Derringer, J. | Search bioRxiv

bioRxiv2018

Explaining heritable variance in human character

Personality is moderately heritable (around 40%), across a variety of measures [1]. Non-linear genetic influences (subsumed by the influence of the \"dominance\" factor in the heritability literature) likely play a large role in the genetics of personality [2], even more so than for other phenotypes. Zwir and colleagues [3] sought to identify sets of SNPs that, through both additive and interactive effects, explain the previously observed heritability of personality. The abstract reported identification of a set of SNPs that \"explained nearly all the heritability expected for character in each sample (50 to 58%).\" This reported effect size is extraordinary. The papers Supplemental Materials reveal how such an estimate occurred.\n\nThe variance explained in character by the identified SNPs are the R2 values from regression models in which polygenic scores were fit and evaluated within each of three samples (Finnish, ...

genetics↗

bioRxiv2018

Imputation of Behavioral Candidate Gene Repeat Polymorphisms in 486,551 Publicly-Available UK Biobank Individuals.

Some of the most widely studied polymorphisms in psychiatric genetics include variable number tandem repeat polymorphisms (VNTRs) in SLC6A3, DRD4, SLC6A4, and MAOA. While initial findings suggested large effects, their importance with respect to psychiatric phenotypes is the subject of much debate with broadly conflicting results. Despite broad interest, these loci remain absent from the largest available samples, such as the UK Biobank, limiting researchers ability to test these contentious hypotheses rigorously in large samples. Here, using two independent reference datasets, we report out-of-sample imputation accuracy estimates of >0.96 for all four VNTR polymorphisms and one modifying SNP, depending on the reference and target dataset. We describe the imputation procedures of these candidate polymorphisms in 486,551 UK Biobank individuals, and have made the imputed polymorphism data available to UK Biobank researchers. This resource, provided to the community, will allow the most rigorous tests to-date of the roles of these polymorphisms in behavioral and psychiatric phenotypes.

genetics↗