Supplementary Tables:
Supplementary Table 1. The programs and analysis options used in simulations.
Program / Analysis option(s) usedFBAT / Robust variance estimator with dominant, recessive and additive models
TRANSMIT / One affected individual per nuclear family (one)
- with robust estimator (one, ro)
- with bootstrapping (one, bs)
- without robust estimator or bootstrapping* (one)
- with robust estimator (nonuc, ro)
- with bootstrapping (nonuc, bs)
- without robust estimator or bootstrapping* (nonuc)
- with robust estimator (mf, ro)
- with bootstrapping (mf, bs)
- without robust estimator or bootstrapping* (mf)
UNPHASED / NelderMead’s downhill-simplex method for likelihood maximization (-neldermead)
- plain
- with missing (missing)
- with missing and parentrisk (missing,pr)
- plain with controls (cc)
- with missing and controls (missing,cc)
- with missing, parentrisk, and controls (missing,pr,cc)
GENEHUNTER / TDT
PLINK /
- Transmission/Disequilibrium Test (tdt)
- TDT, parent of origin analysis (tdt,poo)
- The parental discordance test (parentdt1)
- The parental discordance test (parentdt2)
- The sib-tdt (sibtdt)
QTDT / ‘Plain’ (no additional options than TDT test for qualitative phenotype)
HHRR** / Genotype and allele based HHRR
- Genotype based, theoretical (GT)
- Genotype based, randomized (GR)
- Allele based, theoretical (AT)
- Allele based, randomized (AR)
MENDEL / Gamete competition
- Model 1 (gc1), where allele frequencies are preset
- Model 2 (gc2), where allele frequencies are estimated
- Analysis model MDom*and the marker locus allele frequencies estimated from the data using MENDEL’s option 6 model 1 (MDom*,fixed1)***
- Analysis model MDom*and the marker locus allele frequencies estimated from the data using MENDEL’s option 6 model 2 (MDom*,fixed2) ***
- Analysis model MRec*and the marker locus allele frequencies estimated from the data using MENDEL’s option 6 model 1 (MRec*,fixed1) ***
- Analysis model MRec*and the marker locus allele frequencies estimated from the data using MENDEL’s option 6 model 2 (MRec*,fixed2) ***
LAMP / Dominant, recessive, additive, multiplicative and free. The ‘maxbits’ was set to 10****.
PSEUDOMARKER / MDom and MRec
* The bootstrapping was done with 100000 samples.
** We have implemented the likelihood based HHRR program used here and it is not published, but is in internal use of Public Health Genomics Unit,National Institute for Health and Welfare.
*** Parametric models used wereMDom*={P(D)=0.01; P(Aff|DD)= P(Aff|D+)=0.01; P(Aff|++)=0}, and MRec*={P(D)=0.01; P(Aff|DD)= 0.01;P(Aff|D+)=P(Aff|++)=0}.NOTE: MENDEL had underflow problems when we used the MRec model, so we had to increase the penetrances and allele frequencies to 0.01. The effect of this slight change in the parametric model is negligible.
**** The maxbits options was used to disregard large pedigrees from the analysis, because without this limitation it would take average of one week to analyze one simulated replicate of schizophrenia (or migraine) pedigrees. The bit complexity of a pedigree, which refers to the depth of the ‘gene-flow-trees’21, is calculated by using formula 2(n-f)-f, where n is the total number of individuals and f is the number of founders.
Supplementary Table 2: Empirical type I error rates on reported 0.01 and 0.05 significance levels and confidence intervals (CI) with continuity correction when using schizophrenia pedigrees based on 1000 replicates when there is no linkage andno association.
