Genome Wide Association Study (GWAS) of cognitive impairment after blood or marrow transplantation (BMT) for hematologic malignancy.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 1536-1536
Author(s):  
Noha Sharafeldin ◽  
Purnima Singh ◽  
Alysia Bosworth ◽  
Akinyemi I Ojesina ◽  
Jianqing Zhang ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Cognitive Impairment ◽  
Genome Wide Association Study ◽  
Risk Allele ◽  
Hematologic Malignancy ◽  
Snp Array ◽  
Summary Score ◽  
Allogeneic Bmt ◽  
Genome Wide ◽  
A Genome

1536 Background: Cognitive impairment is prevalent in hematologic malignancy patients treated with BMT (autologous: 18.7%; allogeneic: 35.7%; Sharafeldin JCO; 2018). Given the inter-individual variability in risk of cognitive impairment in this population, we investigated the role of genetic susceptibility using a genome-wide single nucleotide polymorphism (SNP) array platform to identify novel genetic associations. Methods: Discovery: Cognitive function was assessed objectively in 239 adult BMT recipients at pre-specified timepoints: pre-BMT and at 6 mo, 1y, 2y, and 3y post-BMT. A global deficit score (GDS - a summary score of 14 standardized neuropsychological tests) was computed for each patient; a higher score indicated greater cognitive impairment. SNPs passing standard quality control filters ( > 1.4M) were used for analysis. Linear mixed effects models used GDS as the outcome, adjusted for age, sex, BMT type, baseline cognitive reserve, and the first four principal components. We used additive, codominant, and genotype models and an adjusted genome-wide significance threshold of 1.25 x 10−8. Replication: An independent cohort of 544 BMT survivors (192 cases with self-endorsed cognitive problems and 352 controls without) was used for replication. Results: Discovery: Median age at BMT was 51.3y; primary diagnoses: 47% leukemia, 32% lymphoma, 21% multiple myeloma; 57% males; 69% non-Hispanic whites: 50% allogeneic BMT, median GDS score = 0.22 (range 0-2). Forty-four SNPs were significantly associated with increased GDS (additive model: 3 SNPs; codominant model: 20 SNPs; genotype model: 21 SNPs). Estimates ranged from increase in GDS score by 0.28 points for each additional copy of risk allele, p = 1.07 x 10−8 to increase in GDS score by 1.82 points for two copies of risk allele, p = 2.3 x 10−11. Replication: Median age at BMT was 44y; primary diagnoses: 32% leukemia, 49% lymphoma, 19% multiple myeloma; 54% males; 80% non-Hispanic whites: 34% allogeneic BMT. Three SNPs were successfully replicated: rs116334183 resides within lncRNA-SEMA6D-2, which facilitates neuronal migration; rs13286152 86kb downstream of TLE-1, which promotes neuronal survival; and rs12486041 0.36Mb downstream from lncRNA-SPTSSB-1, which regulates sphingolipid production in neuronal axons and 0.36Mb upstream from TOMM22P6 linked to neural repair. Conclusions: In this first GWAS of cognitive impairment post-BMT, we identify 3 SNPs with plausible links to genes implicated in neuronal integrity. Functional studies are currently underway.

scholarly journals Genome-Wide Analyses Identifies Known and New Markers Responsible of Chicken Plumage Color

Animals ◽  
2020 ◽  
Vol 10 (3) ◽  
pp. 493
Author(s):  
Salvatore Mastrangelo ◽  
Filippo Cendron ◽  
Gianluca Sottile ◽  
Giovanni Niero ◽  
Baldassare Portolano ◽  
...  
Keyword(s):  
Genome Wide Association Study ◽  
Snp Array ◽  
Fixation Index ◽  
Phenotypic Traits ◽  
Plumage Color ◽  
Phenotypic Marker ◽  
Genome Wide ◽  
A Genome ◽  
The Difference ◽  
Genomic Regions

Through the development of the high-throughput genotyping arrays, molecular markers and genes related to phenotypic traits have been identified in livestock species. In poultry, plumage color is an important qualitative trait that can be used as phenotypic marker for breed identification. In order to assess sources of genetic variation related to the Polverara chicken breed plumage colour (black vs. white), we carried out a genome-wide association study (GWAS) and a genome-wide fixation index (FST) scan to uncover the genomic regions involved. A total of 37 animals (17 white and 20 black) were genotyped with the Affymetrix 600 K Chicken single nucleotide polymorphism (SNP) Array. The combination of results from GWAS and FST revealed a total of 40 significant markers distributed on GGA 01, 03, 08, 12 and 21, and located within or near known genes. In addition to the well-known TYR, other candidate genes have been identified in this study, such as GRM5, RAB38 and NOTCH2. All these genes could explain the difference between the two Polverara breeds. Therefore, this study provides the basis for further investigation of the genetic mechanisms involved in plumage color in chicken.

