Genome-wide association study of plasma resistin levels identified rs1423096 and rs10401670 as possible functional variants in the Japanese population

2016 ◽  
Vol 48 (11) ◽  
pp. 874-881 ◽  
Author(s):  
Ryoichi Kawamura ◽  
Yasuharu Tabara ◽  
Akiko Tsukada ◽  
Michiya Igase ◽  
Jun Ohashi ◽  
...  
Keyword(s):  
Linkage Disequilibrium ◽  
Association Study ◽  
Japanese Population ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Luciferase Reporter ◽  
Strong Linkage Disequilibrium ◽  
Functional Variants ◽  
Genome Wide ◽  
A Genome

Resistin is a cytokine inducing insulin resistance in mice. We previously identified single nucleotide polymorphisms (SNPs) at −420 (rs1862513) and −358 (rs3219175) located in the human resistin gene ( RETN) promoter as strong determinants for circulating resistin in the Japanese population. The objective was to identify additional functional variants for circulating resistin. We conducted a genome-wide association study in 448 Japanese subjects. A peak association signal was found on chromosome 19 where RETN is located. The top-hit SNP was SNP −358 G>A, followed by rs1423096 C>T, SNP −420 C>G, and rs10401670 C>T ( P = 5.39×10−47, 1.81×10−22, 2.09×10−16, and 9.25×10−15, respectively). Meta-analysis including another two independent general Japanese populations showed that circulating resistin was most strongly associated with SNP-358, followed by SNP-420, rs1423096, and rs10401670. Rs1423096 and rs10401670 were located in the 3′-region of RETN and were in strong linkage disequilibrium. Although these SNPs were also in linkage disequilibrium with the promoter SNPs, conditional and haplotype association analyses identified rs1423096 and rs10401670 as independent determinants for circulating resistin. Functionally, nuclear proteins specifically recognized T but not C at rs10401670 as evidenced by an electrophoretic mobility shift assay. The promoter activity of a luciferase reporter with T at either rs1423096 or rs10401670 was lower than that with C in THP-1 human monocytes. Therefore, rs1423096 and rs10401670, in addition to SNP-420 and SNP-358, were identified as possible functional variants affecting circulating resistin by the genome-wide search in the Japanese population.

scholarly journals A Genome-Wide Association Study for Hypertensive Kidney Disease in Korean Men

Genes ◽  
2021 ◽  
Vol 12 (5) ◽  
pp. 751
Author(s):  
Hye-Rim Kim ◽  
Hyun-Seok Jin ◽  
Yong-Bin Eom
Keyword(s):  
Blood Pressure ◽  
Kidney Disease ◽  
Association Study ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Integrated Analysis ◽  
Eqtl Analysis ◽  
Strong Linkage Disequilibrium ◽  
Genome Wide ◽  
A Genome

Hypertension is one of the major risk factors for chronic kidney disease (CKD), and the coexistence of hypertension and CKD increases morbidity and mortality. Although many genetic factors have been identified separately for hypertension and kidney disease, studies specifically focused on hypertensive kidney disease (HKD) have been rare. Therefore, this study aimed to identify loci or genes associated with HKD. A genome-wide association study (GWAS) was conducted using two Korean cohorts, the Health Examinee (HEXA) and Korean Association REsource (KARE). Consequently, 19 single nucleotide polymorphisms (SNPs) were found to be significantly associated with HKD in the discovery and replication phases (p < 5 × 10−8, p < 0.05, respectively). We further analyzed HKD-related traits such as the estimated glomerular filtration rate (eGFR), creatinine, blood urea nitrogen (BUN), systolic blood pressure (SBP) and diastolic blood pressure (DBP) at the 14q21.2 locus, which showed a strong linkage disequilibrium (LD). Expression quantitative trait loci (eQTL) analysis was also performed to determine whether HKD-related SNPs affect gene expression changes in glomerular and arterial tissues. The results suggested that the FANCM gene may affect the development of HKD through an integrated analysis of eQTL and GWAS and was the most significantly associated candidate gene. Taken together, this study indicated that the FANCM gene is involved in the pathogenesis of HKD. Additionally, our results will be useful in prioritizing other genes for further experiments.