Program / α=0.01 / (95% CI) / α=0.05 / (95% CI)FBAT (dom) / 0.0070 / (0.0031-0.0150) / 0.0430 / (0.0316-0.0580)
FBAT (rec) / 0.0070 / (0.0031-0.0150) / 0.0430 / (0.0316-0.0580)
FBAT (add) / 0.0120 / (0.0065-0.0215) / 0.0500 / (0.0377-0.0659)
PSEUDOMARKER (dom; LD|Linkage) / 0.0160 / (0.0095-0.0264) / 0.0630 / (0.0491-0.0803)
PSEUDOMARKER (dom; LD|NoLinkage) / 0.0080 / (0.0037-0.0164) / 0.0440 / (0.0325-0.0591)
PSEUDOMARKER (dom; Linkage|LD) / 0.0100 / (0.0051-0.0190) / 0.0430 / (0.0316-0.0580)
PSEUDOMARKER (dom; Joint) / 0.0140 / (0.0080-0.0240) / 0.0630 / (0.0491-0.0803)
PSEUDOMARKER (rec; LD|Linkage) / 0.0080 / (0.0037-0.0164) / 0.0620 / (0.0482-0.0792)
PSEUDOMARKER (rec; LD|NoLinkage) / 0.0090 / (0.0044-0.0177) / 0.0560 / (0.0429-0.0726)
PSEUDOMARKER (rec; Linkage|LD) / 0.0020 / (0.0003-0.0080) / 0.0260 / (0.0174-0.0384)
PSEUDOMARKER (rec; Joint) / 0.0060 / (0.0024-0.0137) / 0.0580 / (0.0447-0.0748)
GENEHUNTER TDT / 0.0090 / (0.0044-0.0177) / 0.0390 / (0.0282-0.0534)
PLINK (tdt) / 0.0090 / (0.0044-0.0177) / 0.0390 / (0.0282-0.0534)
PLINK (tdt,poo) / 0.0010 / (0.0001-0.0065) / 0.0260 / (0.0174-0.0384)
PLINK (parentdt1) / 0.0090 / (0.0044-0.0177) / 0.0390 / (0.0282-0.0534)
PLINK (parentdt2) / 0.0090 / (0.0044-0.0177) / 0.0390 / (0.0282-0.0534)
PLINK (sib-TDT) / 0.0140 / (0.0080-0.0240) / 0.0510 / (0.0386-0.0670)
HHRR (AT) / 0.0110 / (0.0058-0.0202) / 0.0400 / (0.0291-0.0546)
HHRR (AR) / 0.0100 / (0.0051-0.0190) / 0.0390 / (0.0282-0.0534)
HHRR (GT) / 0.0100 / (0.0051-0.0190) / 0.0590 / (0.0456-0.0759)
HHRR (GR) / 0.0080 / (0.0037-0.0164) / 0.0540 / (0.0412-0.0704)
MENDEL (gc1) / 0.0120 / (0.0065-0.0215) / 0.0500 / (0.0377-0.0659)
MENDEL (gc2) / 0.0130 / (0.0072-0.0227) / 0.0560 / (0.0429-0.0726)
MENDEL (MDom*,fixed1) / 0.0000 / (0.0001-0.0048) / 0.0050 / (0.0018-0.0123)
MENDEL (MDom*,fixed2) / 0.0000 / (0.0001-0.0048) / 0.0010 / (0.0001-0.0065)
MENDEL (MRec*,fixed1) / 0.0010 / (0.0001-0.0065) / 0.0020 / (0.0003-0.0080)
MENDEL (MRec*,fixed2) / 0.0000 / (0.0001-0.0048) / 0.0000 / (0.0001-0.0048)
QTDT / 0.0160 / (0.0095-0.0264) / 0.0550 / (0.0421-0.0715)
TRANSMIT (nonuc) / 0.0060 / (0.0024-0.0137) / 0.0550 / (0.0421-0.0715)
TRANSMIT (nonuc,ro) / 0.0090 / (0.0044-0.0177) / 0.0500 / (0.0377-0.0659)
TRANSMIT (nonuc,bs) / 0.0110 / (0.0058-0.0202) / 0.0510 / (0.0386-0.0670)
TRANSMIT (one) / 0.0050 / (0.0018-0.0123) / 0.0460 / (0.0342-0.0614)
TRANSMIT (one,ro) / 0.0050 / (0.0018-0.0123) / 0.0520 / (0.0394-0.0681)
TRANSMIT (one,bs) / 0.0020 / (0.0003-0.0080) / 0.0550 / (0.0421-0.0715)
