Large-Scale Whole-Genome Sequencing of Three Diverse Asian Populations in Singapore.

Underrepresentation of Asian genomes has hindered population and medical genetics research on Asians, leading to population disparities in precision medicine. By whole-genome sequencing of 4,810 Singapore Chinese, Malays, and Indians, we found 98.3 million SNPs and small insertions or deletions, over half of which are novel. Population structure analysis demonstrated great representation of Asian genetic diversity by three ethnicities in Singapore and revealed a Malay-related novel ancestry component. Furthermore, demographic inference suggested that Malays split from Chinese ∼24,800 years ago and experienced significant admixture with East Asians ∼1,700 years ago, coinciding with the Austronesian expansion. Additionally, we identified 20 candidate loci for natural selection, 14 of which harbored robust associations with complex traits and diseases. Finally, we show that our data can substantially improve genotype imputation in diverse Asian and Oceanian populations. These results highlight the value of our data as a resource to empower human genetics discovery across broad geographic regions.

Exploring Adaptive Phenotypes for the Human Calcium-Sensing Receptor Polymorphism R990G.

Rainforest hunter-gatherers from Southeast Asia are characterized by specific morphological features including a particularly dark skin color (D), short stature (S), woolly hair (W), and the presence of steatopygia (S)-fat accumulation localized in the hips (DSWS phenotype). Based on previous evidence in the Andamanese population, we first characterized signatures of adaptive natural selection around the calcium-sensing receptor gene in Southeast Asian rainforest groups presenting the DSWS phenotype and identified the R990G substitution (rs1042636) as a putative adaptive variant for experimental follow-up. Although the calcium-sensing receptor has a critical role in calcium homeostasis by directly regulating the parathyroid hormone secretion, it is expressed in different tissues and has been described to be involved in many biological functions. Previous works have also characterized the R990G substitution as an activating polymorphism of the calcium-sensing receptor associated with hypocalcemia. Therefore, we generated a knock-in mouse for this substitution and investigated organismal phenotypes that could have become adaptive in rainforest hunter-gatherers from Southeast Asia. Interestingly, we found that mouse homozygous for the derived allele show not only lower serum calcium concentration but also greater body weight and fat accumulation, probably because of enhanced preadipocyte differentiation and lipolysis impairment resulting from the calcium-sensing receptor activation mediated by R990G. We speculate that such differential features in humans could have facilitated the survival of hunter-gatherer groups during periods of nutritional stress in the challenging conditions of the Southeast Asian tropical rainforests.

Genome-wide association study on meningioma risk in Japan: a multicenter prospective study.

PURPOSE: Although meningiomas are the most common primary intracranial tumors, their genetic etiologies have not been fully elucidated. To date, only two genome-wide association studies (GWASs) have focused on European ancestries, despite ethnic differences in the incidence of meningiomas. The aim of this study was to conduct the first GWAS of Japanese patients with meningiomas to identify the SNPs associated with meningioma susceptibility. METHODS: In this multicenter prospective case-control study, we studied 401 Japanese patients with meningioma admitted in five institutions in Japan, and 50,876 control participants of Japanese ancestry enrolled in Biobank Japan. RESULTS: The quality control process yielded 536,319 variants and imputation resulted in 8,224,735 variants on the autosomes and 224,820 variants on the X chromosomes. This GWAS eventually revealed no genetic variants with genome-wide significance (P < 5 × 10 - 8) and observed no significant association in the previously reported risk variants rs11012732 and rs2686876 due to low minor allele frequency in the Japanese population. CONCLUSION: This is the first GWAS of meningiomas in East Asian populations and is expected to contribute to the development of GWAS research for meningiomas.

