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Table 4 Alternative Model Simulation

From: Design considerations in a sib-pair study of linkage for susceptibility loci in cancer

Model A – no heterogeneity:

 

Affected Sibs

Unaffected Sibs

      

Parents

Total

Sampled

Total

Sampled

Zc

Zp

ARE(Zc)

ARE(Zp)

Nc(80%)

Np(80%)

0

2

2

2

0

3.19

 

100

 

304

 

0

2

2

2

1

2.70

2.42

72

38

424

528

0

2

2

2

2

3.03

3.17

90

49

337

308

0

3

2

2

0

6.09

 

364

 

83

 

0

3

2

2

1

6.46

6.00

410

236

74

86

0

3

2

2

2

6.12

6.47

368

206

83

74

2

2

2

2

 

2.88

 

41

 

373

 

2

2

2

2

1

3.17

2.69

49

28

308

427

2

2

2

2

2

3.17

3.33

49

36

308

279

Model B – less common, equally penetrant locus:

0

2

2

2

0

2.37

 

100

 

550

 

0

2

2

2

1

3.04

2.88

165

98

334

373

0

2

2

2

2

2.73

2.81

133

70

415

391

0

3

2

2

0

4.66

 

387

 

142

 

0

3

2

2

1

5.29

5.11

498

310

110

118

0

3

2

2

2

4.86

5.18

421

239

131

115

2

2

2

2

0

2.73

 

66

 

415

 

2

2

2

2

1

2.46

2.22

54

35

511

627

2

2

2

2

2

2.92

2.95

76

52

363

355

Model C – equally common, equally penetrant locus:

0

2

2

2

0

2.38

 

100

 

546

 

0

2

2

2

1

1.93

1.95

66

45

830

813

0

2

2

2

2

2.33

2.36

96

49

569

555

0

3

2

2

0

3.45

 

210

 

260

 

0

3

2

2

1

3.47

3.33

213

131

257

279

0

3

2

2

2

3.48

3.84

214

130

255

210

2

2

2

2

0

2.26

 

45

 

605

 

2

2

2

2

1

2.56

2.44

58

42

472

519

2

2

2

2

2

2.22

2.14

44

27

627

675

  1. Mean Z score, asymptotic relative efficiency per genotype (ARE–see text), and sample size required to attain 80% power for two-point linkage (θ = 0.05) for predisposition to colorectal cancer with a baseline risk of 0.018, a relative risk to carriers of 20, allele frequency of 0.003, with a lifetime penetrance of 0.27, under 3 different heterogeneity models: A) no heterogeneity; B) an equally penetrant, less common (allele frequency 0.001) unlinked predisposing locus; C) an equally penetrant, equally common unlinked predisposing locus. All results based on 500 simulated families and 20 replicate simulations per parameter set.
  2. Zc mean concordant test; Zp mean paired test; ARE(Zc) asymptotic relative efficiency concordant test; ARE(Zp) asymptotic relative efficiency paired test; Nc(80%) number of families required for 80% power using concordant test; Np(80%) number of families required for 80% power using paired test.
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BMC Medical Genetics

ISSN: 1471-2350

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