TRANSMIT (mf) / 0.0080 / (0.0037-0.0164) / 0.0590 / (0.0456-0.0759)
TRANSMIT (mf,ro) / 0.0120 / (0.0065-0.0215) / 0.0500 / (0.0377-0.0659)
TRANSMIT (mf,bs) / 0.0120 / (0.0065-0.0215) / 0.0490 / (0.0368-0.0648)
LAMP (add) / 0.0040 / (0.0013-0.0110) / 0.0660 / (0.0518-0.0837)
LAMP (rec) / 0.0090 / (0.0044-0.0177) / 0.0780 / (0.0625-0.0968)
LAMP (dom) / 0.0180 / (0.0110-0.0289) / 0.0910 / (0.0743-0.1110)
LAMP (mult) / 0.0050 / (0.0018-0.0123) / 0.0570 / (0.0438-0.0737)
LAMP (free) / 0.0360 / (0.0257-0.0500) / 0.1740 / (0.1513-0.1993)
UNPHASED (plain) / 0.0080 / (0.0037-0.0164) / 0.0400 / (0.0291-0.0546)
UNPHASED (missing) / 0.0090 / (0.0044-0.0177) / 0.0500 / (0.0377-0.0659)
UNPHASED (missing,pr) / 0.0090 / (0.0044-0.0177) / 0.0520 / (0.0394-0.0681)
UNPHASED (plain,cc) / 0.0110 / (0.0058-0.0202) / 0.0390 / (0.0282-0.0534)
UNPHASED (missing,cc) / 0.0070 / (0.0031-0.0150) / 0.0470 / (0.0351-0.0625)
UNPHASED (missing,pr,cc) / 0.0070 / (0.0031-0.0150) / 0.0520 / (0.0394-0.0681)
Supplementary Table 3: Empirical type I error rates on reported 0.01 and 0.05 significance levels and confidence intervals (CI) with continuity correction when using migraine pedigrees based on 1000 replicates when there is no linkage and no association.
Program / α=0.01 / (95% CI) / α=0.05 / (95% CI)FBAT (dom) / 0.0050 / (0.0018-0.0123) / 0.0260 / (0.0174-0.0384)
FBAT (rec) / 0.0050 / (0.0018-0.0123) / 0.0260 / (0.0174-0.0384)
FBAT (add) / 0.0080 / (0.0037-0.0164) / 0.0530 / (0.0403-0.0692)
PSEUDOMARKER (dom; LD|Linkage) / 0.0100 / (0.0051-0.0190) / 0.0500 / (0.0377-0.0659)
PSEUDOMARKER (dom; LD|NoLinkage) / 0.0090 / (0.0044-0.0177) / 0.0500 / (0.0377-0.0659)
PSEUDOMARKER (dom; Linkage|LD) / 0.0070 / (0.0031-0.0150) / 0.0230 / (0.0150-0.0349)
PSEUDOMARKER (dom; Joint) / 0.0120 / (0.0065-0.0215) / 0.0460 / (0.0342-0.0614)
PSEUDOMARKER (rec; LD|Linkage) / 0.0070 / (0.0031-0.0150) / 0.0510 / (0.0386-0.0670)
PSEUDOMARKER (rec; LD|NoLinkage) / 0.0070 / (0.0031-0.0150) / 0.0480 / (0.0360-0.0636)
PSEUDOMARKER (rec; Linkage|LD) / 0.0040 / (0.0013-0.0110) / 0.0250 / (0.0166-0.0372)
PSEUDOMARKER (rec; Joint) / 0.0050 / (0.0018-0.0123) / 0.0420 / (0.0308-0.0569)
GENEHUNTER TDT / 0.0140 / (0.0080-0.0240) / 0.0550 / (0.0421-0.0715)
PLINK (tdt) / 0.0140 / (0.0080-0.0240) / 0.0550 / (0.0421-0.0715)
PLINK (tdt,poo) / 0.0030 / (0.0008-0.0095) / 0.0320 / (0.0223-0.0454)
PLINK (parentdt1) / 0.0140 / (0.0080-0.0240) / 0.0550 / (0.0421-0.0715)
PLINK (parentdt2) / 0.0140 / (0.0080-0.0240) / 0.0550 / (0.0421-0.0715)
