scholarly journals Korean Genome Project: 1094 Korean personal genomes with clinical information

2020 ◽  
Vol 6 (22) ◽  
pp. eaaz7835 ◽  
Author(s):  
Sungwon Jeon ◽  
Youngjune Bhak ◽  
Yeonsong Choi ◽  
Yeonsu Jeon ◽  
Seunghoon Kim ◽  
...  
Keyword(s):  
Genome Wide Association Study ◽  
Imputation Accuracy ◽  
Clinical Information ◽  
Genome Project ◽  
Single Nucleotide Variants ◽  
Single Nucleotide ◽  
Genome Wide ◽  
A Genome ◽  
Whole Genomes ◽  
Personal Genomes

We present the initial phase of the Korean Genome Project (Korea1K), including 1094 whole genomes (sequenced at an average depth of 31×), along with data of 79 quantitative clinical traits. We identified 39 million single-nucleotide variants and indels of which half were singleton or doubleton and detected Korean-specific patterns based on several types of genomic variations. A genome-wide association study illustrated the power of whole-genome sequences for analyzing clinical traits, identifying nine more significant candidate alleles than previously reported from the same linkage disequilibrium blocks. Also, Korea1K, as a reference, showed better imputation accuracy for Koreans than the 1KGP panel. As proof of utility, germline variants in cancer samples could be filtered out more effectively when the Korea1K variome was used as a panel of normals compared to non-Korean variome sets. Overall, this study shows that Korea1K can be a useful genotypic and phenotypic resource for clinical and ethnogenetic studies.

scholarly journals Combination of Genome-Wide Polymorphisms and Copy Number Variations of Pharmacogenes in Koreans

2021 ◽  
Vol 11 (1) ◽  
pp. 33
Author(s):  
Nayoung Han ◽  
Jung Mi Oh ◽  
In-Wha Kim
Keyword(s):  
Copy Number ◽  
Genome Wide Association Study ◽  
Copy Number Gain ◽  
Copy Number Variations ◽  
Gene Gain ◽  
Single Nucleotide Variants ◽  
Single Nucleotide ◽  
Haplotype Blocks ◽  
Genome Wide ◽  
Control And Prevention

For predicting phenotypes and executing precision medicine, combination analysis of single nucleotide variants (SNVs) genotyping with copy number variations (CNVs) is required. The aim of this study was to discover SNVs or common copy CNVs and examine the combined frequencies of SNVs and CNVs in pharmacogenes using the Korean genome and epidemiology study (KoGES), a consortium project. The genotypes (N = 72,299) and CNV data (N = 1000) were provided by the Korean National Institute of Health, Korea Centers for Disease Control and Prevention. The allele frequencies of SNVs, CNVs, and combined SNVs with CNVs were calculated and haplotype analysis was performed. CYP2D6 rs1065852 (c.100C>T, p.P34S) was the most common variant allele (48.23%). A total of 8454 haplotype blocks in 18 pharmacogenes were estimated. DMD ranked the highest in frequency for gene gain (64.52%), while TPMT ranked the highest in frequency for gene loss (51.80%). Copy number gain of CYP4F2 was observed in 22 subjects; 13 of those subjects were carriers with CYP4F2*3 gain. In the case of TPMT, approximately one-half of the participants (N = 308) had loss of the TPMT*1*1 diplotype. The frequencies of SNVs and CNVs in pharmacogenes were determined using the Korean cohort-based genome-wide association study.

Bisphosphonate-related osteonecrosis of the jaw is associated with polymorphisms of the cytochrome P450 CYP2C8 in multiple myeloma: a genome-wide single nucleotide polymorphism analysis

Blood ◽  
2008 ◽  
Vol 112 (7) ◽  
pp. 2709-2712 ◽  
Author(s):  
Maria E. Sarasquete ◽  
Ramon García-Sanz ◽  
Luis Marín ◽  
Miguel Alcoceba ◽  
Maria C. Chillón ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Cytochrome P450 ◽  
Genome Wide Association Study ◽  
Osteonecrosis Of The Jaw ◽  
Bisphosphonate Therapy ◽  
Polymorphism Analysis ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Genome Wide ◽  
A Genome