scholarly journals Replication of a genome-wide association study of panic disorder in a Japanese population

2009 ◽  
Vol 55 (2) ◽  
pp. 91-96 ◽  
Author(s):  
Takeshi Otowa ◽  
Hisashi Tanii ◽  
Nagisa Sugaya ◽  
Eiji Yoshida ◽  
Ken Inoue ◽  
...  
Keyword(s):  
Panic Disorder ◽  
Association Study ◽  
Japanese Population ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Genome Wide ◽  
A Genome

A genome-wide association study identifies two susceptibility loci for duodenal ulcer in the Japanese population

2012 ◽  
Vol 44 (4) ◽  
pp. 430-434 ◽  
Author(s):  
Chizu Tanikawa ◽  
Yuji Urabe ◽  
Keitaro Matsuo ◽  
Michiaki Kubo ◽  
Atsushi Takahashi ◽  
...  
Keyword(s):  
Duodenal Ulcer ◽  
Association Study ◽  
Japanese Population ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Susceptibility Loci ◽  
Genome Wide ◽  
A Genome

A genome-wide association study identifies two new susceptibility loci for lung adenocarcinoma in the Japanese population

2012 ◽  
Vol 44 (8) ◽  
pp. 900-903 ◽  
Author(s):  
Kouya Shiraishi ◽  
Hideo Kunitoh ◽  
Yataro Daigo ◽  
Atsushi Takahashi ◽  
Koichi Goto ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Association Study ◽  
Japanese Population ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Susceptibility Loci ◽  
Genome Wide ◽  
A Genome

scholarly journals A genome-wide association study identifies a novel candidate locus at the DLGAP1 gene with susceptibility to resistant hypertension in the Japanese population

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yasuo Takahashi ◽  
Keiko Yamazaki ◽  
Yoichiro Kamatani ◽  
Michiaki Kubo ◽  
Koichi Matsuda ◽  
...  
Keyword(s):  
Association Study ◽  
Resistant Hypertension ◽  
Japanese Population ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Neuron Development ◽  
Candidate Locus ◽  
Asian Populations ◽  
Genome Wide ◽  
A Genome

AbstractNumerous genetic variants associated with hypertension and blood pressure are known, but there is a paucity of evidence from genetic studies of resistant hypertension, especially in Asian populations. To identify novel genetic loci associated with resistant hypertension in the Japanese population, we conducted a genome-wide association study with 2705 resistant hypertension cases and 21,296 mild hypertension controls, all from BioBank Japan. We identified one novel susceptibility candidate locus, rs1442386 on chromosome 18p11.3 (DLGAP1), achieving genome-wide significance (odds ratio (95% CI) = 0.85 (0.81–0.90), P = 3.75 × 10−8) and 18 loci showing suggestive association, including rs62525059 of 8q24.3 (CYP11B2) and rs3774427 of 3p21.1 (CACNA1D). We further detected biological processes associated with resistant hypertension, including chemical synaptic transmission, regulation of transmembrane transport, neuron development and neurological system processes, highlighting the importance of the nervous system. This study provides insights into the etiology of resistant hypertension in the Japanese population.

scholarly journals Genome wide association study of HTLV-1–associated myelopathy/tropical spastic paraparesis in the Japanese population

2021 ◽  
Vol 118 (11) ◽  
pp. e2004199118
Author(s):  
Marina Penova ◽  
Shuji Kawaguchi ◽  
Jun-ichirou Yasunaga ◽  
Takahisa Kawaguchi ◽  
Tomoo Sato ◽  
...  
Keyword(s):  
Amino Acid ◽  
Association Study ◽  
Proviral Load ◽  
Odds Ratio ◽  
Japanese Population ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Genome Wide ◽  
A Genome ◽  
Increased Risk

