TABLE 2.
Characteristics of the whole genome linkage and association studies in AD.
| Study Ref. |
Authors | Study Type |
Sample Source | Sample Type |
Age at Onset |
Sample Size | Analytic Approach |
# Markers | Marker Density |
Subset analysis |
|---|---|---|---|---|---|---|---|---|---|---|
| 117 | Pericak-Vance et al. | A | US (NIA, Duke, UCLA, MGH) | multiplex families | ≥60 | 16 families (52 ADs vs. 83 controls) | ARP, ASP, LOD3 | 280 microsatellites | 10–15 cM | E4+ (all ADs with ≥ 1 E4 = 27 families) vs. E4− (≥1 AD member without E4 =27 families)5 |
| 117 | ibid. follow-up | A | 38 families (89 ADs vs. 216 controls) | |||||||
| 118 | Pericak-Vance et al.6 | D | US (NIA, Duke, UCLA, MGH) | multiplex families | >60 | 16 families (52 ADs vs. 83 controls) | ARP, ASP, LOD | 280 microsatellites | 10–15 cM | |
| 118 | ibid. follow-up | D | 38 families (89 ADs vs. 216 controls) | |||||||
| 119 | Zubenko et al. | B | US (Belmont, Pittsburgh) | case-control | >60 | 100 AD cases (autopsied) vs. 100 controls (50 autopsied, 50 90+) | Chi-square | 391 microsatellites | 10 cM | |
| 120 | Kehoe et al. | D | US (NIMH) | sibpairs | ≥65 | 292 sibpairs (230families) | ASP | 237 microsatellites | 16.3 cM | |
| 121 | Pericak-Vance et al.7 | A | US (NIMH, NIA, Duke, UCLA, Vanderbilt) | families | >60 | 466 families (1051 ADs vs. 591 controls; 199 families autopsied) | ARP, ASP | 326 microsatellite | 10 cM | Autopsied (N=199) vs. Not (N=267) |
| 122 | Curtis et al.8 | C | US (NIMH) | families | most ≥65 | 241 families | Conditional non-parametric linkage | 237 microsatellites | 16.3 cM | |
| 123 | Hiltunen et al. | B | Finland | case-control | >60 | 47 ADs vs. 51 controls | Chi-square | 366 microsatellites | 10 cM | |
| 124 | Bacanu et al.9 | C | US (NIMH) | families1 | ≥65 | 65 families (42 with E4+) | ARP (LOAD+psychosis) | 237 microsatellites | 16.3 cM | E4+ (≥2 members with E4+) |
| 125 | Li et al.10,11 | C | US (NIMH, NIA, Duke, UCLA, Vanderbilt) | families | ≥49 | 449 families (1121 ADs vs. 746 controls) | QTL (AAO)3 | 323 microsatellite | 10 cM | |
| 126 | Mayeux et al.12 | A | Caribbean Hispanics | families | mixed (>65 and ≤65) | 79 families (320 subjects) | ARP | 35 markers (Ch12) | 3.4 cM | Late-onset (≥ 65) vs. Early/Mixed onset (<65); E4+ (≥75% of ADs with ≥1 E4) vs. E4− (<75% of ADs with ≥ 1 E4) |
| 127 | Myers et al.2 | A | US (NIMH, NIA)UK | sibpairs | ≥65 | 451 sibpairs (174 new from ref. 120) | ASP | 328 microsatellites (91 additional to ref. 120) | 5 cM (select regions) | E4+ (each sib with ≥ 1 E4= 280 ASP) vs. E4− (all E4−/E4− = 76 ASP) |
| 128 | Olson et al.9 | C | US (NIMH) | sibpairs | ≥60 | 272 sibpairs | ASP with covariates (age, ApoE) | (see 4) | (see 4) | |
| 129 | Blacker et al.8 | A | US (NIMH) | families | ≥50 | 437 families (994 AD vs. 445 controls; 238non-Kehoe families) | ARP, LOD | 381 microsatellites | 9 cM | Late-onset (≥65) vs. Early/Mixed onset (<65) |
| 130 | Farrer et al.13 | B | Inbred Arab community | case-control | ≥60 | 5 ADs vs. 5 controls | Chi-square | 375 microsatellites | 10 cM | |
| 130 | ibid. follow-up | B | 100 ADs vs. 110controls | |||||||
| 131 | Scott et al.14 | C | US (NIMH, NIA, Duke, UCLA, Vanderbilt) | families | ≥49 | 437 multiplex families (1014 ADs vs. 238controls) | Ordered subsets analysis | 336 microsatellites | 10 cM | |
| 132 | Lee et al. | A | Caribbean Hispanics | families | mixed (>65 and ≤65) | 96 families (490subjects; 237 ADs vs.157 controls, others unknown); 104 families (2nd stage, 521 subjects) | ASP, ARP, Affected only dominant model | 340 microsatellites | 10.2 cM | Late-onset (≥65) vs. Early/Mixed onset (<65) |
| 132 | ibid. follow-up | A | 104 families (521subjects) | additional markers on Ch 10, 18, 12 | ||||||
| 133 | Avramopoulos et al.15 | C | US (NIMH) | families | >50 | 148 families (348 ADs vs. 153 controls) | ASP with covariates (delusions, hallucinations) | 381 microsatellites | 9 cM | Late-onset (>65) vs. Early onset (<65) |
| 134 | Holmans et al.16 | C | US (NIMH, NIA) UK | sibpairs | ≥65 | 453 sibpairs (600–789 subjects depending on covariate) | ASP with covariates (mean AAO, difference AAO, mean ROD, difference ROD)3 | 328 microsatellites (91 additional to ref. 120) | 5 cM (select regions) | |
| 135 | Hahs et al. | A | US (Amish) | extended families | ≥58 | 5 families (115 subjects; 40 AD, 9 MCI, 66 controls) | LOD | 407 microsatellites | 7 cM | |
| 136 | Sillen et al. | A | Sweden | multiplex and sibpair families | ≥65 | 71 families (188subjects) | ARP | 365 microsatellites | 9 cM | E4+ = all ADs with ≥ 1 E4 vs. E4− = ≥ 1 AD without any E4 (in E4− families, the E4+ individuals were excluded from analysis) |
Explanation of study types:
A: Linkage analysis of families, relative pairs, independent studies
B: Association analysis of case-controls, independent studies
C: Linkage analysis of families, using alternative analytical methods on largely overlapping datasets with previously published results D: First stage linkage results or results on subsets of other datasets
Explanation of superscripts:
Families with ≥ 2 members with LOAD and psychosis and ≥ 2 members with ApoE e4+
Follow-up study of 120; 80% sample overlap with 121
ARP=affected relative pair; ASP=affected sibpair; LOD=parametric linkage; QTL=quantitative trait loci; AAO=age at onset; ROD=rate of decline
Likely same markers as ref. 120, but not mentioned explicitly in text.
E4 = ApoE e4
Appears to be same study as ref. 117
Sample overlap significantly with ref. 120
Subset of ref. 120
Only results for AD are used herein
Subset of ref. 132
Ch12 results are not follow-up from stage I, but based on previous studies
Subset of 121
Sample overlaps with other NIMH data
Same dataset as ref. 127