Abstract We have explored the potential role of genetics in the development of osteonecrosis of the jaw (ONJ) in multiple myeloma (MM) patients under bisphosphonate therapy. A genome-wide association study was performed using 500 568 single nucleotide polymorphisms (SNPs) in 2 series of homogeneously treated MM patients, one with ONJ (22 MM cases) and another without ONJ (65 matched MM controls). Four SNPs (rs1934951, rs1934980, rs1341162, and rs17110453) mapped within the cytochrome P450-2C gene (CYP2C8) showed a different distribution between cases and controls with statistically significant differences (P = 1.07 × 10−6, P = 4.231 × 10−6, P = 6.22 × 10−6, and P = 2.15 × 10−6, respectively). SNP rs1934951 was significantly associated with a higher risk of ONJ development even after Bonferroni correction (P corrected value = .02). Genotyping results displayed an overrepresentation of the T allele in cases compared with controls (48% vs 12%). Thus, individuals homozygous for the T allele had an increased likelihood of developing ONJ (odds ratio 12.75, 95% confidence interval 3.7-43.5).

scholarly journals Haplotypes within tandemly duplicated candidate genes at BnaA9.MRP5 modulate phytate concentration in canola (Brassica napus L.)

2021 ◽  
Author(s):  
Haijiang Liu ◽  
xiaojuan Li ◽  
Qianwen Zhang ◽  
pan yuan ◽  
Lei Liu ◽  
...  
Keyword(s):  
Candidate Genes ◽  
Oilseed Rape ◽  
Genome Wide Association Study ◽  
Mineral Elements ◽  
Nucleotide Polymorphisms ◽  
Brassica Napus L ◽  
Single Nucleotide ◽  
Genome Wide ◽  
A Genome ◽  
Phytate Content

Phytate is the storage form of phosphorus in angiosperm seeds and plays vitally important roles during seed development. However, in crop plants phytate decreases bioavailability of seed-sourced mineral elements for humans, livestock and poultry, and contributes to phosphate-related water pollution. However, there is little knowledge about this trait in oilseed rape B. napus (oilseed rape). Here, a panel of 505 diverse B. napus accessions was screened in a genome-wide association study (GWAS) using 3.28 x 106 single nucleotide polymorphisms (SNPs). This identified 119 SNPs significantly associated with phytate concentration (PA_Conc) and phytate content (PA_Cont) and six candidate genes were identified. Of these, BnaA9.MRP5 represented the candidate gene for the significant SNP chrA09_5198034 (27kb) for both PA_Cont and PA_Conc. Transcription of BnaA9.MRP5 in a low -phytate variety (LPA20) was significantly elevated compared with a high -phytate variety (HPA972). Association and haplotype analysis indicated that inbred lines carrying specific SNP haplotypes within BnaA9.MRP5 were associated with high- and low-phytate phenotypes. No significant differences in seed germination and seed yield were detected between low and high phytate cultivars examined. Candidate genes, favorable haplotypes and the low phytate varieties identified in this study will be useful for low-phytate breeding of B. napus.

Lifestyle factors and genetic variants on two biological age measures: evidence from 94,443 Taiwan Biobank participants

2021 ◽  
Author(s):  
Wan-Yu Lin
Keyword(s):  
Genetic Variants ◽  
Genome Wide Association Study ◽  
Lifestyle Factors ◽  
Biological Age ◽  
Biological Aging ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Genome Wide ◽  
A Genome ◽  
The Uk

Abstract Background Biological age (BA) can be estimated by phenotypes and is useful for predicting lifespan and healthspan. Levine et al. proposed a PhenoAge and a BioAge to measure BA. Although there have been studies investigating the genetic predisposition to BA acceleration in Europeans, little has been known regarding this topic in Asians. Methods I here estimated PhenoAgeAccel (age-adjusted PhenoAge) and BioAgeAccel (age-adjusted BioAge) of 94,443 Taiwan Biobank (TWB) participants, wherein 25,460 TWB1 subjects formed a discovery cohort and 68,983 TWB2 individuals constructed a replication cohort. Lifestyle factors and genetic variants associated with PhenoAgeAccel and BioAgeAccel were investigated through regression analysis and a genome-wide association study (GWAS). Results A unit (kg/m 2) increase of BMI was associated with a 0.177-year PhenoAgeAccel (95% C.I. = 0.163~0.191, p = 6.0×) and 0.171-year BioAgeAccel (95% C.I. = 0.165~0.177, p = 0). Smokers on average had a 1.134-year PhenoAgeAccel (95% C.I. = 0.966~1.303, p = 1.3×) compared with non-smokers. Drinkers on average had a 0.640-year PhenoAgeAccel (95% C.I. = 0.433~0.847, p = 1.3×) and 0.193-year BioAgeAccel (95% C.I. = 0.107~0.279, p = 1.1×) relative to non-drinkers. A total of 11 and 4 single-nucleotide polymorphisms (SNPs) were associated with PhenoAgeAccel and BioAgeAccel (p<5× in both TWB1 and TWB2), respectively. Conclusions A PhenoAgeAccel-associated SNP (rs1260326 in GCKR) and two BioAgeAccel-associated SNPs (rs7412 in APOE; rs16998073 near FGF5) were consistent with the finding from the UK Biobank. The lifestyle analysis shows that prevention from obesity, cigarette smoking, and alcohol consumption is associated with a slower rate of biological aging.