PLINK (sib-TDT) / 0.0110 / (0.0058-0.0202) / 0.0540 / (0.0412-0.0704)
HHRR (AT) / 0.0110 / (0.0058-0.0202) / 0.0580 / (0.0447-0.0748)
HHRR (AR) / 0.0100 / (0.0051-0.0190) / 0.0570 / (0.0438-0.0737)
HHRR (GT) / 0.0080 / (0.0037-0.0164) / 0.0610 / (0.0473-0.0781)
HHRR (GR) / 0.0070 / (0.0031-0.0150) / 0.0490 / (0.0368-0.0648)
MENDEL (gc1) / 0.0110 / (0.0058-0.0202) / 0.0570 / (0.0438-0.0737)
MENDEL (gc2) / 0.0160 / (0.0095-0.0264) / 0.0580 / (0.0447-0.0748)
MENDEL (MDom*,fixed1) / 0.0050 / (0.0018-0.0123) / 0.0250 / (0.0166-0.0372)
MENDEL (MDom*,fixed2) / 0.0050 / (0.0018-0.0123) / 0.0360 / (0.0257-0.0500)
MENDEL (MRec*,fixed1) / 0.0030 / (0.0008-0.0095) / 0.0200 / (0.0126-0.0313)
MENDEL (MRec*,fixed2) / 0.0030 / (0.0008-0.0095) / 0.0310 / (0.0215-0.0442)
QTDT / 0.0040 / (0.0013-0.0110) / 0.0380 / (0.0274-0.0523)
TRANSMIT (nonuc) / 0.0140 / (0.0080-0.0240) / 0.0580 / (0.0447-0.0748)
TRANSMIT (nonuc,ro) / 0.0110 / (0.0058-0.0202) / 0.0560 / (0.0429-0.0726)
TRANSMIT (nonuc,bs) / 0.0310 / (0.0215-0.0442) / 0.0810 / (0.0652-0.1001)
TRANSMIT (one) / 0.0130 / (0.0072-0.0227) / 0.0470 / (0.0351-0.0625)
TRANSMIT (one,ro) / 0.0160 / (0.0095-0.0264) / 0.0520 / (0.0394-0.0681)
TRANSMIT (one,bs) / 0.0110 / (0.0058-0.0202) / 0.0480 / (0.0360-0.0636)
TRANSMIT (mf) / 0.0090 / (0.0044-0.0177) / 0.0470 / (0.0351-0.0625)
TRANSMIT (mf,ro) / 0.0080 / (0.0037-0.0164) / 0.0490 / (0.0368-0.0648)
TRANSMIT (mf,bs) / 0.0090 / (0.0044-0.0177) / 0.0520 / (0.0394-0.0681)
LAMP (add) / 0.0100 / (0.0051-0.0190) / 0.0750 / (0.0598-0.0935)
LAMP (rec) / 0.0110 / (0.0058-0.0202) / 0.0890 / (0.0724-0.1088)
LAMP (dom) / 0.0180 / (0.0110-0.0289) / 0.0810 / (0.0652-0.1001)
LAMP (mult) / 0.0120 / (0.0065-0.0215) / 0.0740 / (0.0589-0.0925)
LAMP (free) / 0.0430 / (0.0316-0.0580) / 0.1900 / (0.1664-0.2160)
UNPHASED (plain) / 0.0210 / (0.0134-0.0325) / 0.0730 / (0.0580-0.0914)
UNPHASED (missing) / 0.0100 / (0.0051-0.0190) / 0.0520 / (0.0394-0.0681)
UNPHASED (missing,pr) / 0.0120 / (0.0065-0.0215) / 0.0510 / (0.0386-0.0670)
UNPHASED (plain,cc) / 0.0070 / (0.0031-0.0150) / 0.0570 / (0.0438-0.0737)
UNPHASED (missing,cc) / 0.0100 / (0.0051-0.0190) / 0.0490 / (0.0368-0.0648)
UNPHASED (missing,pr,cc) / 0.0100 / (0.0051-0.0190) / 0.0510 / (0.0386-0.0670)
Supplementary Table 4: Empirical type I error rates on reported 0.01 and 0.05 significance levels and confidence intervals (CI) with continuity correction when using schizophrenia pedigrees based on 1000 replicates when true underlying model of inheritance was MRec, andcomplete linkage and no association was assumed.