Impact of Cachexia on Chemotherapy Efficacy and Survival in Pancreatic Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND AND OBJECTIVE: Pancreatic cancer (PC) is a significant cause of cancer-related mortality, with limited curative options and high rates of cachexia, a debilitating syndrome associated with poor prognosis. While previous research has linked sarcopenia to poor outcomes in PC, the correlation between cachexia and treatment outcomes remains underexplored. This meta-analysis aims to investigate the association between cachexia and overall survival and time to treatment failure in advanced PC patients undergoing first-line chemotherapy. METHOD: A systematic search of electronic databases was conducted following PRISMA guidelines. Eligible studies compared cachexic and non-cachexic PC patients, reporting outcomes of observed survival or time to treatment failure. Data extraction and analysis were performed using Comprehensive Meta-Analysis Version 3.3, employing random-effects models and sensitivity analyses to assess heterogeneity and bias. RESULTS: Seven observational studies involving 2834 PC patients were included. The incidence of cachexia was 45% (95% CI: 0.27-0.65), with a higher prevalence in East Asian populations. Cachexic patients experienced significantly earlier treatment failure (SDM: -2.22, 95% CI: -2.6 to -1.7, P = 0.0001) and higher mortality risk (HR: 2.02, 95% CI: 1.17-3.48, P = 0.011) compared to non-cachexic patients. Overall survival was lower in cachexic patients (SDM: -2.34, 95% CI: -3.7 to -0.90, P = 0.001), with considerable heterogeneity across studies. Meta-regression analysis revealed significant differences between countries but insignificant correlations with age. CONCLUSION: Cachexia is associated with reduced overall survival, early chemotherapy failure, and elevated mortality in advanced PC patients undergoing first-line chemotherapy. Recognition and management of cachexia are crucial for optimizing treatment outcomes and improving patient survival. Future research should focus on prospective studies to better understand the impact of cachexia on treatment response and develop tailored interventions to mitigate its adverse effects.

Pancreatic cancer (PC) presents a formidable challenge due to its limited treatment options and association with cachexia, a debilitating condition linked to poor prognosis. This meta-analysis investigates the relationship between cachexia and treatment outcomes in advanced PC patients undergoing first-line chemotherapy. Seven observational studies encompassing 2834 patients were analyzed, revealing a 45% incidence of cachexia, notably higher in East Asian populations. Cachexic patients exhibited earlier treatment failure and higher mortality risk compared to non-cachexic counterparts. Their overall survival was significantly reduced, although with notable heterogeneity across studies. Meta-regression analysis highlighted variations between countries but found no significant correlation with age. The findings underscore the importance of recognizing and addressing cachexia to optimize treatment outcomes and enhance patient survival. Future research should emphasize prospective studies to further elucidate cachexia's impact on treatment response and develop tailored interventions to alleviate its adverse effects.

Association of Valve Size and Hemodynamic Performance With Clinical Outcomes in Aortic Valve Replacement　- A Long-Term Follow-up in an Asian Population.

BACKGROUND: Studies of the influence of smaller body type on the severity of prosthesis-patient mismatch (PPM) after small-sized surgical aortic valve replacement (SAVR) are few, but the issue is particularly relevant for Asian patients.Methods and Results: 695 patients who underwent SAVR with bioprosthetic valves had their hemodynamic valve performance analyzed at 3 months, 1 year, 3 years, and 5 years after operation, and clinical outcomes were assessed. The patients were stratified into 3 valve size groups: 19/21, 23, and 25/27 mm. A smaller valve was associated with higher mean pressure gradients at the 4 time points after operation (P trend <0.05). However, the 3 valve size groups demonstrated no significant differences in the risk of clinical events. At none of the time points did patients with projected PPM show increased mean pressure gradients (P>0.05), whereas patients with measured PPM did (P<0.05). Compared with patients with projected PPM, those with measured PPM demonstrated higher rates of infective endocarditis readmission (adjusted hazard ratio [aHR] 3.31, 95% confidence interval [CI] 1.06-10.39) and a higher risk of composite outcomes (aHR 1.45, 95% CI 0.95-2.22, P=0.087). CONCLUSIONS: Relative to those receiving larger valves, patients receiving small bioprosthetic valves had poorer hemodynamic performance but did not demonstrate differences in clinical events in long-term follow-up.