scholarly journals Association of GATA3 Polymorphisms With Minimal Residual Disease and Relapse Risk in Childhood Acute Lymphoblastic Leukemia

2020 ◽  
Author(s):  
Hui Zhang ◽  
Anthony Pak-Yin Liu ◽  
Meenakshi Devidas ◽  
Shawn H R Lee ◽  
Xueyuan Cao ◽  
...  
Keyword(s):  
Genome Wide Association Study ◽  
Validation Cohort ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Dichotomous Variable ◽  
Genome Wide ◽  
A Genome ◽  
Minimal Residual

Abstract Background Minimal residual disease (MRD) after induction therapy is one of the strongest prognostic factors in childhood acute lymphoblastic leukemia (ALL), and MRD-directed treatment intensification improves survival. Little is known about the effects of inherited genetic variants on interpatient variability in MRD. Methods A genome-wide association study was performed on 2597 children on the Children’s Oncology Group AALL0232 trial for high-risk B-cell ALL. Association between genotype and end-of-induction MRD levels was evaluated for 863 370 single nucleotide polymorphisms (SNPs), adjusting for genetic ancestry and treatment strata. Top variants were further evaluated in a validation cohort of 491 patients from the Children’s Oncology Group P9905 and 6 ALL trials. The independent prognostic value of single nucleotide polymorphisms was determined in multivariable analyses. All statistical tests were 2-sided. Results In the discovery genome-wide association study, we identified a genome-wide significant association at the GATA3 locus (rs3824662, odds ratio [OR] = 1.58, 95% confidence interval [CI] = 1.35 to 1.84; P = 1.15 × 10-8 as a dichotomous variable). This association was replicated in the validation cohort (P = .003, MRD as a dichotomous variable). The rs3824662 risk allele independently predicted ALL relapse after adjusting for age, white blood cell count, and leukemia DNA index (P = .04 and .007 in the discovery and validation cohort, respectively) and remained prognostic when the analyses were restricted to MRD-negative patients (P = .04 and .03 for the discovery and validation cohorts, respectively). Conclusion Inherited GATA3 variant rs3824662 strongly influences ALL response to remission induction therapy and is associated with relapse. This work highlights the potential utility of germline variants in upfront risk stratification in ALL.

scholarly journals The Continuing Evolution of Community-Associated MRSA ST93-IV in Australia

2020 ◽  
Author(s):  
Stanley Pang ◽  
Denise A Daley ◽  
Shafi Sahibzada ◽  
Shakeel Mowlaboccus ◽  
Marc Stegger ◽  
...  
Keyword(s):  
Genome Wide Association Study ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Genetic Traits ◽  
Genome Wide ◽  
A Genome ◽  
High Prevalence ◽  
Northern Regions ◽  
Australian Community ◽  
Gwas Approach

Abstract BackgroundThe global emergence of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has seen the dominance of specific clones in different regions around the world with the PVL-positive ST93-IV as the predominant CA-MRSA clone in Australia. In this study we applied a genome-wide association study (GWAS) approach on a collection of Australian ST93-IV MRSA genomes to identify genetic traits that may have assisted the ongoing transmission of ST93-IV in Australia. We also compared the genomes of ST93-IV bacteraemia and non-bacteraemia isolates to identify potential virulence factors associated with bacteraemia.ResultsBased on single nucleotide polymorphism phylogenetics we identified two distinct ST93-IV clades circulating concurrently in Australia. One of the clades contained isolates primarily isolated in the northern regions of Australia whilst isolates in the second clade were distributed across the country. Analyses of the ST93-IV genome plasticity over a 15-year period (2002-2017) revealed an observed gain in accessory genes amongst the clone’s population. The GWAS analysis on the bacteraemia identified two genes that have also previously been associated to this kind of infection. ConclusionsThe emergence of a ST93-IV clade containing additional virulence genes may explain the high prevalence of ST93-IV infections amongst the indigenous population living in the northern regions of Australia. In summary, this study has shown ST93-IV is evolving with multiple additional genes possibly contributing to its dominance in the Australian community.

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