nucleotide polymorphisms covering the region of 6p24.3 and 6p22.3. Three clusters were derived from the family-based clustering, with deficit cluster 1 representing deficit on the CPT, deficit cluster 2 representing deficit on both the CPT and the WCST, and a third cluster of non-deficit. After adjustment using false discovery rate for multiple testing, SNP rs13873 and haplotype rs1225934-rs13873 on BMP6-TXNDC5 genes were significantly associated with schizophrenia for the deficit cluster 1 but not for the deficit cluster 2 or non-deficit cluster. Our results provide further evidence that the BMP6-TXNDC5 locus on 6p24.3 may play a role in the selective impairments on sustained attention of schizophrenia.
[1] The objective of this paper is to describe a statistical downscaling model based on established links between large scale variables from a general circulation model (GCM) and regional rainfall to project climate change over East Asia in the 21st century. We develop a SVD (singular value decomposition)-based regression model to downscale the GCM data. In order to establish a link between monthly regional precipitation and large scale variable (mean sea level pressure, 10 m wind speed, or 2 m temperature), we used the IS92a scenario data of ECHAM4/OPCY3 and the data from the Climate Research Unit from 1901 to 1990. In the 20th century, their connections have remained unchanged over time for all seasons. The continuity of these relationships to the next century is tested by checking the similarity in the main SVD modes of predictors and the empirical orthogonal functions of predictors throughout the 20th and 21st century. Furthermore, comparing the SVD-downscaled and ECHAM4-projected changes of precipitation in the 2090s with respect to the 1990s reveals similar patterns over most areas with much more detailed regional characteristics, although the magnitude of change is not compatible. In all, the annual rainfall over East Asia is projected to increase over northern China and the Indochina peninsula and to decrease over the coast of southern China by the end of the 21st century.
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