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 Genome-wide association study identifies loci and candidate genes for internal organ weights in Simmental beef cattle

2018 ◽  
Vol 50 (7) ◽  
pp. 523-531 ◽  
Author(s):  
Bingxing An ◽  
Jiangwei Xia ◽  
Tianpeng Chang ◽  
Xiaoqiao Wang ◽  
Jian Miao ◽  
...  
Keyword(s):  
Beef Cattle ◽  
Association Study ◽  
Genome Wide Association Study ◽  
Snp Array ◽  
Genome Wide Association ◽  
Heart Weight ◽  
Spleen Weight ◽  
Internal Organs ◽  
Genome Wide ◽  
A Genome

Cattle internal organs as accessible raw materials have a long history of being widely used in beef processing, feed and pharmaceutical industry. These traits not only are of economic interest to breeders, but they are intrinsically linked to many valuable traits, such as growth, health, and productivity. Using the Illumina Bovine HD 770K SNP array, we performed a genome-wide association study for heart weight, liver weight, spleen weight, lung weight, and kidney weight in 1,217 Simmental cattle. In our research, 38 significant single nucleotide polymorphisms (SNPs) ( P < 1.49 × 10−6) were identified for five internal organ weight traits. These SNPs are within or near 13 genes, and some of them have been reported previously, including NDUFAF4, LCORL, BT.94996, SLIT2, FAM184B, LAP3, BBS12, MECOM, CD300LF, HSD17B3, TLR4, MXI1, and MB21D2. In addition, we detected four haplotype blocks on BTA6 containing 18 significant SNPs associated with spleen weight. Our results offer worthy insights into understanding the genetic mechanisms of internal organs' development, with potential application in breeding programs of Simmental beef cattle.

scholarly journals Genome-Wide Association Study of Susceptibility Loci for T-Cell Acute Lymphoblastic Leukemia in Children

2019 ◽  
Vol 111 (12) ◽  
pp. 1350-1357 ◽  
Author(s):  
Maoxiang Qian ◽  
Xujie Zhao ◽  
Meenakshi Devidas ◽  
Wenjian Yang ◽  
Yoshihiro Gocho ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Association Study ◽  
Genome Wide Association Study ◽  
Risk Allele ◽  
Lymphoblastic Leukemia ◽  
Genome Wide Association ◽  
Luciferase Assay ◽  
Susceptibility Loci ◽  
Genome Wide ◽  
A Genome

Abstract Background Acute lymphoblastic leukemia (ALL) is the most common cancer in children and can arise in B or T lymphoid lineages. Although risk loci have been identified for B-ALL, the inherited basis of T-ALL is mostly unknown, with a particular paucity of genome-wide investigation of susceptibility variants in large patient cohorts. Methods We performed a genome-wide association study (GWAS) in 1191 children with T-ALL and 12 178 controls, with independent replication using 117 cases and 5518 controls. The associations were tested using an additive logistic regression model. Top risk variants were tested for effects on enhancer activity using luciferase assay. All statistical tests were two sided. Results A novel risk locus in the USP7 gene (rs74010351, odds ratio [OR] = 1.44, 95% confidence interval [CI] = 1.27 to 1.65, P = 4.51 × 10–8) reached genome-wide significance in the discovery cohort, with independent validation (OR = 1.51, 95% CI = 1.03 to 2.22, P = .04). The USP7 risk allele was overrepresented in individuals of African descent, thus contributing to the higher incidence of T-ALL in this race/ethnic group. Genetic changes in USP7 (germline variants or somatic mutations) were observed in 56.4% of T-ALL with TAL1 overexpression, statistically significantly higher than in any other subtypes. Functional analyses suggested this T-ALL risk allele is located in a putative cis-regulatory DNA element with negative effects on USP7 transcription. Finally, comprehensive comparison of 14 susceptibility loci in T- vs B-ALL pointed to distinctive etiology of these leukemias. Conclusions These findings indicate strong associations between inherited genetic variation and T-ALL susceptibility in children and shed new light on the molecular etiology of ALL, particularly commonalities and differences in the biology of the two major subtypes (B- vs T-ALL).

