Modern probabilistic and statistical approaches to search for nucleotide sequence options associated with integrated diseases

Rytova, A. I.; Khlebus, Eleonora; Shevtsov, Anton; Куценко, В. А.; Shcherbakova, Natalia; Zharikova, Anastasia A.; Ершова, А. И.; Киселева, А. В.; Boytsov, S. А.; Yarovaya, Elena; Мешков, А. Н.

doi:10.1134/s1022795417100088

Cited by 3 publications

(1 citation statement)

References 78 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To assess the contribution of the SNPs with the low MAF, the variants aggregation tests were developed. Instead of testing each SNP individually, these tests evaluate the cumulative effects of variants [17]. In our work, to find an association between the genetic variants and the oxLDL levels, we used the weighted-sum test (WST) [18], approaches based on the sequence kernel association test (SKAT) [19–22] and the adaptive combination of P -values method (ADA) [23, 24].…”

Section: Introductionmentioning

confidence: 99%

Multiple rare and common variants in APOB gene locus associated with oxidatively modified low-density lipoprotein levels

et al. 2019

View full text Add to dashboard Cite

Oxidatively modified low-density lipoproteins (oxLDL) play an important role in the occurrence and progression of atherosclerosis. To identify the genetic factors influencing the oxLDL levels, we have genotyped 776 DNA samples of Russian individuals for 196,725 single-nucleotide polymorphisms (SNPs) using the Cardio-MetaboChip (Illumina, USA) and conducted genome-wide association study (GWAS). Fourteen common variants in the locus including APOB gene were significantly associated with the oxLDL levels ( P < 2.18 × 10 −7 ). These variants explained only 6% of the variation in the oxLDL levels. Then, we assessed the contribution of rare coding variants of APOB gene to the oxLDL levels. Individuals with the extreme oxLDL levels (48 with the lowest and 48 with the highest values) were selected for targeted sequencing of the region including APOB gene. To evaluate the contribution of the SNPs to the oxLDL levels we used various statistical methods for the association analysis of rare variants: WST, SKAT, and SKAT-O. We revealed that both synonymous and nonsynonymous SNPs affected the oxLDL levels. For the joint analysis of the rare and common variants, we conducted the SKAT-C testing and found a group of 15 SNPs significantly associated with the oxLDL levels ( P = 2.14 × 10 −9 ). Our results indicate that the oxLDL levels depend on both common and rare variants of the APOB gene.

show abstract

Section: Introductionmentioning

confidence: 99%

Multiple rare and common variants in APOB gene locus associated with oxidatively modified low-density lipoprotein levels

et al. 2019

View full text Add to dashboard Cite

show abstract

Safety and Effectiveness of Electrical and Pharmacological Cardioversion in Persistent Atrial Fibrillation. Part 2: Assessment of Safety

Mironov

Vlodzyanovskiy

Yuricheva

et al. 2019

Racionalʹnaâ farmakoterapiâ v kardiologii

View full text Add to dashboard Cite

Aim. To compare safety of new class III antiarrhythmic drug Refralon with direct current cardioversion (DCC) in patients with persistent atrial fibrillation (AF). Material and methods. 60 patients with persistent AF were randomized to groups of DCC (n=30) and pharmacologic conversion (PCV; n=30). There were no significant differences in age, sex, AF duration, concomitant cardiovascular diseases, CHA2DS2-VASc score and echocardiographic parameters between the groups compared. Initial assessment excluded contraindications to restore sinus rhythm (SR). In DCC group two attempts using biphasic synchronized shocks of 150 J and 170 J were performed. In PCV group patients received up to three subsequent intravenous injections of Refralon 10 μg/kg (maximal dose 30 μg/kg). Results. There were no mortality, stroke, transient ischemic attack, ventricular arrhythmia, asystole longer than 3,0 sec (primary safety criteria) in both groups. Prolongation of QT interval longer than 500 ms observed in 1 of 30 patients (3,3%) in DCC group and in 7 of 30 patients (23,3%) in PCV group. 2 patients (one patient in each group; 3,3%) developed asymptomatic bradycardia after conversion to SR that resolved spontaneously within 30 minutes. 95% confidence interval (95%CI) for secondary safety criteria is [0,02-0,38] for QT prolongation and [-0,04-0,04] for bradycardia. Conclusion. Safety of PCV is noninferior to DCC in patients with persistent AF in terms of primary safety criteria and bradyarrhythmias. More frequent QT interval prolongation to values >500 ms observed in PCV group points to necessity of precautions with use of the drug.

show abstract

Eurasian association of cardiology (EAC) guidelines for the prevention and treatment of ventricular heart rhythm disorders and prevention of sudden cardiac death (2022)

Golitsyn

Kostyukevich

Lajovic

et al. 2022

Evrazijskij kardiologičeskij žurnal

View full text Add to dashboard Cite

The EAC Guidelines represent the views of the EAC, and were produced after careful consideration of the scientific and medical knowledge, and the evidence available at the time of their publication. The EAC is not responsible in the event of any contradiction, discrepancy, and/or ambiguity between the EAC Guidelines and any other official recommendations or guidelines issued by the relevant public health authorities, in particular in relation to good use of healthcare or therapeutic strategies. Health professionals are encouraged to take the EAC Guidelines fully into account when exercising their clinical judgment, as well as in the determination and the implementation of preventive, diagnostic, or therapeutic medical strategies; however, the EAC Guidelines do not override, in any way whatsoever, the individual responsibility of health professionals to make appropriate and accurate decisions in consideration of each patient’s health condition and in consultation with that patient and, where appropriate and/or necessary, the patient’s caregiver. Nor do the EAC Guidelines exempt health professionals from taking into full and careful consideration the relevant official updated recommendations or guidelines issued by the competent public health authorities, in order to manage each patient’s case in light of the scientifically accepted data pursuant to their respective ethical and professional obligations. It is also the health professional’s responsibility to verify the applicable rules and regulations relating to drugs and medical devices at the time of prescription.

show abstract

Modern probabilistic and statistical approaches to search for nucleotide sequence options associated with integrated diseases

Cited by 3 publications

References 78 publications

Multiple rare and common variants in APOB gene locus associated with oxidatively modified low-density lipoprotein levels

Multiple rare and common variants in APOB gene locus associated with oxidatively modified low-density lipoprotein levels

Safety and Effectiveness of Electrical and Pharmacological Cardioversion in Persistent Atrial Fibrillation. Part 2: Assessment of Safety

Eurasian association of cardiology (EAC) guidelines for the prevention and treatment of ventricular heart rhythm disorders and prevention of sudden cardiac death (2022)

Contact Info

Product

Resources

About