Performance evaluation of an in-house panel containing 59 autosomal InDels for forensic identification in Chinese Hui and Mongolian groups.

In recent years, a novel multiplex system containing two mini-short tandem repeats, 59 autosomal InDels, two Y-chromosomal InDels, and the Amelogenin gene with all amplicons less than 200 bp has been constructed and validated by ourselves for forensic degration sample, and its forensic application efficiency has been studied in Chinese some populations. Herein, the population genetic polymorphisms of these loci were investigated in Chinese Hui (n = 249) and Mongolian (n = 222) ethnic groups using direct multiplex amplification and capillary electrophoresis platform. The forensic identification efficiencies of this self-developed system were further evaluated in these two groups. And the results showed that the values of the combined power of discrimination were 0.9999999999999999999999999999006 (Hui) and 0.999999999999999999999999999738 (Mongolian), respectively. Moreover, the combined power of exclusion values were 0.99999817 (Hui) and 0.99999779 (Mongolian). The 59 autosomal InDels used in this study exhibited high forensic identification efficiencies in 10 East Asian populations, which was also expected to be a new powerful tool for identifying degraded biological materials in East Asian populations.

Tea Consumption and Gut Microbiome in Older Chinese Adults.

BACKGROUND: Animal and small-cohort human studies have shown that tea consumption affects the gut microbiome, but evidence from large cohort studies is lacking. OBJECTIVES: We examined associations between tea consumption and gut microbiome composition among older Chinese adults. METHODS: The study included 1179 men and 1078 women from the Shanghai Men's and Women's Health Studies, who reported tea drinking status, type, amount, and duration at baseline and follow-up surveys (1996-2017) and were free of cancer, cardiovascular disease, and diabetes at stool collection (2015-2018). Fecal microbiome was profiled using 16S rRNA sequencing. Associations of tea variables with microbiome diversity and taxa abundance were evaluated using linear or negative binomial hurdle models after adjusting for sociodemographics, lifestyle, and hypertension status. RESULTS: Mean age at stool collection was 67.2 ± 9.0 y in men and 69.6 ± 8.5 y in women. Tea drinking was not associated with microbiome ɑ-diversity in men or women; however, all tea variables were associated with ß-diversity in men (P < 0.001). Significant associations with taxa abundance were also observed mostly in men. Current tea drinking, mainly green tea drinking, was associated with increase in orders Synergistales and RF39 in men (ß = 0.30 to 0.42, all PFDR ≤ 0.10) but not in women (PInteraction-sex = 0.01). Also, increase in families Coriobacteriaceae, Odoribacteraceae, genera Collinsella, Odoribacter, and species Collinsella aerofaciens, Coprococcus catus, and Dorea formicigenerans were observed among men who drank >3.3 cups (781 mL)/d compared to that of nondrinkers (all PFDR <0.10). The increased Coprococcus catus related to tea drinking was more evident among men without hypertension and inversely associated with the prevalence of hypertension (OR: 0.90; 95% CI: 0.84, 0.97; PFDR = 0.03). CONCLUSIONS: Tea consumption may affect gut microbiome ß-diversity and abundance of some bacteria, which may contribute to reduced hypertension risk in Chinese men. Future studies should examine the sex-specific tea-gut microbiome associations and how certain bacteria may mediate the health benefits of tea.

Alcohol increases treatment failure for Helicobacter pylori eradication in Asian populations.