scholarly journals Transcriptomic and Genome-wide Association Study Reveal Long Noncoding RNAs Responding to Nitrogen Deficiency in Maize

2020 ◽  
Author(s):  
PENG MA ◽  
Xiao Zhang ◽  
Bowen Luo ◽  
Zhen Chen ◽  
Xuan He ◽  
...  
Keyword(s):  
Association Study ◽  
Genome Wide Association Study ◽  
Nitrogen Deficiency ◽  
Snp Array ◽  
Noncoding Rnas ◽  
Long Noncoding Rnas ◽  
Genome Wide Association ◽  
Rna Seq ◽  
Genome Wide ◽  
A Genome

Abstract Background: Long noncoding RNAs (lncRNAs) play important roles in essential biological processes. However, our understanding of lncRNAs as competing endogenous RNAs (ceRNAs) and their responses to nitrogen stress is still limited.Results: Here, we surveyed the lncRNAs and miRNAs in maize inbred line P178 leaves and roots at the seedling stage under high-nitrogen and low-nitrogen conditions using lncRNA-Seq and small RNA-Seq. A total of 894 differentially expressed lncRNAs and 38 different miRNAs were identified. Co-expression analysis found two lncRNAs and four lncRNA-targets could competitively combine with ZmmiR159 and ZmmiR164, respectively. To dissect the genetic regulatory by which lncRNAs might enable adaptation to limited nitrogen availability. An association mapping panel containing a high-density single–nucleotide polymorphism (SNP) array (56,110 SNPs) combined with variable LN resistance-related phenotypes obtained from hydroponics was used for a genome-wide association study (GWAS). By combining GWAS and RNA-Seq, 170 differently expressed lncRNAs within the range of significant markers were screened. Moreover, 40 consistently LN-responsive genes including those involved in glutamine biosynthesis and nitrogen acquisition in root were identified. Transient expression assays in Nicotiana benthamiana demonstrated LNC_002923 could inhabit ZmmiR159-guided cleavage of Zm00001d015521. Conclusions: These lncRNAs containing trait-associated significant SNPs could consider to be related to root development and nutrient utilization. Taken together, the results of our study can provide new insights into the potential regulatory roles of lncRNAs in response to LN stress, and give valuable information for further screening of candidates as well as the improvement of maize regarding LN-responsive resistance.

scholarly journals Japan COVID-19 Task Force: a nation-wide consortium to elucidate host genetics of COVID-19 pandemic in Japan

2021 ◽  
Author(s):  
Ho Namkoong ◽  
Ryuya Edahiro ◽  
Koichi Fukunaga ◽  
Yuya Shirai ◽  
Kyuto Sonehara ◽  
...  
Keyword(s):  
Genome Wide Association Study ◽  
Risk Allele ◽  
Task Force ◽  
European Population ◽  
P Value ◽  
Host Genetics ◽  
Risk Variants ◽  
Genome Wide ◽  
A Genome ◽  
The Face

To elucidate the host genetic loci affecting severity of SARS-CoV-2 infection, or Coronavirus disease 2019 (COVID-19), is an emerging issue in the face of the current devastating pandemic. Here, we report a genome-wide association study (GWAS) of COVID-19 in a Japanese population led by the Japan COVID-19 Task Force, as one of the initial discovery GWAS studies performed on a non-European population. Enrolling a total of 2,393 cases and 3,289 controls, we not only replicated previously reported COVID-19 risk variants (e.g., LZTFL1, FOXP4, ABO, and IFNAR2), but also found a variant on 5p35 (rs60200309-A at DOCK2) that was significantly associated with severe COVID-19 in younger (<65 years of age) patients with a genome-wide significant p-value of 1.2 × 10-8 (odds ratio = 2.01, 95% confidence interval = 1.58-2.55). This risk allele was prevalent in East Asians, including Japanese (minor allele frequency [MAF] = 0.097), but rarely found in Europeans. Cross-population Mendelian randomization analysis made a causal inference of a number of complex human traits on COVID-19. In particular, obesity had a significant impact on severe COVID-19. The presence of the population-specific risk allele underscores the need of non-European studies of COVID-19 host genetics.

