Background Most studies that have evaluated the association between the body-mass index (BMI) and the risks of death from any cause and from specific causes have been conducted in populations of European origin. Methods We performed pooled analyses to evaluate the association between BMI and the risk of death among more than 1.1 million persons recruited in 19 cohorts in Asia. The analyses included approximately 120,700 deaths that occurred during a mean follow-up period of 9.2 years. Cox regression models were used to adjust for confounding factors. Results In the cohorts of East Asians, including Chinese, Japanese, and Koreans, the lowest risk of death was seen among persons with a BMI (the weight in kilograms divided by the square of the height in meters) in the range of 22.6 to 27.5. The risk was elevated among persons with BMI levels either higher or lower than that range — by a factor of up to 1.5 among those with a BMI of more than 35.0 and by a factor of 2.8 among those with a BMI of 15.0 or less. A similar U-shaped association was seen between BMI and the risks of death from cancer, from cardiovascular diseases, and from other causes. In the cohorts comprising Indians and Bangladeshis, the risks of death from any cause and from causes other than cancer or cardiovascular disease were increased among persons with a BMI of 20.0 or less, as compared with those with a BMI of 22.6 to 25.0, whereas there was no excess risk of either death from any cause or cause-specific death associated with a high BMI. Conclusions Underweight was associated with a substantially increased risk of death in all Asian populations. The excess risk of death associated with a high BMI, however, was seen among East Asians but not among Indians and Bangladeshis.

In an analysis of 31,717 cancer cases and 26,136 cancer-free controls drawn from 13 genome-wide association studies (GWAS), we observed large chromosomal abnormalities in a subset of clones from DNA obtained from blood or buccal samples. Mosaic chromosomal abnormalities, either aneuploidy or copy-neutral loss of heterozygosity, of size >2 Mb were observed in autosomes of 517 individuals (0.89%) with abnormal cell proportions between 7% and 95%. In cancer-free individuals, the frequency increased with age; 0.23% under 50 and 1.91% between 75 and 79 (p=4.8×10−8). Mosaic abnormalities were more frequent in individuals with solid-tumors (0.97% versus 0.74% in cancer-free individuals, OR=1.25, p=0.016), with a stronger association for cases who had DNA collected prior to diagnosis or treatment (OR=1.45, p=0.0005). Detectable clonal mosaicism was common in individuals for whom DNA was collected at least one year prior to diagnosis of leukemia compared to cancer-free individuals (OR=35.4, p=3.8×10−11). These findings underscore the importance of the role and time-dependent nature of somatic events in the etiology of cancer and other late-onset diseases.

We conducted a genome-wide association study of gastric cancer (GC) and esophageal squamous cell carcinoma (ESCC) in ethnic Chinese subjects in which we genotyped 551,152 single nucleotide polymorphisms (SNPs). We report a combined analysis of 2,240 GC cases, 2,115 ESCC cases, and 3,302 controls drawn from five studies. In logistic regression models adjusted for age, sex, and study, multiple variants at 10q23 had genome-wide significance for GC and ESCC independently. A notable signal was rs2274223, a nonsynonymous SNP located in PLCE1, for GC (P=8.40×10−9; per allele odds ratio (OR) = 1.31) and ESCC (P=3.85×10−9; OR = 1.34). The association with GC differed by anatomic subsite. For tumors located in the cardia the association was stronger (P=4.19 × 10−15; OR= 1.57) and for those located in the noncardia stomach it was absent (P=0.44; OR=1.05). Our findings at 10q23 could provide insight into the high incidence rates of both cancers in China.

OsbZIP23 is a member of the basic leucine zipper (bZIP) transcription factor family in rice (Oryza sativa). Expression of OsbZIP23 is strongly induced by a wide spectrum of stresses, including drought, salt, abscisic acid (ABA), and polyethylene glycol treatments, while other stress-responsive genes of this family are slightly induced only by one or two of the stresses. Transactivation assay in yeast demonstrated that OsbZIP23 functions as a transcriptional activator, and the sequences at the N terminus (amino acids 1-59) and a region close to the C terminus (amino acids 210-240) are required for the transactivation activity. Transient expression of OsbZIP23-green fluorescent protein in onion (Allium cepa) cells revealed a nuclear localization of the protein. Transgenic rice overexpressing OsbZIP23 showed significantly improved tolerance to drought and high-salinity stresses and sensitivity to ABA. On the other hand, a null mutant of this gene showed significantly decreased sensitivity to a high concentration of ABA and decreased tolerance to high-salinity and drought stress, and this phenotype can be complemented by transforming the OsbZIP23 back into the mutant. GeneChip and real-time polymerase chain reaction analyses revealed that hundreds of genes were up-or down-regulated in the rice plants overexpressing OsbZIP23. More than half of these genes have been annotated or evidenced for their diverse functions in stress response or tolerance. In addition, more than 30 genes that are possible OsbZIP23-specific target genes were identified based on the comparison of the expression profiles in the overexpressor and the mutant of OsbZIP23. Collectively, these results indicate that OsbZIP23 functions as a transcriptional regulator that can regulate the expression of a wide spectrum of stress-related genes in response to abiotic stresses through an ABA-dependent regulation pathway. We propose that OsbZIP23 is a major player of the bZIP family in rice for conferring ABA-dependent drought and salinity tolerance and has high potential usefulness in genetic improvement of stress tolerance.

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