PMC:4564992 / 23682-25789 JSONTXT

{"project":"2_test","denotations":[{"id":"26320892-16224189-2052535","span":{"begin":101,"end":103},"obj":"16224189"}],"text":"We carried out a simulation study to investigate the performance of our proposed new approach. SimPed33 was used to simulate 1,000 (for investigation of power) or 5,000 (for investigation of type I error) replicates of datasets, each with 1,500 family units (case-parent trios, case-mother duos, or case-father duos) typed at 200 SNPs across a “chromosome.” Haplotype blocks of eight SNPs in length were simulated; this was repeated 25 times to give the total of 200 SNPs. If a causal SNP was required (as when estimating power), then the 100th SNP was used. The power or type I error of PREMIM and EMIM under various models was then calculated; detection at SNP numbers 97 to 104 was used as evidence of a true or false finding. Several different PREMIM and EMIM tests were considered: (1) using the parent of origin of alleles as estimated from SHAPEIT2, with and without genotype-count adjustment, (2) using the previous version of PREMIM and EMIM, which categorizes ambiguous trios or duos into a single cell (cell 9 for trios or cell 4 for duos) without estimating parent of origin, and (3) using the known (simulated) parent of origin of alleles. The p value thresholds used to examine power were 10−12, 10−10, and 10−6. For type I error, the p value thresholds used were 6.25 × 10−3, 1.25 × 10−3, and 1.25 × 10−4, which correspond to family-wise error rates (FWERs) of 0.05, 0.01, and 0.001, under the assumption that the eight SNPs tested are independent. Unless otherwise stated, the default options in SHAPEIT2 were used (“−burn 7 −prune 8 −main 20”). For faster analysis (used in the simulation study for case-parent trios), SHAPEIT2 with fast MCMC options (“−burn 1 −prune 1 −main 1”) was used. Tests were performed with PREMIM and EMIM to detect (1) maternally inherited imprinting effects, (2) maternally inherited imprinting effects while allowing for child effects, and, for case-parent trios and type I errors only, (3) maternally inherited imprinting effects while allowing for maternal effects and (4) maternally inherited imprinting effects while allowing for maternal and child effects."}