RecessiveProgram / α=0.01 / (95% CI) / α=0.05 / (95% CI)
FBAT (rec) / 0.0120 / (0.0065-0.0215) / 0.0560 / (0.0429-0.0726)
PSEUDOMARKER (rec;LD|Linkage) / 0.0110 / (0.0058-0.0202) / 0.0430 / (0.0316-0.0580)
GENEHUNTER TDT / 0.0690 / (0.0544-0.0870) / 0.1760 / (0.1532-0.2014)
PLINK (tdt) / 0.0690 / (0.0544-0.0870) / 0.1760 / (0.1532-0.2014)
PLINK (tdt,poo) / 0.0350 / (0.0249-0.0489) / 0.1250 / (0.1055-0.1475)
PLINK (parentdt1) / 0.0690 / (0.0544-0.0870) / 0.1760 / (0.1532-0.2014)
PLINK (parentdt2) / 0.0690 / (0.0544-0.0870) / 0.1760 / (0.1532-0.2014)
PLINK (sib-TDT) / 0.0630 / (0.0491-0.0803) / 0.1660 / (0.1438-0.1909)
HHRR (AT) / 0.0120 / (0.0065-0.0215) / 0.0430 / (0.0316-0.0580)
HHRR (AR) / 0.0110 / (0.0058-0.0202) / 0.0480 / (0.0360-0.0636)
HHRR (GT) / 0.0140 / (0.0080-0.0240) / 0.0640 / (0.0500-0.0815)
HHRR (GR) / 0.0110 / (0.0058-0.0202) / 0.0560 / (0.0429-0.0726)
MENDEL (gc1) / 0.1170 / (0.0981-0.1389) / 0.2380 / (0.2122-0.2659)
MENDEL (gc2) / 0.1310 / (0.1110-0.1539) / 0.2600 / (0.2333-0.2886)
MENDEL (MRec*,fixed1) / 0.0000 / (0.0001-0.0048) / 0.0100 / (0.0051-0.0190)
MENDEL (MRec*,fixed2) / 0.0000 / (0.0001-0.0048) / 0.0010 / (0.0001-0.0065)
QTDT / 0.0050 / (0.0018-0.0123) / 0.0490 / (0.0368-0.0648)
TRANSMIT (nonuc) / 0.1310 / (0.1110-0.1539) / 0.2550 / (0.2285-0.2834)
TRANSMIT (nonuc,ro) / 0.0190 / (0.0118-0.0301) / 0.0820 / (0.0661-0.1012)
TRANSMIT (nonuc,bs) / 0.0170 / (0.0103-0.0277) / 0.0760 / (0.0607-0.0946)
TRANSMIT (one) / 0.0110 / (0.0058-0.0202) / 0.0570 / (0.0438-0.0737)
TRANSMIT (one,ro) / 0.0140 / (0.0080-0.0240) / 0.0620 / (0.0482-0.0792)
TRANSMIT (one,bs) / 0.0110 / (0.0058-0.0202) / 0.0600 / (0.0465-0.0770)
TRANSMIT (mf) / 0.1320 / (0.1120-0.1549) / 0.2550 / (0.2285-0.2834)
TRANSMIT (mf,ro) / 0.0170 / (0.0103-0.0277) / 0.0860 / (0.0697-0.1055)
TRANSMIT (mf,bs) / 0.0160 / (0.0095-0.0264) / 0.0830 / (0.0670-0.1023)
LAMP (rec) / 0.0710 / (0.0562-0.0892) / 0.1840 / (0.1607-0.2097)
UNPHASED (plain) / 0.0090 / (0.0044-0.0177) / 0.0590 / (0.0456-0.0759)
UNPHASED (missing) / 0.1370 / (0.1166-0.1602) / 0.3050 / (0.2768-0.3347)
UNPHASED (missing,pr) / 0.0500 / (0.0377-0.0659) / 0.1730 / (0.1503-0.1982)
UNPHASED (plain,cc) / 0.0090 / (0.0044-0.0177) / 0.0560 / (0.0429-0.0726)
UNPHASED (missing,cc) / 0.1240 / (0.1045-0.1464) / 0.2910 / (0.2632-0.3204)
UNPHASED (missing,pr,cc) / 0.2720 / (0.2448-0.3009) / 0.4980 / (0.4666-0.5294)
Supplementary Table 5: Empirical type I error rates on reported 0.01 and 0.05 significance levels and confidence intervals (CI) with continuity correction when using migraine pedigrees based on 1000 replicates when true underlying model of inheritance was MDom, and complete linkage and no association was assumed.