HTLV-1–associated myelopathy (HAM/TSP) is a chronic and progressive inflammatory disease of the central nervous system. The aim of our study was to identify genetic determinants related to the onset of HAM/TSP in the Japanese population. We conducted a genome-wide association study comprising 753 HAM/TSP patients and 899 asymptomatic HTLV-1 carriers. We also performed comprehensive genotyping of HLA-A, -B, -C, -DPB1, -DQB1, and -DRB1 genes using next-generation sequencing technology for 651 HAM/TSP patients and 804 carriers. A strong association was observed in HLA class I (P = 1.54 × 10−9) and class II (P = 1.21 × 10−8) loci with HAM/TSP. Association analysis using HLA genotyping results showed that HLA-C*07:02 (P = 2.61 × 10−5), HLA-B*07:02 (P = 4.97 × 10−10), HLA-DRB1*01:01 (P = 1.15 × 10−9) and HLA-DQB1*05:01 (P = 2.30 × 10−9) were associated with disease risk, while HLA-B*40:06 (P = 3.03 × 10−5), HLA-DRB1*15:01 (P = 1.06 × 10−5) and HLA-DQB1*06:02 (P = 1.78 × 10−6) worked protectively. Logistic regression analysis identified amino acid position 7 in the G-BETA domain of HLA-DRB1 as strongly associated with HAM/TSP (P = 9.52 × 10−10); individuals homozygous for leucine had an associated increased risk of HAM/TSP (odds ratio, 9.57), and proline was protective (odds ratio, 0.65). Both associations were independent of the known risk associated with proviral load. DRB1-GB-7-Leu was not significantly associated with proviral load. We have identified DRB1-GB-7-Leu as a genetic risk factor for HAM/TSP development independent of proviral load. This suggests that the amino acid residue may serve as a specific marker to identify the risk of HAM/TSP even without knowledge of proviral load. In light of its allele frequency worldwide, this biomarker will likely prove useful in HTLV-1 endemic areas across the globe.

scholarly journals Genome-wide association study identifies the PLAG1-OXR1 region on BTA14 for carcass meat yield in cattle

2019 ◽  
Vol 51 (5) ◽  
pp. 137-144 ◽  
Author(s):  
Rui Zhang ◽  
Jian Miao ◽  
Yuxin Song ◽  
Wengang Zhang ◽  
Lingyang Xu ◽  
...  
Keyword(s):  
Association Study ◽  
Genome Wide Association Study ◽  
Carcass Traits ◽  
Coiled Coil ◽  
Genome Wide Association ◽  
Strong Linkage Disequilibrium ◽  
Meat Yield ◽  
Fatty Acid Binding ◽  
Genome Wide ◽  
A Genome

Carcass meat yield is an important carcass trait that contributes to the production efficiency and economic benefits in beef cattle. It is therefore critical to identify quantitative trait loci associated with carcass traits to enable selection. Our previous studies have identified several causal variants within the pleomorphic adenoma gene 1 ( PLAG1) and coiled-coil-helix-coiled-coil-helix domain-containing 7 ( CHCHD7) genes on BTA14 for carcass traits in Chinese Simmental. In the current study, we carried out a genome-wide association study for carcass meat yield in 472 Wagyu cattle with Bovine HD SNP array. Our results showed that 27 single nucleotide polymorphisms (SNPs) were identified for tenderloin weight (TDW), striploin weight (SPW), chuck roll weight (CRW), bicep weight (BPW), knuckle weight (KCW), and flank steak weight (FSW) in Wagyu cattle. Of these SNPs, 10 distinct SNPs were detected within the oxidation resistance 1 ( OXR1), fatty acid binding protein 5 ( FABP5), TNF receptor superfamily member 11b ( TNFRSF11B), and zinc finger CCCH-type containing 3 ( ZC3H3) genes on BTA14. Notably, three significant SNPs, BovineHD1400016738, BovineHD1400016743, and BovineHD1400016665 within OXR1, were shown strong linkage disequilibrium (r2 > 0.8) and significantly associated with CRW ( P = 1.37 × 10−8 ~ 1.94 × 10−8). Moreover, Ingenuity Pathway Analysis showed that OXR1, FABP5, and CAP1A genes were involved in a single network and FABP5 may regulate the expression of OXR1 gene via node gene, peroxisome proliferator-activated receptor gamma ( PPARG). Overall, this study suggests that OXR1 and FABP5 are candidate genes affecting carcass traits in Wagyu and the PLAG1-OXR1 region on BTA14 as a putative susceptibility locus for carcass meat yield for both Chinese Simmental and Wagyu.

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