scholarly journals Identifying genetic modifiers of age-associated penetrance in X-linked dystonia-parkinsonism

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Björn-Hergen Laabs ◽  
Christine Klein ◽  
Jelena Pozojevic ◽  
Aloysius Domingo ◽  
Norbert Brüggemann ◽  
...  
Keyword(s):  
Genome Wide Association Study ◽  
Neurodegenerative Disorder ◽  
Age At Onset ◽  
Disease Onset ◽  
Nucleotide Polymorphisms ◽  
Genetic Modifiers ◽  
Dna Mismatch ◽  
Hexanucleotide Repeat ◽  
Genome Wide ◽  
A Genome

AbstractX-linked dystonia-parkinsonism is a neurodegenerative disorder caused by a founder retrotransposon insertion, in which a polymorphic hexanucleotide repeat accounts for ~50% of age at onset variability. Employing a genome-wide association study to identify additional factors modifying age at onset, we establish that three independent loci are significantly associated with age at onset (p < 5 × 10−8). The lead single nucleotide polymorphisms collectively account for 25.6% of the remaining variance not explained by the hexanucleotide repeat and 13.0% of the overall variance in age at onset in X-linked dystonia-parkinsonism with the protective alleles delaying disease onset by seven years. These regions harbor or lie adjacent to MSH3 and PMS2, the genes that were recently implicated in modifying age at onset in Huntington’s disease, likely through a common pathway influencing repeat instability. Our work indicates the existence of three modifiers of age at onset in X-linked dystonia-parkinsonism that likely affect the DNA mismatch repair pathway.

scholarly journals Genome-Wide Association Study (GWAS) for Examining the Genomics Controlling Prickle Production in Red Raspberry (Rubus idaeus L.)

Agronomy ◽  
2020 ◽  
Vol 11 (1) ◽  
pp. 27
Author(s):  
Archana Khadgi ◽  
Courtney A. Weber
Keyword(s):  
Association Study ◽  
Genome Wide Association Study ◽  
Genomic Region ◽  
Rubus Idaeus ◽  
Genome Wide Association ◽  
Nucleotide Polymorphisms ◽  
Red Raspberry ◽  
Genome Wide ◽  
A Genome ◽  
Genotype By Sequencing

Red raspberry (Rubus idaeus L.) is an expanding high-value berry crop worldwide. The presence of prickles, outgrowths of epidermal tissues lacking vasculature, on the canes, petioles, and undersides of leaves complicates both field management and harvest. The utilization of cultivars with fewer prickles or prickle-free canes simplifies production. A previously generated population segregating for prickles utilizing the s locus between the prickle-free cultivar Joan J (ss) and the prickled cultivar Caroline (Ss) was analyzed to identify the genomic region associated with prickle development in red raspberry. Genotype by sequencing (GBS) was combined with a genome-wide association study (GWAS) using fixed and random model circulating probability unification (FarmCPU) to analyze 8474 single nucleotide polymorphisms (SNPs) and identify significant markers associated with the prickle-free trait. A total of four SNPs were identified on chromosome 4 that were associated with the phenotype and were located near or in annotated genes. This study demonstrates how association genetics can be used to decipher the genetic control of important horticultural traits in Rubus, and provides valuable information about the genomic region and potential genes underlying the prickle-free trait.

scholarly journals Genome-Wide Association Analysis of Growth Curve Parameters in Chinese Simmental Beef Cattle

Animals ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 192
Author(s):  
Xinghai Duan ◽  
Bingxing An ◽  
Lili Du ◽  
Tianpeng Chang ◽  
Mang Liang ◽  
...  
Keyword(s):  
Beef Cattle ◽  
Candidate Genes ◽  
Growth Curve ◽  
Growth And Development ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Coefficient Of Determination ◽  
Nucleotide Polymorphisms ◽  
Genome Wide ◽  
A Genome

The objective of the present study was to perform a genome-wide association study (GWAS) for growth curve parameters using nonlinear models that fit original weight–age records. In this study, data from 808 Chinese Simmental beef cattle that were weighed at 0, 6, 12, and 18 months of age were used to fit the growth curve. The Gompertz model showed the highest coefficient of determination (R2 = 0.954). The parameters’ mature body weight (A), time-scale parameter (b), and maturity rate (K) were treated as phenotypes for single-trait GWAS and multi-trait GWAS. In total, 9, 49, and 7 significant SNPs associated with A, b, and K were identified by single-trait GWAS; 22 significant single nucleotide polymorphisms (SNPs) were identified by multi-trait GWAS. Among them, we observed several candidate genes, including PLIN3, KCNS3, TMCO1, PRKAG3, ANGPTL2, IGF-1, SHISA9, and STK3, which were previously reported to associate with growth and development. Further research for these candidate genes may be useful for exploring the full genetic architecture underlying growth and development traits in livestock.