DominantProgram / α=0.01 / (95% CI) / α=0.05 / (95% CI)
FBAT (dom) / 0.0030 / (0.0008-0.0095) / 0.0290 / (0.0199-0.0419)
PSEUDOMARKER (dom; LD|Linkage) / 0.0090 / (0.0044-0.0177) / 0.0470 / (0.0351-0.0625)
GENEHUNTER TDT / 0.0540 / (0.0412-0.0704) / 0.1230 / (0.1036-0.1453)
PLINK (tdt) / 0.0540 / (0.0412-0.0704) / 0.1230 / (0.1036-0.1453)
PLINK (tdt,poo) / 0.0090 / (0.0044-0.0177) / 0.0770 / (0.0616-0.0957)
PLINK (parentdt1) / 0.0540 / (0.0412-0.0704) / 0.1230 / (0.1036-0.1453)
PLINK (parentdt2) / 0.0540 / (0.0412-0.0704) / 0.1230 / (0.1036-0.1453)
PLINK (sib-TDT) / 0.0460 / (0.0342-0.0614) / 0.1360 / (0.1157-0.1592)
HHRR (AT) / 0.0110 / (0.0058-0.0202) / 0.0550 / (0.0421-0.0715)
HHRR (AR) / 0.0120 / (0.0065-0.0215) / 0.0520 / (0.0394-0.0681)
HHRR (GT) / 0.0110 / (0.0058-0.0202) / 0.0630 / (0.0491-0.0803)
HHRR (GR) / 0.0100 / (0.0051-0.0190) / 0.0540 / (0.0412-0.0704)
MENDEL (gc1) / 0.0990 / (0.0815-0.1196) / 0.1910 / (0.1674-0.2171)
MENDEL (gc2) / 0.1100 / (0.0916-0.1314) / 0.2010 / (0.1769-0.2275)
MENDEL (MDom*,fixed1) / 0.0050 / (0.0018-0.0123) / 0.0280 / (0.0190-0.0408)
MENDEL (MDom*,fixed2) / 0.0030 / (0.0008-0.0095) / 0.0210 / (0.0134-0.0325)
QTDT / 0.0050 / (0.0018-0.0123) / 0.0370 / (0.0265-0.0512)
TRANSMIT (nonuc) / 0.0860 / (0.0697-0.1055) / 0.1930 / (0.1693-0.2191)
TRANSMIT (nonuc,ro) / 0.0170 / (0.0103-0.0277) / 0.0670 / (0.0527-0.0848)
TRANSMIT (nonuc,bs) / 0.0340 / (0.0240-0.0477) / 0.0860 / (0.0697-0.1055)
TRANSMIT (one) / 0.0220 / (0.0142-0.0337) / 0.0920 / (0.0752-0.1121)
TRANSMIT (one,ro) / 0.0260 / (0.0174-0.0384) / 0.0980 / (0.0806-0.1185)
TRANSMIT (one,bs) / 0.0250 / (0.0166-0.0372) / 0.0920 / (0.0752-0.1121)
TRANSMIT (mf) / 0.0920 / (0.0752-0.1121) / 0.1890 / (0.1655-0.2150)
TRANSMIT (mf,ro) / 0.0270 / (0.0182-0.0396) / 0.0910 / (0.0743-0.1110)
TRANSMIT (mf,bs) / 0.0300 / (0.0207-0.0431) / 0.0920 / (0.0752-0.1121)
LAMP (dom) / 0.0210 / (0.0134-0.0325) / 0.1120 / (0.0935-0.1336)
UNPHASED (plain) / 0.0250 / (0.0166-0.0372) / 0.0800 / (0.0643-0.0990)
UNPHASED (missing) / 0.0380 / (0.0274-0.0523) / 0.1000 / (0.0825-0.1207)
UNPHASED (missing,pr) / 0.0330 / (0.0232-0.0466) / 0.1020 / (0.0843-0.1228)
