rs4702

This study evaluated the use of polygenic scores (PGS) based on 10 top SNPs from European GWAS meta-analysis of antisocial behavior to predict liability to severe criminal behavior (homicide) in a Russian cohort of 227 offenders and 254 controls. A PGS based on rs993137 (CADM2), rs458806 (REV3L), rs11720703 (FOXP1), and rs1476535 (FOXP2) explained 1.5% of variance in liability to antisocial behavior, while the combined genetic model with social factors (traumatic brain injury, chronic disease, tobacco smoking) explained up to 21.2% of variance (p = 2 × 10⁻¹³), demonstrating that social factors have substantially greater predictive impact than genetic variants alone.

This paper presents CalPen, a web-based tool for calculating penetrance (disease likelihood given a mutation) in complex genetic disorders. The authors validated CalPen against published penetrance calculations for schizophrenia-associated copy number variants (CNVs) and single nucleotide polymorphisms (SNPs). They analyzed 15 CNVs in 39,059 schizophrenia patients and 55,084 controls (average penetrance 7%, ranging from ~1.4% for 15q11.2 deletions to ~20% for 22q11.21 CNVs) and 145 SNPs in 45,405 patients and 122,761 controls (average penetrance 0.7%, with rs1801028 showing the highest at 1.6%).

A genome-wide eQTL analysis in >1400 blood samples identified 10 independent loci regulating proprotein convertase (PCSK) gene expression, with rs4702 as a novel cis-eQTL for FURIN showing genome-wide significance (p=6.14e-10). The rs4702 AA genotype was significantly associated with increased diastolic (p=0.012) and systolic (p=0.035) blood pressure, as well as systemic vascular resistance (p=0.003), with effect sizes of ~0.75 mmHg diastolic and ~1.0 mmHg systolic per coded allele.