Quantitative assessment of the effect of FGF20 rs1721100 and rs12720208 variant on the risk of sporadic Parkinson's disease: a meta-analysis.

OBJECTIVES: While many studies have investigated the associations between fibroblast growth factor 20 (FGF20) rs1721100 (C/G) and rs12720208 (C/T) polymorphisms and susceptibility to Parkinson's disease (PD), their results are controversial. Our present meta-analysis estimated the overall association between FGF20 rs1721100 and rs12720208 polymorphisms and the risk of sporadic PD. METHODS: We performed a comprehensive literature search of the PubMed, Web of Science, Embase, Chinese National Knowledge Infrastructure, and Wanfang Medicine electronic databases, which was updated in April 2021. Based on strict inclusion and exclusion criteria, the analysis included a total of 10 papers involving 14 studies with 5262 cases of PD and 6075 controls. Review Manager 5.4 software was used to assess the available data from each study. The pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess the association between the FGF20 rs1721100 and rs12720208 polymorphisms and sporadic PD risk. RESULTS: Our results showed that the FGF20 rs1721100 G allele frequency and genotype distribution did not differ between PD patients and controls. Similarly, the FGF20 rs12720208 T allele frequency and genotype distribution did not differ significantly between the two groups. A subgroup analysis of Asian and Caucasian populations also showed the same results. CONCLUSIONS: The results of this meta-analysis indicated that neither the rs1721100 C/G nor the rs12720208 C/T variants were associated with sporadic PD susceptibility.

The Genetic Architecture of a Congenital Heart Defect Is Related to Its Fitness Cost.

In newborns, severe congenital heart defects are rarer than mild ones. This epidemiological relationship between heart defect severity and incidence lacks explanation. Here, an analysis of ~10,000 Nkx2-5+/- mice from two inbred strain crosses illustrates the fundamental role of epistasis. Modifier genes raise or lower the risk of specific defects via pairwise (G×GNkx) and higher-order (G×G×GNkx) interactions with Nkx2-5. Their effect sizes correlate with the severity of a defect. The risk loci for mild, atrial septal defects exert predominantly small G×GNkx effects, while the loci for severe, atrioventricular septal defects exert large G×GNkx and G×G×GNkx effects. The loci for moderately severe ventricular septal defects have intermediate effects. Interestingly, G×G×GNkx effects are three times more likely to suppress risk when the genotypes at the first two loci are from the same rather than different parental inbred strains. This suggests the genetic coadaptation of interacting G×G×GNkx loci, a phenomenon that Dobzhansky first described in Drosophila. Thus, epistasis plays dual roles in the pathogenesis of congenital heart disease and the robustness of cardiac development. The empirical results suggest a relationship between the fitness cost and genetic architecture of a disease phenotype and a means for phenotypic robustness to have evolved.