rs6025

Prospective case-cohort study examining whether 5 prothrombotic SNPs explain the increased venous thromboembolism (VTE) risk after myocardial infarction (MI). Patients with MI had a 1.4-fold increased VTE risk (HR 1.44, 95% CI 1.07-1.96), but adjustment for rs8176719 (ABO), rs6025 (F5), rs1799963 (F2), rs2066865 (FGG), and rs2036914 (F11) did not attenuate this relationship (adjusted HR 1.52). Individual SNPs associated with VTE in non-MI subjects (F5 HR 2.20, ABO HR 1.44), but their combination with MI did not yield excess VTE risk.

This systematic review analyzed genetic associations with gastroschisis from 1980-2017, identifying 14 SNPs from 10 genes associated with crude risk and 30 SNPs from 14 genes with stratified risk. Four SNPs showed significant associations: rs4961 (ADD1, p=0.023), rs5443 (GNB3, p=0.002), rs1042713 (ADRB2, p=0.007), and rs1042714 (ADRB2, p=0.006). The findings suggest genetic susceptibility in gastroschisis is not restricted to gene-environment interactions, with blood pressure regulation genes playing a significant role in vascular disruption pathogenesis.

Mendelian Randomization study examining the causal relationship between obesity (BMI) and venous thromboembolism using 95 BMI-associated SNPs in 7,507 VTE cases and 52,632 European ancestry controls. FTO rs1558902 showed the strongest individual association with VTE (OR 1.07, P = 0.005), and genetically predicted high BMI was significantly associated with increased VTE risk (OR 1.59 per SD increase in BMI, P = 5.8 × 10^-6), providing evidence for a causal relationship between obesity and VTE.

Whole genome sequencing of 44 Ashkenazi Jewish centenarians identified 216 coding variants annotated as pathogenic or likely pathogenic in ClinVar. The study found 130 rare variants (MAF <5%) reported to cause degenerative, neoplastic, and cardiac diseases with various inheritance patterns. Notably, several carriers had no clinical manifestations despite carrying variants linked to serious diseases (e.g., an APOE ε4 homozygote without Alzheimer's disease, a UBQLN2 P525S carrier without ALS). These findings suggest incomplete penetrance and reduced clinical significance for many reported disease mutations.

A large genome-wide association study of venous thromboembolism (VTE) in 9 European ancestry cohorts (4,849 cases total) identified genome-wide significant associations at F5, ABO, F11, and FGG loci. The FGG locus (rs6536024, RR=0.80, p<5.0×10⁻¹³) and F11 locus (rs4253399, RR=1.24, p<5.0×10⁻¹³) showed novel associations with reduced and increased VTE risk respectively. Additional borderline associations (p<5.0×10⁻⁶) were identified near SUSD1 and OTUD7A, representing new candidate genes for VTE.

This case-control association study examined genetic polymorphisms in 237 Russian women to identify variants associated with early reproductive loss and recurrent miscarriage. The study found that DNMT3B rs2424913 (OR=4.44-4.78), DNMT1 rs2228611 (OR=3.0-3.94), and DNMT1 rs8101626 (OR=2.5-3.1) were significantly associated with increased risk of sporadic and recurrent early pregnancy loss, while SYCP3 rs769825641 heterozygotes showed elevated risk of sporadic miscarriage.

A two-stage genome-wide association study identified loci influencing hippocampal volume (HV), total cerebral volume (TCV), and white matter hyperintensities (WMH) in Alzheimer disease-related endophenotypes. Novel genome-wide significant associations (p<5.0×10⁻⁸) were found for HV with SNPs in APOE (p=5.23×10⁻³¹), F5/SELP (p=5.53×10⁻⁹), LHFP, and GCFC2 gene regions in Caucasian discovery cohorts, with replication support in African Americans. Significant associations with different SNPs in the same gene were observed for PICALM (p<1×10⁻⁵ in Caucasians) with HV, SYNPR with TCV, and TTC27 with WMH.

Population-based case-control study of 389 infants with congenital limb deficiencies and 980 controls examining 132 SNPs in 20 candidate genes involved in limb development, angiogenesis, and coagulation. Among non-Hispanic white infants, SNPs in FGF10 (rs10805683: OR=1.99, 95% CI=1.43-2.77; rs13170645: OR=2.37, 95% CI=1.48-3.78) showed significant associations with limb deficiencies after multiple testing correction, with supportive evidence for genes including EN1, WNT7A, CYP26B1, SHH, and TBX5.

Comprehensive review evaluating SNPs as genetic predictors of choroidal neovascularization (CNV) response to photodynamic therapy with verteporfin (PDT-V). The paper examines pharmacogenetic correlations for thrombo-coagulative pathway variants (MTHFR rs1801133, F5 rs6025, F2 rs1799963, F13A1 rs5985), complement/inflammatory variants (CFH, HTRA1, CRP, ARMS2), and VEGFA variants (rs699947, rs2146323), concluding that specific SNPs show clinical plausibility as markers to optimize PDT-V efficacy and guide therapeutic approaches in neovascular macular degeneration.

This review examines 15 years of ischemic stroke susceptibility gene research, organized into three periods: early candidate gene studies (1985-1995) testing variants in hemostasis and homocysteine metabolism genes; expansion period with functional variants discovered from other diseases tested on larger stroke cohorts; and current GWAS-driven large-scale genotyping studies. Key findings include identification of susceptibility loci in CELSR1 (rs6007897, rs4044210 in Japanese populations), PITX2 (rs2200733, rs10033464), and other genes involved in lipid metabolism (APOA5, APOCIII, MLXIPL) and signal transduction (PDE4D, ALOX5AP), with evidence that alleles are often shared across diseases and that careful clinical stratification is critical.

An association study of 201 warfarin-treated patients found that polymorphisms in VKORC1, CYP2C9, CYP2C18, CYP2C19, PROC, and APOE were significantly associated with warfarin dose requirement (P < 0.000175 for VKORC1 and CYP2C9). A multiple regression model incorporating VKORC1, CYP2C9, PROC, and non-genetic factors (age, bodyweight, drug interactions, treatment indication) accounted for 62% of the variance in warfarin dose.

A review article examining the genetic basis of COVID-19 susceptibility and protection from a longevity model perspective. The authors propose that genetic variants in the renin-angiotensin system (ACE, ACE2, AT1R, ANGIOTENSINOGEN), innate immunity genes (TLR4, CCR5, Connexin37), inflammatory cytokines (IL-6, IL-10, TNF-α, IFN-γ), and coagulation factors (PAI-1, Factor V) may influence COVID-19 outcomes, with long-lived individuals (nonagenarians/centenarians) serving as a model for identifying protective genetic profiles.