Genome-Wide association study identifies new elements on the genetic basis of quality-related traits in wheat across multiple environments

2020 ◽  
Author(s):  
Zhien Pu ◽  
Xueling Ye ◽  
Yang Li ◽  
Zehou Liu ◽  
Bingxin Shi ◽  
...  
Keyword(s):  
Association Study ◽  
Complex Traits ◽  
Genome Wide Association Study ◽  
Snp Array ◽  
Mixed Linear Model ◽  
Genome Wide Association ◽  
Phenotypic Analysis ◽  
Genome Wide ◽  
A Genome ◽  
Genomic Regions

Abstract Backgrounds: Grain protein concentration (GPC), grain starch concentration (GSC), and wet gluten concentration (WGC) are complex traits that determine nutrient concentration, end-use quality, and yield in wheat. To identify the elite and stable loci or genomic regions conferring high GPC, GSC, and WGC, a genome-wide association study (GWAS) based on a mixed linear model (MLM) was performed using 55K single nucleotide polymorphism (SNP) array in a panel of 236 wheat accessions, including 160 commercial varieties and 76 landraces, derived from Sichuan Province, China. The panel was evaluated for GPC, GSC, and WGC at four different fields. Results: Phenotypic analysis showed variation in GPC, GSC, and WGC among the different genotypes and environments. GWAS identified 12 quantitative trait loci (QTL) (-log10(P) > 2.5) associated with these three quality traits in at least two environments and located on chromosomes 1B, 1D, 2A, 2B, 2D, 3B, 3D, 5D, and 7D; the phenotypic variation explained (PVE) by these QTL ranged from 4.2% to 10.7%. Among these, three, seven, and two QTL are associated with GPC, GSC, and WGC, respectively; five QTL (QGsc.sicau-1BL, QGsc.sicau-1DS, QGsc.sicau-2DL.1, QGsc.sicau-2DL.2, QWgc.sicau-5DL) were defined potentially novel Compared with the previously reported QTLs/genes by linkage or association mapping, 5 QTLs (QGsc.sicau-1BL, QGsc.sicau-1DS, QGsc.sicau-2DL.1, QGsc.sicau-2DL.2, QWgc.sicau-5DL) were potentially novel. Furthermore, 21 presumptive candidate genes, which are involved in the metabolism or transportation of all kinds of carbohydrates, photosynthesis, programmed cell death, the balance of abscisic acid and ethylene, within these potentially novel genomic regions were predicted. Conclusions: This study provided new genetic resources and valuable genetic information of nutritional quality to broaden the genetic background and laid the molecular foundation for marker-assisted selection in wheat quality breeding.

scholarly journals Transcriptomic and genome-wide association study reveal long noncoding RNAs responding to nitrogen deficiency in maize

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Peng Ma ◽  
Xiao Zhang ◽  
Bowen Luo ◽  
Zhen Chen ◽  
Xuan He ◽  
...  
Keyword(s):  
Association Study ◽  
Genome Wide Association Study ◽  
Nitrogen Deficiency ◽  
Snp Array ◽  
Noncoding Rnas ◽  
Long Noncoding Rnas ◽  
Genome Wide Association ◽  
Rna Seq ◽  
Genome Wide ◽  
A Genome

Abstract Background Long noncoding RNAs (lncRNAs) play important roles in essential biological processes. However, our understanding of lncRNAs as competing endogenous RNAs (ceRNAs) and their responses to nitrogen stress is still limited. Results Here, we surveyed the lncRNAs and miRNAs in maize inbred line P178 leaves and roots at the seedling stage under high-nitrogen (HN) and low-nitrogen (LN) conditions using lncRNA-Seq and small RNA-Seq. A total of 894 differentially expressed lncRNAs and 38 different miRNAs were identified. Co-expression analysis found that two lncRNAs and four lncRNA-targets could competitively combine with ZmmiR159 and ZmmiR164, respectively. To dissect the genetic regulatory by which lncRNAs might enable adaptation to limited nitrogen availability, an association mapping panel containing a high-density single–nucleotide polymorphism (SNP) array (56,110 SNPs) combined with variable LN tolerant-related phenotypes obtained from hydroponics was used for a genome-wide association study (GWAS). By combining GWAS and RNA-Seq, 170 differently expressed lncRNAs within the range of significant markers were screened. Moreover, 40 consistently LN-responsive genes including those involved in glutamine biosynthesis and nitrogen acquisition in root were identified. Transient expression assays in Nicotiana benthamiana demonstrated that LNC_002923 could inhabit ZmmiR159-guided cleavage of Zm00001d015521. Conclusions These lncRNAs containing trait-associated significant SNPs could consider to be related to root development and nutrient utilization. Taken together, the results of our study can provide new insights into the potential regulatory roles of lncRNAs in response to LN stress, and give valuable information for further screening of candidates as well as the improvement of maize resistance to LN stress.