BACKGROUND AND AIM: Whether alcohol intake is associated with Helicobacter pylori (H. pylori) eradication failure remains controversial, and this meta-analysis was aimed at investigating the effect of alcohol on the risk of H. pylori eradication failure. METHODS: Relevant studies were systematically screened for and retrieved from PubMed and Web of Science (updated to January 2022), and relevant references were manually reviewed. The odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Subgroup, publication bias, and sensitivity analyses were also conducted. RESULTS: A total of 40 studies were included in the meta-analysis. No significant association was found between alcohol consumption and the risk of H. pylori eradication failure (OR = 1.09, 95% CI, 0.94-1.26). However, in subgroup analyses stratified by region, a positive association was found in Asian patients (OR = 1.23, 95% CI, 1.03-1.47). In Asian patients, alcohol consumption was associated with the risk of H. pylori eradication failure when the duration of therapy was > 7 days (OR = 1.17, 95% CI, 1.10-1.25), when the treatment regimen included nitroimidazoles (OR = 1.16, 95% CI, 1.09-1.24), and when patients were treated with bismuth-containing quadruple therapy (OR = 1.17, 95% CI, 1.10-1.25). Alcohol intake > 40 g/day was associated with H. pylori eradication failure (OR = 3.17, 95% CI, 1.56-6.41). Moreover, in Asian patients who were administered a vonoprazan (VPZ)-based therapy regimen, alcohol consumption had no effect on H. pylori eradication rates (OR = 1.73, 95% CI, 0.98-3.05). CONCLUSION: Our meta-analysis clearly showed that a higher daily alcohol intake was associated with a higher risk of H. pylori eradication failure in Asian populations. Moreover, a VPZ-based treatment regimen can prevent this effect.

A high-performance SNP panel developed by machine-learning approaches for characterizing genetic differences of Southern and Northern Han Chinese, Korean, and Japanese individuals.

Population stratification analyses targeting genetically closely related East Asians have revealed that distinguishable differentiation exists between Han Chinese, Korean, and Japanese individuals, as well as between southern (S-) and northern (N-) Han Chinese. Previous studies offer a number of choices for ancestry informative single nucleotide polymorphisms (AISNPs) to discriminate East-Asian populations. In this study, we collected and examined the efficiency of 1185 AISNPs using frequency and genotype data from various publicly available databases. With the aim to perform fine-scale classification of S-Han, N-Han, Korean, and Japanese subjects, machine-learning methods (Softmax and Random Forest) were used to screen a panel of highly informative AISNPs and to develop a superior classification model. Stepwise classification was implemented to increase and balance the discrimination in the process of AISNP selection, first discriminating Han, Korean, and Japanese individuals, and then characterizing stratification between S-Han and N-Han. The final 272-AISNP panel is an alternative optimization of various previous works, which promises reliable and >90% accuracy in classification of the four East-Asian groups. This AISNP panel and the machine-learning model could be a useful and superior choice in medical genome-wide association studies and in forensic investigations for unknown suspect identity.

Racism and the mental health of East Asian diasporas in North America: a scoping review.

BACKGROUND: The COVID-19 pandemic heightened anti-Asian racism towards East Asian diasporas in North America. Experiences of racism encountered by East Asian communities have been documented to negatively impact their mental health. METHODS: A scoping review was undertaken following Arksey and O'Malley's (2005) methodology to (a) map the foci of literature on racism and the mental health of East Asian diasporas in North America and (b) identify gaps in the current literature. RESULTS: A total of 1309 articles were identified in May 2021. Based on the inclusion criteria, 35 records were included. Two distinct mental health foci were found: mental health outcomes and mental healthcare access and utilization. The majority (n = 22) of the articles focused on racism at the interpersonal level. Six articles provided anti-racism solutions at the individual level, such as overcoming biases. Five articles targeted anti-racism solutions from both the individual and institutional levels, while 1 article addressed barriers at the institutional level, such as dismantling sanctioned power hierarchies. CONCLUSION: The expanding knowledge base on COVID-19-related racial discrimination is reminiscent of previous literature examining the history of anti-Asian racism in North America. Greater attention is needed to navigate impactful anti-racism solutions for East Asian populations' mental health in North America.

A targeted ancestry informative InDels panel on capillary electrophoresis for ancestry inference in Asian populations.

