Lu, X., Wang, L., Chen, S., He, L., Yang, X., Shi, Y. et al. Genome-wide association study in Han Chinese identifies four new susceptibility loci for coronary artery disease. Nat. Genet. 44, 890-894

State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center of Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Nature Genetics (Impact Factor: 29.35). 07/2012; 44(8):890-4. DOI: 10.1038/ng.2337
Source: PubMed


We performed a meta-analysis of 2 genome-wide association studies of coronary artery disease comprising 1,515 cases and 5,019 controls followed by replication studies in 15,460 cases and 11,472 controls, all of Chinese Han ancestry. We identify four new loci for coronary artery disease that reached the threshold of genome-wide significance (P < 5 × 10(-8)). These loci mapped in or near TTC32-WDR35, GUCY1A3, C6orf10-BTNL2 and ATP2B1. We also replicated four loci previously identified in European populations (in or near PHACTR1, TCF21, CDKN2A-CDKN2B and C12orf51). These findings provide new insights into pathways contributing to the susceptibility for coronary artery disease in the Chinese Han population.

Download full-text


Available from: Xiangfeng Lu
  • Source
    • "represent signals independent from the major psoriasis HLA-C*0602 risk allele, an observation reported before (Davies et al., 2012; Feng et al., 2009). Effects on CAD and psoriasis risk were into the same direction, but the reported effect sizes on CAD are modest (OR<1.2) (Lu et al., 2012). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Psoriasis has been linked to cardiometabolic diseases, but epidemiological findings are inconsistent. We investigated the association between psoriasis and cardiometabolic outcomes in a German cross-sectional study (n=4.185) and a prospective cohort of German Health Insurance beneficiaries (n=1.811.098). A potential genetic overlap was explored using genome-wide data from >22.000 coronary artery disease (CAD) and >4.000 psoriasis cases, and with a dense genotyping study of cardiometabolic risk loci on 927 psoriasis cases and 3.717 controls. Controlling for major confounders, in the cross-sectional analysis psoriasis was significantly associated with type 2 diabetes (T2D, adjusted odd's ratio OR=2.36; 95% confidence interval CI=1.26-4.41) and myocardial infarction (MI, OR=2.26, 95% CI=1.03-4.96). In the longitudinal study, psoriasis slightly increased the risk for incident T2D (adjusted relative risk RR=1.11; 95%CI=1.08-1.14) and MI (RR=1.14; 95%CI=1.06-1.22), with highest risk increments in systemically treated psoriasis, which accounted for 11 and 17 excess cases of T2D and MI per 10,000 person-years. Except for weak signals from within the MHC, there was no evidence for genetic risk loci shared between psoriasis and cardiometabolic traits. Our findings suggest that psoriasis, in particular severe psoriasis, increases risk for T2D and MI, and that the genetic architecture of psoriasis and cardiometabolic traits is largely distinct.Journal of Investigative Dermatology accepted article preview online, 19 January 2015. doi:10.1038/jid.2015.8.
    Full-text · Article · Jan 2015 · Journal of Investigative Dermatology
  • Source
    • "Inactivation of CDKN2A, through loss of heterozygosity or hypermethylation of its promoter, has been reported in endometriosis and endometrial cancer (Goumenou et al., 2000; Martini et al., 2002; Guida et al., 2009). SNPs in or near the CDKN2B-AS1 locus have been associated with many other traits and disease (Supplementary data, Table SI), with a number in LD (r2 > 0.2) with the endometriosis SNPs (Fig. 4), including rs1063192 and rs2157719 with glaucoma (Osman et al., 2012; Wiggs et al., 2012), rs4977756 with glioma (Rajaraman et al., 2012), rs10757269 with ankle-brachial index (Murabito et al., 2012), rs6475606 and rs10757272 with intracranial aneurysm (Foroud et al., 2012; Low et al., 2012), rs1537370 with coronary artery calcification (van Setten et al., 2013) and rs7865618, rs10757274, rs1333042 and rs944797 with coronary heart disease (Wild et al., 2011; Lu et al., 2012; Takeuchi et al., 2012; Lee et al., 2013); because of these diverse associations, its function is an area of research for many investigators. "
    [Show abstract] [Hide abstract]
    ABSTRACT: BACKGROUND Endometriosis is a heritable common gynaecological condition influenced by multiple genetic and environmental factors. Genome-wide association studies (GWASs) have proved successful in identifying common genetic variants of moderate effects for various complex diseases. To date, eight GWAS and replication studies from multiple populations have been published on endometriosis. In this review, we investigate the consistency and heterogeneity of the results across all the studies and their implications for an improved understanding of the aetiology of the condition.
    Full-text · Article · Mar 2014 · Human Reproduction Update
  • Source
    • "Recent studies have demonstrated that the WDR35 gene is involved in several human diseases such as type 2 diabetes [31], acute lymphoblastic leukemia [32], coronary artery disease [33], and Sensenbrenner syndrome [34]. However, the regulation of WDR35 expression by intracellular signaling pathways has not been fully elucidated. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The family of WD repeat proteins comprises a large number of proteins and is involved in a wide variety of cellular processes such as signal transduction, cell growth, proliferation, and apoptosis. Bupivacaine is a sodium channel blocker administered for local infiltration, nerve block, epidural, and intrathecal anesthesia. Recently, we reported that bupivacaine induces reactive oxygen species (ROS) generation and p38 mitogen-activated protein kinase (MAPK) activation, resulting in an increase in the expression of WD repeat-containing protein 35 (WDR35) in mouse neuroblastoma Neuro2a cells. It has been shown that ROS activate MAPK through phosphorylation, followed by activation of nuclear factor-kappa B (NF-κB) and activator protein 1 (AP-1). The present study was undertaken to test whether NF-κB and c-Jun/AP-1 are involved in bupivacaine-induced WDR35 expression in Neuro2a cells. Bupivacaine activated both NF-κB and c-Jun in Neuro2a cells. APDC, an NF-κB inhibitor, attenuated the increase in NF-κB activity and WDR35 protein expression in bupivacaine-treated Neuro2a cells. GW9662, a selective peroxisome proliferator-activated receptor-γ antagonist, enhanced the increase in NF-κB activity and WDR35 protein expression in bupivacaine-treated Neuro2a cells. In contrast, c-Jun siRNA did not inhibit the bupivacaine-induced increase in WDR35 mRNA expression. These results indicate that bupivacaine induces the activation of transcription factors NF-κB and c-Jun/AP-1 in Neuro2a cells, while activation of NF-κB is involved in bupivacaine-induced increases in WDR35 expression.
    Full-text · Article · Jan 2014 · PLoS ONE
Show more