scholarly journals LRRTM4 and PCSK5 Genetic Polymorphisms as Markers for Cognitive Impairment in A Hypotensive Aging Population: A Genome-Wide Association Study in Taiwan

2019 ◽  
Vol 8 (8) ◽  
pp. 1124 ◽  
Author(s):  
Yi-Chun Chen ◽  
Yu-Li Liu ◽  
Shih-Jen Tsai ◽  
Po-Hsiu Kuo ◽  
Shih-Sin Huang ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Sex Education ◽  
Healthy Aging ◽  
Genome Wide Association Study ◽  
Population Based ◽  
Cognitive Outcomes ◽  
Nucleotide Polymorphisms ◽  
Genome Wide ◽  
A Genome ◽  
Minor Alleles

Hypotension can affect cerebral perfusion and worsen cognitive outcomes. The prevalence of low blood pressure (BP) rises with increasing age. To our knowledge, no study has examined the genetic biomarkers for hypotension-related cognitive impairment (CI) yet. Utilizing the population-based genome-wide study of the Taiwan Biobank containing the data of 2533 healthy aging subjects, we found after adjustments for age, sex, education years, and principal components at a suggestive level of 1 × 10−5 that minor alleles of leucine rich repeat transmembrane neuronal 4 (LRRTM4) (rs13388459, rs1075716, rs62171995, rs17406146, rs2077823, and rs62170897), proprotein convertase subtilisin/kexin type 5 (PCSK5) (rs10521467), and the intergenic variation rs117129097 (the nearby gene: TMEM132C) are risk factors for CI in hypotensive subjects. Except for rs117129097, these single nucleotide polymorphisms (SNPs) were not markers per se for CI or for BP regulation. However, we found a suggestive interaction effect between each of the eight SNPs and hypotension on CI risk. In the hypotensive participants, those carrying minor alleles were associated with a higher incidence of CI in an additive manner than were those carrying major alleles (2 × 10−4 to 9 × 10−7). Intensive BP lowering in elderly patients carrying a minor allele of the eight identified SNPs should raise cautions to prevent a potential treatment-induced neurodegeneration.

scholarly journals Genome-Wide Association Mapping of Resistance to Fusarium Head Blight Spread and Deoxynivalenol Accumulation in Chinese Elite Wheat Germplasm

2019 ◽  
Vol 109 (7) ◽  
pp. 1208-1216 ◽  
Author(s):  
Lei Wu ◽  
Yu Zhang ◽  
Yi He ◽  
Peng Jiang ◽  
Xu Zhang ◽  
...  
Keyword(s):  
Fusarium Head Blight ◽  
Genome Wide Association Study ◽  
Snp Array ◽  
Snp Markers ◽  
Genome Wide Association ◽  
Head Blight ◽  
Sources Of Resistance ◽  
Wheat Germplasm ◽  
Genome Wide ◽  
A Genome

Improving resistance to Fusarium head blight (FHB) in wheat is crucial in the integrated management of the disease and prevention of deoxynivalenol (DON) contamination in grains. To identify novel sources of resistance, a genome-wide association study (GWAS) was performed using a panel of 213 accessions of elite wheat germplasm of China. The panel was evaluated for FHB severity in four environments and DON content in grains in two environments. High correlations across environments and high heritability were observed for FHB severity and DON content in grains. The panel was also genotyped with the 90K Illumina iSelect single nucleotide polymorphism (SNP) array and 11,461 SNP markers were obtained. The GWAS revealed a total of six and three loci significantly associated with resistance to fungal spread and DON accumulation in at least two environments, respectively. QFHB-2BL.1 tagged by IWB52433 and QFHB-3A tagged by IWB50548 were responsible for resistance to both fungal spread and DON accumulation. In summary, this study provided an overview of FHB resistance resources in elite Chinese wheat germplasm and identified novel resistance loci that could be used for wheat improvement.

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