CE is the primary methodology used in forensic DNA typing. Alleles of commonly used types of genetic markers could be separated and detected via CE based on dye color and migration time. Insertion/deletion (InDel) is an ideal genetic marker for forensic DNA analysis due to their abundance in the human genome, low mutation rate, availability of their allele types via CE, and elimination of stutter peaks. Moreover, InDels could be used as ancestry informative markers since allele frequencies of InDels is different among geographically separated populations. Several ancestry informative insertion/deletion panels have been established based on CE platform to achieve the intercontinental populations distinction. However, improvements to differentiate intracontinental populations is few. In this study, 21 InDels with fixation index (FST ) > 0.15 were selected and assembled into one ancestry informative insertion/deletion panel. Using well-designed primers, those 21 InDels could be amplified successfully and genotyped on the CE platform accurately and completely. The panel showed a large FST distance distinction among the ten Asian populations. Using clustering analysis, ten Asian populations were classified into three subgroups: East Asian, Southeast Asian, and South Asian subgroups. To evaluate the panel's capability in ancestry inference, a validation experiment was undertaken with 319 individuals from four geographically separated populations in China. Four Chinese populations were classified into different ancestry subgroups and 81.8% test individuals' ancestry could be inferred correctly. Our result showed that development of high ancestry informative InDels panel based on CE platform is a potential for individual ancestry inference among intracontinental populations.

Progress in Defining the Genetic Contribution to Type 2 Diabetes in Individuals of East Asian Ancestry.

PURPOSE OF REVIEW: Prevalence of type 2 diabetes (T2D) and progression of complications differ between worldwide populations. While obesity is a major contributing risk factor, variations in physiological manifestations, e.g., developing T2D at lower body mass index in some populations, suggest other contributing factors. Early T2D genetic associations were mostly discovered in European ancestry populations. This review describes the progression of genetic discoveries associated with T2D in individuals of East Asian ancestry in the last 10 years and highlights the shared genetic susceptibility between the population groups and additional insights into genetic contributions to T2D. RECENT FINDINGS: Through increased sample size and power, new genetic associations with T2D were discovered in East Asian ancestry populations, often with higher allele frequencies than European ancestry populations. As we continue to generate maps of T2D-associated variants across diverse populations, there will be a critical need to expand and diversify other omics resources to enable integration for clinical translation.

In search of TP53 mutational hot spots for Li-Fraumeni syndrome in Asian populations.

OBJECTIVE: Germline mutations of the TP53 tumour suppressor gene are the only known cause of the hereditary autosomal disorder called Li-Fraumeni syndrome (LFS). However, little information is available about TP53 pathogenic variants in Asian LFS patients, making it difficult to provide precise genetic counselling with regard to long-term cancer risk. We conducted a systematic review to gather relevant case-control studies exploring the association between TP53 polymorphisms and the incidence of cancer belonging to the LFS spectrum in Asian populations. METHOD: Systematic review and meta-analysis. The odds ratio was used as a summary effect measure to quantify the strength of the association between TP53 polymorphisms and cancer risk by means of random-effects meta-analysis. RESULTS: In total, 16 studies were included in this systematic review, with 13 studies (involving 10,645 cases and 28,288 controls) that enabled meta-analysis. The majority of the studies focused on a single-nucleotide variation at codon 72 in exon 4 (c.215C>G, p.Arg72Pro, rs1042522). Therefore, we tested either dominant, co-dominant, recessive, or heterozygous models and found that the p.Arg72Pro was not significantly associated with increased cancer risk in any of the models. CONCLUSION: We found the number of studies on cancers belonging to the LFS spectrum in Asia is very small. Thus, at the present time a meta-analysis approach is somewhat useful to identify germline TP53 mutations as potential markers of hereditary cancer associated with LFS in Asian populations.

Comparing the prediction of prostate biopsy outcome using the Chinese Prostate Cancer Consortium (CPCC) Risk Calculator and the Asian adapted Rotterdam European Randomized Study of Screening for Prostate Cancer (ERSPC) Risk Calculator in Chinese and European men.