UNPHASED (plain,cc) / 0.0140 / (0.0080-0.0240) / 0.0660 / (0.0518-0.0837)
UNPHASED (missing,cc) / 0.0200 / (0.0126-0.0313) / 0.0740 / (0.0589-0.0925)
UNPHASED (missing,pr,cc) / 0.0200 / (0.0126-0.0313) / 0.0720 / (0.0571-0.0903)
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Supplementary Table 6. The effect of missing parental genotypes and sib-ship size on type I error rate (α=0.05 significance level). The number of pedigrees in analysis were; 200 triads (one affected child) and 100 sib-ships (two, three or four affected children). Additional 200 controls were included into all analysis. The true (i.e., generating) model of inheritance was MRec, and complete linkage between disease and SNP marker (minor allele frequency 0.1) was assumed. A cell with gray background and bold facefont indicates that empirical error rate is at least double than what is expected (empirical p-value ≥ 0.1).
Program / Parental genotypes known / One parental genotype unknown / Parental genotypes unknownNumber of (affected) kids / Number of (affected) kids / Number of (affected) kids
1 / 2 / 3 / 4 / 1 / 2 / 3 / 4 / 1 / 2 / 3 / 4
FBAT (dom) / 0.08 / 0.05 / 0.06 / 0.08 / 0.00* / 0.00* / 0.00* / 0.00* / 0.00* / 0.00* / 0.00* / 0.00*
FBAT (rec) / 0.08 / 0.05 / 0.06 / 0.08 / 0.00* / 0.00* / 0.00* / 0.00* / 0.00* / 0.00* / 0.00* / 0.00*
FBAT (add) / 0.05 / 0.04 / 0.04 / 0.06 / 0.00* / 0.00* / 0.00* / 0.00* / 0.00* / 0.00* / 0.00* / 0.00*
PSEUDOMARKER (rec; LD|Linkage) / 0.10 / 0.04 / 0.05 / 0.04 / 0.09 / 0.04 / 0.06 / 0.05 / 0.05 / 0.04 / 0.06 / 0.05
GH TDT / 0.05 / 0.17 / 0.25 / 0.33 / 0.00* / 0.00* / 0.00* / 0.00* / 0.00* / 0.00* / 0.00* / 0.00*
HHRR (GT) / 0.05 / 0.04 / 0.06 / 0.06 / 0.05 / 0.05 / 0.06 / 0.05 / 0.06 / 0.06 / 0.06 / 0.06
HHRR (GR) / 0.06 / 0.04 / 0.06 / 0.06 / 0.06 / 0.05 / 0.05 / 0.04 / 0.06 / 0.05 / 0.05 / 0.05
HHRR (AT) / 0.05 / 0.04 / 0.05 / 0.05 / 0.05 / 0.04 / 0.05 / 0.05 / 0.05 / 0.05 / 0.06 / 0.06
HHRR (AR) / 0.05 / 0.04 / 0.05 / 0.04 / 0.04 / 0.04 / 0.05 / 0.05 / 0.05 / 0.04 / 0.06 / 0.05
MENDEL (gc1) / 0.06 / 0.17 / 0.25 / 0.33 / 0.03 / 0.30 / 0.62 / 0.68 / 0.01 / 1.00 / 1.00 / 1.00
