PMC:4564992 / 21530-23627 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/4564992","sourcedb":"PMC","sourceid":"4564992","source_url":"https://www.ncbi.nlm.nih.gov/pmc/4564992","text":"Adjustment of Genotype Counts for Duos\nInitial investigations indicated that for ambiguous duos (in which the parent and child are both heterozygous), when the number of minor alleles inherited from the father and mother were estimated with SHAPEIT2, the estimates could be biased, depending on the minor allele frequency and which parent (mother or father) was genotyped, leading to inflated test statistics in EMIM. To correct this bias, we devised an adjustment procedure that relies on the fact that we will have tested many SNPs, most of which will not display parent-of-origin effects. (Our adjustment is thus suitable for GWAS data or data from a set of SNPs that are not expected to show parent-of-origin effects; it would not be suitable for analyzing a small number of candidate SNPs.) See Appendix B and Figure S1 for details and an example of the proposed adjustment procedure. Our adjustment procedure involves fitting curves to the estimated counts that correspond to adjusted versions of the curves expected under the null hypothesis. The fitted curves include an adjustment function, f(p), where p is the minor allele frequency. The cell counts for minor alleles inherited from the father (cell 4a) and mother (cell 4b) are then adjusted by respectively subtracting and adding f(p). (This can result in non-integer values for the adjusted counts, which is not a problem given that the multinomial likelihood maximized by EMIM does not specifically require the counts to be integers, see Appendix A.) This procedure ensures that, for the adjusted counts, there should, on average, be far less bias toward transmissions being estimated as coming from one particular parent. A particular SNP that displays clear evidence of transmission from one parent rather than from another, as expected if genuine parent-of-origin effects exist, will, however, be only marginally affected by this adjustment, given that the vast majority of SNPs are assumed to be non-causal. It will be shown later (see Results) that this reduces inflation of the test statistic and slightly increases the power.","divisions":[{"label":"title","span":{"begin":0,"end":38}}],"tracks":[]}