PURPOSE: To externally validate the clinical utility of Chinese Prostate Cancer Consortium Risk Calculator (CPCC-RC) and Asian adapted Rotterdam European Randomized Study of Screening for Prostate Cancer Risk Calculator 3 (A-ERSPC-RC3) for prediction prostate cancer (PCa) and high-grade prostate cancer (HGPCa, Gleason Score ≥ 3 + 4) in both Chinese and European populations. MATERIALS AND METHODS: The Chinese clinical cohort, the European population-based screening cohort, and the European clinical cohort included 2,508, 3,616 and 617 prostate biopsy-naive men, respectively. The area under the receiver operating characteristic curve (AUC), calibration plot and decision curve analyses were applied in the analysis. RESULTS: The CPCC-RC's predictive ability for any PCa (AUC 0.77, 95% CI 0.75-0.79) was lower than the A-ERSPC-RC3 (AUC 0.79, 95% CI 0.77-0.81) in the European screening cohort (p < 0.001), but similar for HGPCa (p = 0.24). The CPCC-RC showed lower predictive accuracy for any PCa (AUC 0.65, 95% CI 0.61-0.70), but acceptable predictive accuracy for HGPCa (AUC 0.73, 95% CI 0.69-0.77) in the European clinical cohort. The A-ERSPC-RC3 showed an AUC of 0.74 (95% CI 0.72-0.76) in predicting any PCa, and a similar AUC of 0.74 (95% CI 0.72-0.76) in predicting HGPCa in Chinese cohort. In the Chinese population, decision curve analysis revealed a higher net benefit for CPCC-RC than A-ERSPC-RC3, while in the European screening and clinical cohorts, the net benefit was higher for A-ERSPC-RC3. CONCLUSIONS: The A-ERSPC-RC3 accurately predict the prostate biopsy in a contemporary Chinese multi-center clinical cohort. The CPCC-RC can predict accurately in a population-based screening cohort, but not in the European clinical cohort.

Pharmacogenetics of tamoxifen therapy in Asian populations: from genetic polymorphism to clinical outcomes.

BACKGROUND: Compared with western countries, Asian breast cancer patients have unique pathological and biological characteristics. Most of them are premenopausal women with HR positive. Tamoxifen as the first-line drug for premenopausal women with HR+ is involved in multiple enzymes and transporters during metabolizing and transporting process. Variants that cause decreased or inactive gene products leading to abnormal responses in tamoxifen therapy have well been studied in western countries, whereas such information is much less reported in Asian populations. OBJECTIVE: In order to elucidate the relationship between genetic variants and tamoxifen-induced individual drug reactions in different Asian populations and further identify genotypes/phenotypes with potential therapeutic significance. METHODS: We reviewed the frequencies of genetic variants in major enzymes and transporter genes involved in the metabolism and transport of tamoxifen across Asian populations as well as significant correlations between genotypes/metabolic phenotypes and metabolites concentrations or BC clinical outcomes. RESULTS: Significant inter-ethnic differences in allele frequencies was found among Asian populations, such as CYP2D6*4, *10, *41, CYP2C9*2, ABCB1 C3435T and SLCO1B1*5, and CYP2D6*10/*10 is the most common genotype correlated with adverse clinical outcomes. Moreover, we summarized the barriers and controversies of implementing pharmacogenetics in tamoxifen therapy and concluded that more population-specific pharmacogenetic studies are needed in the future. CONCLUSION: This review revealed more systematic pharmacogenomics of genes involved in the metabolism and transport besides CYP2D6, are required to optimize the genotyping strategies and guide the personalized tamoxifen therapy in Asian populations.

Genetic association between eNOS gene polymorphisms and risk of carotid atherosclerosis : A meta-analysis.

