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Genome-wide association study in Chinese identifies novel loci for blood pressure and hypertension.

ABSTRACT: Hypertension is a common disorder and the leading risk factor for cardiovascular disease and premature deaths worldwide. Genome-wide association studies (GWASs) in the European population have identified multiple chromosomal regions associated with blood pressure, and the identified loci altogether explain only a small fraction of the variance for blood pressure. The differences in environmental exposures and genetic background between Chinese and European populations might suggest potential different pathways of blood pressure regulation. To identify novel genetic variants affecting blood pressure variation, we conducted a meta-analysis of GWASs of blood pressure and hypertension in 11 816 subjects followed by replication studies including 69 146 additional individuals. We identified genome-wide significant (P < 5.0 × 10(-8)) associations with blood pressure, which included variants at three new loci (CACNA1D, CYP21A2, and MED13L) and a newly discovered variant near SLC4A7. We also replicated 14 previously reported loci, 8 (CASZ1, MOV10, FGF5, CYP17A1, SOX6, ATP2B1, ALDH2, and JAG1) at genome-wide significance, and 6 (FIGN, ULK4, GUCY1A3, HFE, TBX3-TBX5, and TBX3) at a suggestive level of P = 1.81 × 10(-3) to 5.16 × 10(-8). These findings provide new mechanistic insights into the regulation of blood pressure and potential targets for treatments.

SUBMITTER: Lu X

PROVIDER: S-EPMC4303798 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature

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Genome-wide association study in Chinese identifies novel loci for blood pressure and hypertension.

Lu Xiangfeng X Wang Laiyuan L Lin Xu X Huang Jianfeng J Charles Gu C C He Meian M Shen Hongbing H He Jiang J Zhu Jingwen J Li Huaixing H Hixson James E JE Wu Tangchun T Dai Juncheng J Lu Ling L Shen Chong C Chen Shufeng S He Lin L Mo Zengnan Z Hao Yongchen Y Mo Xingbo X Yang Xueli X Li Jianxin J Cao Jie J Chen Jichun J Fan Zhongjie Z Li Ying Y Zhao Liancheng L Li Hongfan H Lu Fanghong F Yao Cailiang C Yu Lin L Xu Lihua L Mu Jianjun J Wu Xianping X Deng Ying Y Hu Dongsheng D Zhang Weidong W Ji Xu X Guo Dongshuang D Guo Zhirong Z Zhou Zhengyuan Z Yang Zili Z Wang Renping R Yang Jun J Zhou Xiaoyang X Yan Weili W Sun Ningling N Gao Pingjin P Gu Dongfeng D

Human molecular genetics 20140923 3

Hypertension is a common disorder and the leading risk factor for cardiovascular disease and premature deaths worldwide. Genome-wide association studies (GWASs) in the European population have identified multiple chromosomal regions associated with blood pressure, and the identified loci altogether explain only a small fraction of the variance for blood pressure. The differences in environmental exposures and genetic background between Chinese and European populations might suggest potential dif ...[more]

PMID: 25249183

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Project description:Understanding how genomes encode complex cellular and organismal behaviors is an outstanding challenge of modern genetics. Unlike classical screening methods, analysis of the genetic variation that occurs naturally in wild populations can enable rapid, genome-scale trait mapping with a medium-throughput experimental design. Here we describe the results of the first genome-wide association analysis (GWAS) of a microbial eukaryote, using wild isolates of the filamentous fungus Neurospora crassa. We transcriptionally profiled each of 112 individuals collected in Louisiana and used RNA-seq data to genotype each strain at thousands of genetic loci genome-wide. We used these genotypes in a mapping analysis of microbial communication. In N. crassa, germinated asexual spores (germlings) sense the presence of other germlings, grow toward them in a coordinated fashion, and fuse. We evaluated germlings of each strain for their ability to chemically sense, chemotropically seek, and undergo cell fusion. GWAS identified one gene, NCU04379 (cse-1, encoding a homolog of neuronal calcium sensor), at which inheritance was strongly associated with the efficiency of germling communication. Deletion of cse-1 significantly lowered germling communication and fusion, and two genes encoding predicted binding partners of CSE-1 were also required for the communication trait. Additionally, mining our association results for signaling and secretion genes with a potential role in germling communication, we validated six more novel determinants of germling communication, including a secreted protease and two other genes whose deletion conferred a novel phenotype of increased communication and multi-germling fusion. These results establish protein secretion as a linchpin of germling communication in N. crassa and shed light on the regulation of communication molecules in this fungus. Our study demonstrates the power of population-genetic analyses for the rapid identification of genes contributing to complex traits in microbial species. 112 mycelial mRNA profiles of 16 hour wild type (WT) Neurospora crassa strains were generated by deep sequencing, using Illumina GAIIx.

Dataset Information

Genome-wide association study in Chinese identifies novel loci for blood pressure and hypertension.

Publications

Genome-wide association study in Chinese identifies novel loci for blood pressure and hypertension.

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