A novel variant associated with HDL-C levels by modifying DAGLB expression levels: An annotation-based genome-wide association study

Abstract BackgroundRice rooting ability is a complex agronomical trait that displays heterosis and plays an important role in rice growth and production. Only a few quantitative trait loci (QTLs) have been identified by bi-parental population. More genes or QTLs are required to dissect the genetic architecture of rice rooting ability.ResultsTo characterize the genetic basis for rice rooting ability, we used a natural rice population, genotyped by a 90K single nucleotide polymorphism (SNP) array, to identify the loci associated with rooting-related traits through the genome-wide association study (GWAS). Population structure analysis divided the natural population into two subgroups: indica and japonica. We measured four traits for evaluating rice rooting ability, namely root growth ability (RGA), maximum root length (MRL), root length (RL), and root number (RN). Using the association study in three panels consisting of one for the full population, one for indica, and one for japonica, 24 SNPs associated with rooting ability-related traits were identified. Through comparison of the relative expression levels and DNA sequences between germplasm with extreme phenotypes, results showed that LOC_Os05g11810 had non-synonymous variations at the coding region, which may cause differences in root number, and that the expression levels of LOC_Os04g09900 and LOC_Os04g10060 are closely associated with root length variation.ConclusionsThrough evaluation of the rice rooting ability-related traits and the association mapping, we provided useful information for understanding the genetic basis of rice rooting ability and also identified some candidate genes and molecular markers for rice root breeding.

Download Full-text

Identification of a novel polymorphism associated with reduced clozapine concentration in schizophrenia patients—a genome-wide association study adjusting for smoking habits

Translational Psychiatry ◽

10.1038/s41398-020-00888-1 ◽

2020 ◽

Vol 10 (1) ◽

Cited By ~ 1

Author(s):

Robert Løvsletten Smith ◽

Kevin O’Connell ◽

Lavinia Athanasiu ◽

Srdjan Djurovic ◽

Marianne Kristiansen Kringen ◽

...

Keyword(s):

Serum Concentration ◽

Association Study ◽

Genome Wide Association Study ◽

Genome Wide Association ◽

Smoking Habits ◽

Serum Concentrations ◽

Genome Wide ◽

A Genome ◽

Increased Risk ◽

Novel Variant

Abstract Clozapine (CLZ) is the superior antipsychotic drug for treatment of schizophrenia, but exhibits an extensive interpatient pharmacokinetic variability. Here, we conducted a genome-wide association study (GWAS) of CLZ serum concentration adjusting for known smoking habits, which is a major nongenetic factor reducing CLZ levels. The study included 484 patients with 10,283 steady-state serum concentrations of CLZ and N-desmethylclozapine, prescribed dosing, co-medications and known smoking habits (n = 422; 9284 serum samples) from a therapeutic drug monitoring (TDM) service. The GWAS analyses were performed with and without smoking habits as covariate, where possible hits were assessed in relation to the target CLZ concentration range applied in the TDM service (300–2500 nmol/L). The smoking-independent analysis of N-desmethylclozapine serum concentration and the CLZ-to-N-desmethylclozapine ratio replicated the previously identified locus on chromosome 4. After adjusting for smoking habits in patients confirmed as ‘smokers’ (61%) or ‘nonsmokers’ (39%), a novel variant (rs28379954; minor T>C allele frequency 4.1%; 7.6% CT carriers in the population) within the gene encoding the nuclear factor 1 B-type (NFIB) was significantly associated with reduced CLZ serum concentration (p = 1.68 × 10−8, beta = −0.376; explained variance 7.63%). There was no significant association between rs28379954 and N-desmethylclozapine concentration in the GWAS analysis (p = 5.63 × 10−5). The fraction of CLZ TDM samples below 300 nmol/L was significantly higher in carriers vs. noncarriers of the rs28379954 minor C allele [12.0% (95% CI: 9.4–14.7) vs. 6.2% (95% CI: 5.7–6.8), p < 0.001]. We identified a novel variant in the NFIB gene associated with reduced CLZ levels and increased risk of subtherapeutic serum concentrations. This warrants testing of clinical relevance of screening for this gene variant, and also experimental studies to investigate the biological mechanisms of NFIB involvement in CLZ pharmacokinetics.

Download Full-text

P3-216: Identification of CIS variants associating with expression levels of 12 late-onset Alzheimer's disease (LOAD) candidate genes in a Genome-Wide Association Study (GWAS)

Alzheimer s & Dementia ◽

10.1016/j.jalz.2008.05.1783 ◽

2008 ◽

Vol 4 ◽

pp. T584-T584

Author(s):

Nilufer Ertekin-Taner ◽

Fanggeng Zou ◽

Minerva Carrasquillo ◽

Samuel Younkin ◽

Li Ma ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Association Study ◽

Candidate Genes ◽

Genome Wide Association Study ◽

Late Onset ◽

Genome Wide Association ◽

Expression Levels ◽

Genome Wide ◽

A Genome

Download Full-text

Genome‐wide association study identifying novel variant for fasting insulin and allelic heterogeneity in known glycemic loci in Chilean adolescents: The Santiago Longitudinal Study

Pediatric Obesity ◽

10.1111/ijpo.12765 ◽

2020 ◽

Author(s):

Victoria L Buchanan ◽

Yujie Wang ◽

Estela Blanco ◽

Mariaelisa Graff ◽

Cecilia Albala ◽

...

Keyword(s):

Longitudinal Study ◽

Association Study ◽

Genome Wide Association Study ◽

Genome Wide Association ◽

Allelic Heterogeneity ◽

Fasting Insulin ◽

Genome Wide ◽

Novel Variant

Download Full-text

Genome-Wide Association Study of Rice Rooting Ability at the Seedling Stage

10.21203/rs.3.rs-33742/v1 ◽

2020 ◽

Author(s):

Xin Xu ◽

Junhua Ye ◽

Yingying Yang ◽

Mengchen Zhang ◽

Qun Xu ◽

...

Keyword(s):

Association Study ◽

Root Length ◽

Genetic Basis ◽

Genome Wide Association Study ◽

Genome Wide Association ◽

Root Number ◽

Expression Levels ◽

Rooting Ability ◽

Genome Wide ◽

Population Structure Analysis

Abstract Background Rice rooting ability is a complex agronomical trait that displays heterosis and plays an important role in rice growth and production. Only a few quantitative trait loci (QTLs) have been identified by bi-parental population. More genes or QTLs are required to dissect the genetic architecture of rice rooting ability.Results To characterize the genetic basis for rice rooting ability, we used a natural rice population, genotyped by a 90K single nucleotide polymorphism (SNP) array, to identify the loci associated with rooting-related traits through the genome-wide association study (GWAS). Population structure analysis divided the natural population into two subgroups: indica and japonica. We measured four traits for evaluating rice rooting ability, namely root growth ability (RGA), maximum root length (MRL), root length (RL), and root number (RN). Combined with the association study in three panels consisting of one for the full population, one for indica, and one for japonica, 32 SNPs associated with rooting ability-related traits were identified. Through comparison of the relative expression levels and DNA sequences between germplasms with extreme phenotypes, results showed that LOC_Os05g11810 had non-synonymous variations at the coding region, which may cause differences in root number, and that the expression levels of LOC_Os04g09900 and LOC_Os04g10060 are closely associated with root length variation.Conclusions The goal of our research was to improve understanding of the genetic basis of rice rooting ability and provide useful molecular markers and germplasms for rice root breeding.

Download Full-text