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 Mapping for Heat and Drought Adaptive Traits in Pea

Genes ◽  
2021 ◽  
Vol 12 (12) ◽  
pp. 1897
Author(s):  
Endale G. Tafesse ◽  
Krishna K. Gali ◽  
V. B. Reddy Lachagari ◽  
Rosalind Bueckert ◽  
Thomas D. Warkentin
Keyword(s):  
Association Mapping ◽  
Candidate Genes ◽  
Vegetation Index ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Nucleotide Polymorphisms ◽  
Adaptive Traits ◽  
Flowering Duration ◽  
Genome Wide ◽  
A Genome

Heat and drought, individually or in combination, limit pea productivity. Fortunately, substantial genetic diversity exists in pea germplasm for traits related to abiotic stress resistance. Understanding the genetic basis of resistance could accelerate the development of stress-adaptive cultivars. We conducted a genome-wide association study (GWAS) in pea on six stress-adaptive traits with the aim to detect the genetic regions controlling these traits. One hundred and thirty-five genetically diverse pea accessions were phenotyped in field studies across three or five environments under stress and control conditions. To determine marker trait associations (MTAs), a total of 16,877 valuable single nucleotide polymorphisms (SNPs) were used in association analysis. Association mapping detected 15 MTAs that were significantly (p ≤ 0.0005) associated with the six stress-adaptive traits averaged across all environments and consistent in multiple individual environments. The identified MTAs were four for lamina wax, three for petiole wax, three for stem thickness, two for the flowering duration, one for the normalized difference vegetation index (NDVI), and two for the normalized pigment and chlorophyll index (NPCI). Sixteen candidate genes were identified within a 15 kb distance from either side of the markers. The detected MTAs and candidate genes have prospective use towards selecting stress-hardy pea cultivars in marker-assisted selection.

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&lt;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.

Abstract 4437: Genome-Wide Association Study for the Response to Antihypertensive Medication: HOMED-BP-GENE Study

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Tomohiro Katsuya ◽  
Kei Asayama ◽  
Ryusuke Inoue ◽  
Ken Sugimoto ◽  
Takayoshi Ohkubo ◽  
...  
Keyword(s):  
Association Study ◽  
Antihypertensive Medication ◽  
Genome Wide Association Study ◽  
Early Morning ◽  
Home Blood Pressure ◽  
Genome Wide Association ◽  
Nucleotide Polymorphisms ◽  
Genome Wide ◽  
A Genome ◽  
Drug Responsiveness

AAntihypertensive therapy is a powerful approach to prevent the cardiovascular disease. However, the responsiveness of the therapy is highly individual due to the variability of genetic or environmental factors. To elucidate the genetic background underlying antihypertensive drug responsiveness, we carried out a genome-wide association study (GWAS). The subjects studied were recruited from the participants of HOMED-BP study (UMIN Registered ID C000000137, http://www.cpt.med.tohoku.ac.jp/HOMED-BP/) after obtaining the informed consent for the genetic analysis. After DNA extraction from peripheral blood, about half million single nucleotide polymorphisms (SNPs) were examined using GeneChip Genome-Wide Human SNP5.0 Array (Affymetrix). Home blood pressure (HBP) was measured every day within 1 hour after wake-up and before going to bed using HEM747-IC-N (Omron). The study protocol was approved by the ethical committee of Osaka University. SNP5.0 Array analysis was demonstrated for 300 participants. Antihypertensive therapy for 4weeks decreased their average HBP from 149.9/88.8mmHg to 137.7/82.2mmHg in early morning and 142.6/82.3mmHg to 129.1/74.7mmHg before going to bed. We excluded the SNPs data that showed low call rate, lack of Hardy-Weinberg’s equilibrium and minor allele frequency less than 0.05. Eight SNPs were significantly (p<0.001) associated with mean HBP reduction both in the early morning and at bedtime. Nine SNPs were more significantly (p<0.0001) associated with morning HBP reduction and 3 SNPs were associated with bedtime HBP reduction. In conclusion, GWAS of antihypertensive medication revealed several candidate loci responsible for a month therapy with the difference between morning and evening.

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