PMC:4564992 / 41524-43932 JSONTXT

{"project":"2_test","denotations":[{"id":"26320892-23297363-2052550","span":{"begin":63,"end":65},"obj":"23297363"},{"id":"26320892-23297363-2052551","span":{"begin":2406,"end":2408},"obj":"23297363"}],"text":"TOF Data\nWe also re-analyzed the data of Cordell et al. (2013),35 testing for a paternally inherited imprinting effect on chromosome 12 and a maternally inherited imprinting effect on chromosome 13. Without using estimated parent of origin, the analysis on chromosome 12 gave a minimum p value of 2.10 × 10−8 at rs11065987; using estimated parent of origin gave a p value of 4.16 × 10−7 at the same SNP. On chromosome 13, the most significant SNP, rs7982677, gave p values of 9.54 × 10−7 and 6.97 × 10−6 when not estimating and estimating parent of origin, respectively. Plots of these analyses, with and without using estimated parent of origin, are shown in Figures S5 and S6. Again we see a general decrease in the significance of the most significant results when using haplotype estimation, weakening the evidence that these genomic regions genuinely harbor imprinting effects.\nTable 2 shows counts of the number of trios or duos falling into the ambiguous categories and their resolution when using haplotype estimation with SHAPEIT2 for the TOF data. For SNP rs11065987 on chromosome 12, it can be seen that, for case-parent trios and case-father duos, the number of risk alleles inherited from the father and mother are approximately equal; however, for case-mother duos, many more risk alleles are estimated to be inherited from the mother: 10.007, as compared to 1.993 from the father. This results in the initial estimated paternally inherited imprinting effects odds ratio Ip = 1.662 reducing to 1.555, thus decreasing the significance (and increasing the p value). Similarly, for SNP rs7982677 on chromosome 13, it can be seen that more alleles are inherited from the father than from the mother for all trios and duos, resulting in an initial estimated maternally inherited imprinting effect odds ratio Im = 1.577 reducing to 1.504. Again, although the significance is decreased when using haplotype estimation, it corresponds to the use of more information (an additional 43 families on chromosome 12 and an additional 29 families on chromosome 14) and thus should be considered the more reliable result. We note that the decrease of significance seen in this dataset with respect to testing imprinting effects (Ip or Im) has no impact on the significance of associations due to the case subject’s own genotype, findings which have in any case already been replicated in independent cohorts.35"}