BACKGROUND: Endothelial nitric oxide synthase (eNOS) has been reported to be involved in the atherosclerotic process. A number of studies have investigated the association between eNOS gene polymorphisms and the risk of carotid atherosclerosis (CAS). However, the results are conflicting and inconclusive. The aim of this study was to evaluate precisely the association between the eNOS T786C, G894T, and 4a/4b polymorphisms and CAS risk. MATERIAL AND METHODS: A meta-analysis was carried out by retrieving relevant studies from PubMed, Embase, China National Knowledge Infrastructure (CNKI), and Cochrane databases without a restriction on publication year. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were used to describe the strength of the association with CAS. RESULTS: Data were obtained from eight case-control studies comprising 2975 cases and 2624 controls. Significant associations were detected between the allelic and recessive models of the eNOS T786C polymorphism (allelic: p = 0.04; OR, 95% CI = 1.57 [1.01, 2.44]; recessive: p = 0.03; OR, 95% CI = 1.53 [1.04, 2.24]), as well as the allelic and dominant models of the eNOS 4a/4b polymorphism, and CAS risk in an Asian subgroup (allelic: p = 0.02; OR, 95% CI = 1.49 [1.07, 2.07]; dominant: p = 0.01; OR, 95% CI = 1.50 [1.09, 2.05]), but not in a Caucasian subgroup (p > 0.05). No association was observed between the eNOS G894T polymorphism and CAS risk (p > 0.05). CONCLUSION: Our study provides evidence that the allelic and recessive models of the eNOS T786C polymorphism and the allelic and dominant models of the eNOS 4a/4b polymorphism may increase the risk of CAS in Asian populations.

AI-SNPs screening based on the whole genome data and research on genetic structure differences of subcontinent populations.

The genetic structure differences in population is one of the key elements in medical research involving multi-population samples. A set of ancestry-informative single nucleotide polymorphisms (AI-SNPs) can be utilized to analyze genetic component of a population, infer ancestral origin of individuals and pre-filter samples to reduce the impact of population genetic structure differences on medical research. However, most of the published studies were focused on revealing the differences between populations of continents or regions of a continent. In this paper, AI-SNPs were screened by calculating FST value in each pair of five East Asian populations: Japanese in Tokyo (JPT), Han Chinese in Beijing (CHB), Southern Han Chinese (CHS), Chinese Dai in Xishuangbanna (CDX) and Kinh in Ho Chi Minh City (KHV) in the 1000 Genomes Project phase 3 (GRCh37.p13) to analyze differences in subcontinent populations. The results demonstrate that the five East Asian populations in our study were assigned to three clusters: JPT, CHB and CHS, CDX and KHV. A set of AI-SNPs can be used for analysis of individual genetic composition and selection of representative individuals. Individuals with over 80% population representative genetic components have good representativeness of a population. This paper demonstrated the practical value of the method, which was performed to verify the ancestral composition and select representative samples with a panel of screened AI-SNPs by FST value, thereby reducing the influence of genetic structure differences in subcontinent populations on population-related medical research.

Association of sugar-sweetened beverage intake at 18 months and 5 years of age with adiposity outcomes at 6 years of age: the Singapore GUSTO mother-offspring cohort.

Consumption of sugar-sweetened beverages (SSB) by infants and young children are less explored in Asian populations. The Growing Up in Singapore Towards healthy Outcomes cohort study examined associations between SSB intake at 18 months and 5 years of age, with adiposity measures at 6 years of age. We studied Singaporean infants/children with SSB intake assessed by FFQ at 18 months of age (n 555) and 5 years of age (n 767). The median for SSB intakes is 28 (interquartile range 5·5-98) ml at 18 months of age and 111 (interquartile range 57-198) ml at 5 years of age. Association between SSB intake (100 ml/d increments and tertile categories) and adiposity measures (BMI standard deviation scores (sd units), sum of skinfolds (SSF)) and overweight/obesity status were examined using multivariable linear and Poisson regression models, respectively. After adjusting for confounders and additionally for energy intake, SSB intake at age 18 months were not significantly associated with later adiposity measures and overweight/obesity outcomes. In contrast, at age 5 years, SSB intake when modelled as 100 ml/d increments were associated with higher BMI by 0·09 (95 % CI 0·02, 0·16) sd units, higher SSF thickness by 0·68 (95 % CI 0·06, 1·44) mm and increased risk of overweight/obesity by 1·2 (95 % CI 1·07, 1·23) times at age 6 years. Trends were consistent with SSB intake modelled as categorical tertiles. In summary, SSB intake in young childhood is associated with higher risks of adiposity and overweight/obesity. Public health policies working to reduce SSB consumption need to focus on prevention programmes targeted at young children.