MENDEL (MRec*,fixed1) / 0.02 / 0.02 / 0.03 / 0.02 / 0.01 / 0.01 / 0.02 / 0.01 / 0.01 / 0.03 / 0.03 / 0.02
QTDT / 0.04 / 0.04 / 0.03 / 0.05 / 0.00* / 0.00* / 0.00* / 0.00* / 0.00* / 0.00* / 0.00* / 0.00*
TRANSMIT (nonuc) / 0.05 / 0.17 / 0.25 / 0.33 / 0.05 / 0.39 / 0.67 / 0.56 / 0.00* / 0.06 / 0.01 / 0.00*
TRANSMIT (nonuc,ro) / 0.05 / 0.05 / 0.04 / 0.07 / 0.05 / 0.17 / 0.23 / 0.21 / 0.00* / 1.00 / 1.00 / 1.00
TRANSMIT (nonuc,bs) / 0.04 / 0.04 / 0.03 / 0.05 / 0.04 / 0.12 / 0.16 / 0.06 / 0.01 / 0.00* / 0.00* / 0.00*
TRANSMIT (one) / 0.05 / 0.04 / 0.04 / 0.06 / 0.05 / 0.12 / 0.18 / 0.14 / 0.00* / 1.00 / 1.00 / 1.00
TRANSMIT (one,ro) / 0.05 / 0.05 / 0.04 / 0.07 / 0.05 / 0.17 / 0.23 / 0.21 / 0.00* / 1.00 / 1.00 / 1.00
TRANSMIT (one,bs) / 0.04 / 0.04 / 0.03 / 0.05 / 0.04 / 0.12 / 0.17 / 0.13 / 0.01 / 0.97 / 1.00 / 1.00
LAMP (rec) / 0.05 / 0.05 / 0.04 / 0.05 / 0.05 / 0.04 / 0.06 / 0.04 / 0.06 / 0.04 / 0.06 / 0.05
UNPHASED (plain,cc) / 0.06 / 0.05 / 0.04 / 0.07 / 0.00* / 0.00* / 0.00* / 0.00* / 0.00* / 0.00* / 0.00* / 0.00*
UNPHASED (missing,cc) / 0.06 / 0.05 / 0.04 / 0.07 / 0.05 / 0.12 / 0.18 / 0.15 / 0.05 / 0.82 / 1.00 / 1.00
UNPHASED (missing,pr,cc) / 0.06 / 0.07 / 0.07 / 0.10 / 0.05 / 0.26 / 0.41 / 0.42 / 0.00* / 0.99 / 1.00 / 1.00
PLINK (tdt) / 0.05 / 0.17 / 0.25 / 0.33 / 0.00* / 0.00* / 0.00* / 0.00* / 0.00* / 0.00* / 0.00* / 0.00*
PLINK (tdt,poo) / 0.03 / 0.13 / 0.19 / 0.28 / 0.00* / 0.00* / 0.00* / 0.00* / 0.00* / 0.00* / 0.00* / 0.00*
PLINK (parentdt1) / 0.05 / 0.17 / 0.25 / 0.33 / 0.00* / 0.00* / 0.00* / 0.00* / 0.00* / 0.00* / 0.00* / 0.00*
PLINK (parentdt2) / 0.05 / 0.17 / 0.25 / 0.33 / 0.00* / 0.00* / 0.00* / 0.00* / 0.00* / 0.00* / 0.00* / 0.00*
PLINK (sib-TDT) / 0.05 / 0.17 / 0.25 / 0.33 / 0.00* / 0.00* / 0.00* / 0.00* / 0.00* / 0.00* / 0.00* / 0.00*
*) There is no informative data for this selected analysis option
Supplementary Figures:
Supplementary Figure 1. Binomial probability of a lod score greater than 3 (exact p-value) as a function of the number of informative meioses.
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