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Meta-analysis of genome-wide association studies of adult height in East Asians identifies 17 novel loci.

ABSTRACT: Human height is associated with risk of multiple diseases and is profoundly determined by an individual's genetic makeup and shows a high degree of ethnic heterogeneity. Large-scale genome-wide association (GWA) analyses of adult height in Europeans have identified nearly 180 genetic loci. A recent study showed high replicability of results from Europeans-based GWA studies in Asians; however, population-specific loci may exist due to distinct linkage disequilibrium patterns. We carried out a GWA meta-analysis in 93 926 individuals from East Asia. We identified 98 loci, including 17 novel and 81 previously reported loci, associated with height at P < 5 × 10(-8), together explaining 8.89% of phenotypic variance. Among the newly identified variants, 10 are commonly distributed (minor allele frequency, MAF > 5%) in Europeans, with comparable frequencies with in Asians, and 7 single-nucleotide polymorphisms are with low frequency (MAF < 5%) in Europeans. In addition, our data suggest that novel biological pathway such as the protein tyrosine phosphatase family is involved in regulation of height. The findings from this study considerably expand our knowledge of the genetic architecture of human height in Asians.

SUBMITTER: He M

PROVIDER: S-EPMC4351379 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature

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Meta-analysis of genome-wide association studies of adult height in East Asians identifies 17 novel loci.

He Meian M Xu Min M Zhang Ben B Liang Jun J Chen Peng P Lee Jong-Young JY Johnson Todd A TA Li Huaixing H Yang Xiaobo X Dai Juncheng J Liang Liming L Gui Lixuan L Qi Qibin Q Huang Jinyan J Li Yanping Y Adair Linda S LS Aung Tin T Cai Qiuyin Q Cheng Ching-Yu CY Cho Myeong-Chan MC Cho Yoon Shin YS Chu Minjie M Cui Bin B Gao Yu-Tang YT Go Min Jin MJ Gu Dongfeng D Gu Weiqiong W Guo Huan H Hao Yongchen Y Hong Jie J Hu Zhibin Z Hu Yanling Y Huang Jianfeng J Hwang Joo-Yeon JY Ikram Mohammad Kamran MK Jin Guangfu G Kang Dae-Hee DH Khor Chiea Chuen CC Kim Bong-Jo BJ Kim Hung Tae HT Kubo Michiaki M Lee Jeannette J Lee Juyoung J Lee Nanette R NR Li Ruoying R Li Jun J Liu JianJun J Longe Jirong J Lu Wei W Lu Xiangfeng X Miao Xiaoping X Okada Yukinori Y Ong Rick Twee-Hee RT Qiu Gaokun G Seielstad Mark M Sim Xueling X Song Huaidong H Takeuchi Fumihiko F Tanaka Toshihiro T Taylor Phil R PR Wang Laiyuan L Wang Weiqing W Wang Yiqin Y Wu Chen C Wu Ying Y Xiang Yong-Bing YB Yamamoto Ken K Yang Handong H Liao Ming M Yokota Mitsuhiro M Young Terri T Zhang Xiaomin X Kato Norihiro N Wang Qing K QK Zheng Wei W Hu Frank B FB Lin Dongxin D Shen Hongbing H Teo Yik Ying YY Mo Zengnan Z Wong Tien Yin TY Lin Xu X Mohlke Karen L KL Ning Guang G Tsunoda Tatsuhiko T Han Bok-Ghee BG Shu Xiao-Ou XO Tai E Shyong ES Wu Tangchun T Qi Lu L

Human molecular genetics 20141126 6

Human height is associated with risk of multiple diseases and is profoundly determined by an individual's genetic makeup and shows a high degree of ethnic heterogeneity. Large-scale genome-wide association (GWA) analyses of adult height in Europeans have identified nearly 180 genetic loci. A recent study showed high replicability of results from Europeans-based GWA studies in Asians; however, population-specific loci may exist due to distinct linkage disequilibrium patterns. We carried out a GWA ...[more]

PMID: 25429064

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Project description:Background & aimsGenome-wide association studies (GWASs) have associated approximately 50 loci with risk of colorectal cancer (CRC)-nearly one third of these loci were initially associated with CRC in studies conducted in East Asian populations. We conducted a GWAS of East Asians to identify CRC risk loci and evaluate the generalizability of findings from GWASs of European populations to Asian populations.MethodsWe analyzed genetic data from 22,775 patients with CRC (cases) and 47,731 individuals without cancer (controls) from 14 studies in the Asia Colorectal Cancer Consortium. First, we performed a meta-analysis of 7 GWASs (10,625 cases and 34,595 controls) and identified 46,554 promising risk variants for replication by adding them to the Multi-Ethnic Global Array (MEGA) for genotype analysis in 6445 cases and 7175 controls. These data were analyzed, along with data from an additional 5705 cases and 5961 controls genotyped using the OncoArray. We also obtained data from 57,976 cases and 67,242 controls of European descent. Variants at identified risk loci were functionally annotated and evaluated in correlation with gene expression levels.ResultsA meta-analyses of all samples from people of Asian descent identified 13 loci and 1 new variant at a known locus (10q24.2) associated with risk of CRC at the genome-wide significance level of P < 5 × 10-8. We did not perform experiments to replicate these associations in additional individuals of Asian ancestry. However, the lead risk variant in 6 of these loci was also significantly associated with risk of CRC in European descendants. A strong association (44%-75% increase in risk per allele) was found for 2 low-frequency variants: rs201395236 at 1q44 (minor allele frequency, 1.34%) and rs77969132 at 12p11.21 (minor allele frequency, 1.53%). For 8 of the 13 associated loci, the variants with the highest levels of significant association were located inside or near the protein-coding genes L1TD1, EFCAB2, PPP1R21, SLCO2A1, HLA-G, NOTCH4, DENND5B, and GNAS. For other intergenic loci, we provided evidence for the possible involvement of the genes ALDH7A1, PRICKLE1, KLF5, WWOX, and GLP2R. We replicated findings for 41 of 52 previously reported risk loci.ConclusionsWe showed that most of the risk loci previously associated with CRC risk in individuals of European descent were also associated with CRC risk in East Asians. Furthermore, we identified 13 loci significantly associated with risk for CRC in Asians. Many of these loci contained genes that regulate the immune response, Wnt signaling to β-catenin, prostaglandin E2 catabolism, and cell pluripotency and proliferation. Further analyses of these genes and their variants is warranted, particularly for the 8 loci for which the lead CRC risk variants were not replicated in persons of European descent.

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Meta-analysis of genome-wide association studies of adult height in East Asians identifies 17 novel loci.

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Meta-analysis of genome-wide association studies of adult height in East Asians identifies 17 novel loci.

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