Association analyses of East Asian individuals and trans-ancestry analyses with European individuals reveal new loci associated with cholesterol and triglyceride levels

Large-scale meta-analyses of genome-wide association studies (GWAS) have identified >175 loci associated with fasting cholesterol levels, including total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG). With differences in linkage disequilibrium (LD) structure and allele frequencies between ancestry groups, studies in additional large samples may detect new associations. We conducted staged GWAS meta-analyses in up to 69,414 East Asian individuals from 24 studies with participants from Japan, the Philippines, Korea, China, Singapore, and Taiwan. These meta-analyses identified (P < 5 × 10-8) three novel loci associated with HDL-C near CD163-APOBEC1 (P = 7.4 × 10-9), NCOA2 (P = 1.6 × 10-8), and NID2-PTGDR (P = 4.2 × 10-8), and one novel locus associated with TG near WDR11-FGFR2 (P = 2.7 × 10-10). Conditional analyses identified a second signal near CD163-APOBEC1. We then combined results from the East Asian meta-analysis with association results from up to 187,365 European individuals from the Global Lipids Genetics Consortium in a trans-ancestry meta-analysis. This analysis identified (log10Bayes Factor ≥6.1) eight additional novel lipid loci. Among the twelve total loci identified, the index variants at eight loci have demonstrated at least nominal significance with other metabolic traits in prior studies, and two loci exhibited coincident eQTLs (P < 1 × 10-5) in subcutaneous adipose tissue for BPTF and PDGFC. Taken together, these analyses identified multiple novel lipid loci, providing new potential therapeutic targets

Meta-analysis of genome-wide association studies in East Asian-ancestry populations identifies four new loci for body mass index

Recent genetic association studies have identified 55 genetic loci associated with obesity or body mass index (BMI). The vast majority, 51 loci, however, were identified in European-ancestry populations. We conducted a meta-analysis of associations between BMI and ∼2.5 million genotyped or imputed single nucleotide polymorphisms among 86 757 individuals of Asian ancestry, followed by in silico and de novo replication among 7488–47 352 additional Asian-ancestry individuals. We identified four novel BMI-associated loci near the KCNQ1 (rs2237892, P = 9.29 × 10−13), ALDH2/MYL2 (rs671, P = 3.40 × 10−11; rs12229654, P = 4.56 × 10−9), ITIH4 (rs2535633, P = 1.77 × 10−10) and NT5C2 (rs11191580, P = 3.83 × 10−8) genes. The association of BMI with rs2237892, rs671 and rs12229654 was significantly stronger among men than among women. Of the 51 BMI-associated loci initially identified in European-ancestry populations, we confirmed eight loci at the genome-wide significance level (P < 5.0 × 10−8) and an additional 14 at P < 1.0 × 10−3 with the same direction of effect as reported previously. Findings from this analysis expand our knowledge of the genetic basis of obesity

Impact of the Operations of Group Practice Centers on Residents' Health-An Empirical Study of Taitung County

[[abstract]]目的 比較台東縣在74至79年間分別於太麻里鄉、大武鄉、長濱鄉與鹿野鄉四個鄉開辦群體醫療執業中心後，民眾健康狀況是否改善。 方法 以可避免死亡疾病死亡率做爲健康之負面測量指標，利用60至89年衛生署死因檔計算各年度標準化死亡佔率，並採用時間數列介入分析方法進行評估分析。 結果 除長濱鄉外，其他三個鄉在設置群醫中心後可避免死亡疾病死亡佔率均呈現顯著下降的改善情況，其下降值分別爲鹿野鄉1.71、大武鄉3.02、太麻里鄉3.45。然而在對照組部分，亦有部分鄉鎮分別在不同指標呈現顯著下降，但其下降值均比實施群醫中心的鄉來得小。 結論 群醫中心開辦對於偏遠地區醫療服務可近性有所提昇，並有改善民眾健康的效果，尤其是對於健康弱勢的兒童部分，因此推行群醫中心或委請醫療院所支遠山地離島、偏遠地區的醫療支援計劃可以再進一步的評估後，考慮推廣擴大。 Objective The purpose of this study was to evaluate the effect of operation of group practice centers on residents' health among Taimali, Dawu, Changbin, and Luye township in Taitung county between 1985 and 1990. Methods The avoidable death mortality was employed as adverse measurement of health. Age standardizes mortality between 1971 and 2000 were calculated from cause of death data provided by Department of Health. The interrupted time series intervention analysis was used to determine whether operation of group practice centers resulted in any significant change in avoidable mortality. Results: There were significant decreases of avoidable mortality in Luye (-1.71), Dawu (-3.02), and Taimali (-3.45) but in Changbin township. Eventhough there were also significant decreases in some control townships, but the effects were slightly then these townships with operation of group practice center. Conclusions The operations of group practice centers may result in improve accessibility and residents' health among remote districts, especially in children. To provide medical services via group practice center or HOM should be add after further details research support

Meta-analysis of genome-wide association studies in East Asian-ancestry populations identifies four new loci for body mass index.

Recent genetic association studies have identified 55 genetic loci associated with obesity or body mass index (BMI). The vast majority, 51 loci, however, were identified in European-ancestry populations. We conducted a meta-analysis of associations between BMI and ∼2.5 million genotyped or imputed single nucleotide polymorphisms among 86 757 individuals of Asian ancestry, followed by in silico and de novo replication among 7488-47 352 additional Asian-ancestry individuals. We identified four novel BMI-associated loci near the KCNQ1 (rs2237892, P = 9.29 × 10(-13)), ALDH2/MYL2 (rs671, P = 3.40 × 10(-11); rs12229654, P = 4.56 × 10(-9)), ITIH4 (rs2535633, P = 1.77 × 10(-10)) and NT5C2 (rs11191580, P = 3.83 × 10(-8)) genes. The association of BMI with rs2237892, rs671 and rs12229654 was significantly stronger among men than among women. Of the 51 BMI-associated loci initially identified in European-ancestry populations, we confirmed eight loci at the genome-wide significance level (P &lt; 5.0 × 10(-8)) and an additional 14 at P &lt; 1.0 × 10(-3) with the same direction of effect as reported previously. Findings from this analysis expand our knowledge of the genetic basis of obesity

Meta-analysis of genome-wide association studies in East Asian-ancestry populations identifies four new loci for body mass index

© The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: [email protected]. Recent genetic association studies have identified 55 genetic loci associated with obesity or body mass index (BMI). The vast majority, 51 loci, however, were identified in European-ancestry populations. We conducted a meta-analysis of associations between BMI and ∼2.5 million genotyped or imputed single nucleotide polymorphisms among 86 757 individuals of Asian ancestry, followed by in silico and de novo replication among 7488-47 352 additional Asian-ancestry individuals. We identified four novel BMI-associated loci near the KCNQ1 (rs2237892, P = 9.29 × 10(-13)), ALDH2/MYL2 (rs671, P = 3.40 × 10(-11); rs12229654, P = 4.56 × 10(-9)), ITIH4 (rs2535633, P = 1.77 × 10(-10)) and NT5C2 (rs11191580, P = 3.83 × 10(-8)) genes. The association of BMI with rs2237892, rs671 and rs12229654 was significantly stronger among men than among women. Of the 51 BMI-associated loci initially identified in European-ancestry populations, we confirmed eight loci at the genome-wide significance level (P < 5.0 × 10(-8)) and an additional 14 at P < 1.0 × 10(-3) with the same direction of effect as reported previously. Findings from this analysis expand our knowledge of the genetic basis of obesity