For the sum-score we identified 36 GWS exonic non-synonymous SNPs (ExNS), of which 29 overlapped with the 134 ExNS SNPs identified in item-level analyses (Supplementary Data 48). 10 of these overlapping ExNS SNPs are located in a well-known inversion on chromosome 173. Overall, 105 ExNS SNPs were specifically associated with one or more of the individual items and went unnoticed in sum-score analysis, showing that item-level analyses superadded to the identification of SNPs that are highly likely to have functional consequences. As an example, we highlight two ExNS SNPs, not GWS for the neuroticism sum-score19, that may be viable candidates for functional follow-up. Of all ExNS SNPs associated to neuroticism items, rs45510500, located in exon 42 of KIAA1109, had the highest CADD score (35). rs45510500 is a missense mutation that leads to an amino acid change of Arginine to Tryptophan. The second SNP, rs3130618 in exon 3 of GPANK1 with a CADD score of 34, is a missense mutation resulting in an Arginine to Leucine change. rs3130618 has a regulome database score of 1f, implying that it is likely to affect binding and to affect expression of a gene target.