Maternal plasma vitamin B12 concentrations during pregnancy and infant cognitive outcomes at 2 years of age.

Evidence on long-term influences of maternal vitamin B12 deficiency or concentrations on infant cognition is limited. We examined associations between maternal plasma vitamin B12 and cognitive development in 24-month-old infants. Maternal plasma vitamin B12 concentrations were measured at 26-28 weeks' gestation; infant cognitive development was assessed with the Bayley Scales of Infant and Toddler Development-III at 24 months, for 443 mother-infant pairs from the Growing Up in Singapore Towards Healthy Outcomes cohort. Linear regressions adjusted for key confounders examined associations of maternal vitamin B12 with cognitive, receptive and expressive language, fine and gross motor subscales. Co-occurrence of maternal vitamin B12 with folate or vitamin B6 insufficiencies on child's cognition was explored. Average maternal plasma vitamin B12 concentrations was 220·5 ± 80·5 pmol/l; 15 % and 41 % of mothers were vitamin B12 deficient (<148 pmol/l) and insufficient (148-220·9 pmol/l), respectively. Infants of mothers with vitamin B12 deficiency had 0·42 (95 % CI -0·70, -0·14) sd lower cognitive scores, compared with infants of mothers with sufficient vitamin B12. Co-occurrence of maternal vitamins B12 and B6 insufficiencies was associated with 0·37 (95 % CI -0·69, -0·06) sd lower cognitive scores in infants compared with infants of mothers sufficient in both vitamins. No significant associations were observed with other subscales. Study findings suggest the possible need to ensure adequate vitamin B12 during pregnancy. The impact of co-occurrence of maternal B-vitamins insufficiencies on early cognitive development warrants further investigation.

Gefitinib provides similar effectiveness and improved safety than erlotinib for east Asian populations with advanced non-small cell lung cancer: a meta-analysis.

BACKGROUND: The first-generation epidermal growth factor receptor tyrosine kinase inhibitors gefitinib and erlotinib have both been proven effective for treating advanced non-small cell lung cancer (NSCLC), especially in East Asian patients. We conducted this meta-analysis to compare their efficacy and safety in treating advanced NSCLC in this population. METHODS: We systematically searched PubMed, ScienceDirect, The Cochrane Library, Scopus, Ovid MEDLINE, Embase, Web of Science, and Google Scholar for the relevant studies. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and adverse effects (AEs) were analyzed as primary endpoints. RESULTS: We identified 5829 articles, among which 31 were included in the final analysis. Both gefitinib and erlotinib were effective for treating advanced NSCLC, with comparable PFS (95% confidence interval [CI]: 0.97-1.10, p = 0.26), OS (95% CI: 0.89-1.21, p = 0.61), ORR (95% CI: 1.00-1.18, p = 0.06), and DCR (95% CI: 0.93-1.05, p = 0.68). Erlotinib induced a significantly higher rate of dose reduction (95% CI: 0.13-0.65, p = 0.002) and grade 3-5 AEs (95% CI: 0.27-0.71, p = 0.0008). In subgroup analysis of AEs, the erlotinib group had a significantly higher rate and severity of skin rash, nausea/vomiting, diarrhea, fatigue and stomatitis. CONCLUSIONS: With equal anti-tumor efficacy and fewer AEs compared with erlotinib, gefitinib is more suitable for treating advanced NSCLC in East Asian patients. Further large-scale, well-designed randomized controlled trials are warranted to confirm our findings.