Fig. 5: Single common variant significantly associated with planum temporale asymmetry in genome-wide scanning.

We performed a genome-wide association study (GWAS) based on 29,470 UK Biobank subjects to find associations between common single nucleotide polymorphisms (SNP) and planum temporale asymmetry. a GWAS of planum temporale asymmetry spotlights single SNP. The Manhattan plot depicts the single significantly associated SNP rs41298373 at locus 10p14. b Quantile-Quantile plot for the performed GWAS. The P-value associated with rs41298373 clearly exceeds the expected P-values from the corresponding reference distribution. c Regional plot to zoom in on the identified genomic locus rs41298373. The identified SNP locus lies within exon 9 of the gene ITIH5 (ENSG00000123243). d GWAS associations with rs41298373 based on the GWAS Catalog. This SNP was further associated with several measurements of brain morphology or cortical surface and thickness. In total, previous GWAS associated rs41298373 with 13 phenotypes, including the here observed planum temporale asymmetry (i.e., second bar). e GWAS associations with ITIH5 based on the GWAS Catalog. The identified gene ITIH5 was further associated with a total of 24 phenotypes spanning measurements of blood proteins, brain morphology, gut microbiome, or ovarian reserve. f Summary of GWAS based on left, respectively right, planum temporale volume. GWAS of left planum temporale identified significantly associated SNPs influencing the expression of 10 genes, including the ITIH5 gene. GWAS of right planum temporale volume identified SNPs associated with the expression of six genes. Notably, ITIH5 was not absent among these genes. g Genetic correlation between genetic basis (GWAS summary statistics) underlying left and right planum temporale volume, planum temporale asymmetry, as well as ASD and SCZ. The left and right planum temporale volumes were significantly, yet imperfectly correlated. The remaining unexplained residual variance suggests a partly diverging genetic architecture. The genetic architecture underlying planum temporale asymmetry was significantly correlated only with the volume in the left hemisphere but not that of the right one. We did not find a significant correlation with any of the disorders. Plots were generated using FUMA software¹⁵⁸. We isolated a specific genetic locus that may mediate genetically controlled brain asymmetry. In addition, we quantified the different genetic control of left and right planum temporale volume.