Table 5.
Association of Alzheimer Disease With Genome-wide Significant Regions in White GWASs
Gene, SNP | Effect Allele | AFCEU | Previously Reported Results in White Cohort
|
Results in African American Cohort
|
||||||
---|---|---|---|---|---|---|---|---|---|---|
Source | AF | P Value | OR (95% CI) | AF | P Value | OR (95% CI) | ||||
CLU | ||||||||||
rs2279590 | T | 0.31 | Lambert et al,19 2009 | NR | 9.2 × 10−8 | 0.87 (0.83–0.92) | 0.12 | .034 | 1.41a (1.03–1.95) | |
rs11136000 | T | 0.35 | Lambert et al,19 2009 | NR | 2.0 × 10−8 | 0.86 (0.82–0.91) | ![]() |
0.56 | .951 | 1.01 (0.84–1.20) |
Seshadri et al,20 2010 | 0.39 | 1.62 × 10−16 | 0.85 (0.82–0.88) | |||||||
Harold et al,21 2009 | 0.40 | 8.5 × 10−10 | 0.86 (0.82–0.90) | |||||||
rs9331888 | G | 0.32 | Lambert et al,19 2009 | NR | 1.4 × 10−7 | 1.15 (1.09–1.22) | 0.20 | >.99 | 1.00 (0.76–1.32) | |
rs9331926b | G | 0.07 | . . . | . . . | . . . | . . . | 0.04 | .020 | 1.96 (1.11–3.48) | |
PICALM | ||||||||||
rs3851179 | T | 0.41 | Seshadri et al,20 2010 | 0.37 | 3.16 × 10−12 | 0.87 (0.84–0.91) | ![]() |
0.16 | .157 | 0.85 (0.68–1.07) |
Harold et al,21 2009 | 0.37 | 1.3 × 10−9 | 0.86 (0.82–0.90) | |||||||
rs17148827c | C | 0.00 | . . . | . . . | . . . | . . . | 0.04 | .0089 | 2.01 (1.19–3.40) | |
rs12795381d | C | 0.14 | . . . | . . . | . . . | . . . | 0.04 | .0086 | 0.49 (0.29–0.84) | |
CR1 | ||||||||||
rs6656401 | A | 0.24 | Lambert et al,19 2009 | NR | 7.9 × 10−9 | 1.20 (1.13–1.28) | 0.07 | .227 | 0.79 (0.54–1.16) | |
rs3818361 | A | 0.26 | Lambert et al,19 2009 | NR | 1.4 × 10−7 | 1.18 (1.11–1.25) | 0.43 | .466 | 0.94 (0.79–1.11) | |
BIN1 | ||||||||||
rs744373 | G | 0.31 | Seshadri et al,20 2010 | 0.29 | 1.59 × 10−11 | 1.15 (1.11–1.20) | 0.48 | .999 | 1.00 (0.84–1.20) | |
rs11685593e | T | 0.21 | . . . | . . . | . . . | . . . | 0.06 | .0098 | 1.66 (1.13–2.45) | |
rs11691237f | T | 0.27 | . . . | . . . | . . . | . . . | 0.10 | .0098 | 1.52 (1.11–2.09) | |
rs7585314g | T | 0.85 | . . . | . . . | . . . | . . . | 0.33 | .0030 | 0.75 (0.62–0.91) | |
CD2AP | ||||||||||
rs9349407 | C | 0.28 | Naj et al,22 2011 | 0.27 | 8.6 × 10−9 | 1.11 (1.07–1.15) | 0.22 | .854 | 0.98 (0.78–1.22) | |
EPHA1 | ||||||||||
rs11767557 | C | 0.20 | Naj et al,22 2011 | 0.19 | 6.0 × 10−10 | 0.90 (0.86–0.93) | 0.18 | .586 | 1.06 (0.86–1.31) | |
rs11762262h | T | 0.20 | . . . | . . . | . . . | . . . | 0.23 | .034 | 1.27 (1.02–1.59) | |
rs4595035i | T | 0.37 | . . . | . . . | . . . | . . . | 0.43 | .0094 | 1.25 (1.06–1.47) | |
MS4A | ||||||||||
rs4938933 | C | 0.50 | Naj et al,22 2011 | 0.39 | 1.7 × 10−9 | 0.88 (0.85–0.92) | 0.30 | .493 | 1.06 (0.88–1.29) | |
rs610932 | T | 0.54 | Hollingworth et al,23 2011 | . . . | 1.8 × 10−14 | 0.90 (0.87–0.92) | 0.49 | .299 | 0.91 (0.77–1.08) | |
rs10792258j | T | 0.20 | . . . | . . . | . . . | . . . | 0.37 | .010 | 0.79 (0.66–0.95) | |
ABCA7 | ||||||||||
rs3752246 | G | 0.19 | Naj et al,22 2011 | 0.19 | 5.8 × 10−7 | 1.15 (1.09–1.21) | 0.04 | .375 | 0.82 (0.53–1.27) | |
rs3764650 | G | 0.11 | Hollingworth et al,23 2011 | . . . | 4.5 × 10−17 | 1.23 (1.18–1.30) | 0.28 | .019 | 1.27 (1.04–1.55) | |
rs3764647k | G | 0.04 | . . . | . . . | . . . | . . . | 0.25 | .0087 | 1.32 (1.07–1.63) | |
CD33 | ||||||||||
rs3865444 | A | 0.32 | Naj et al,22 2011 | 0.30 | 1.6 × 10−9 | 0.91 (0.88–0.93) | 0.09 | .732 | 0.95 (0.70–1.29) | |
rs10419982l | A | 0.45 | . . . | . . . | . . . | . . . | 0.40 | .00054 | 1.38 (1.15–1.65) |
Abbreviations: ABCA7, ATP-binding cassette, subfamily A (ABC1), member 7; AF, effect allele frequency; BIN1, bridging integrator 1; CD2AP, CD2-associated protein; CD33, myeloid-associated antigen CD33; CEU, HapMap’s CEPH (Utah residents with ancestry from Northern and Western Europe) Population; CLU, clusterin; CR1, complement component (3b/4b) receptor 1; ellipses, missing information; EPHA1, ephrin type-A receptor 1; GWAS, genome-wide association study; kb, kilobase; MS4A, the membrane-spanning 4A gene cluster; NPR, not previously reported as associated with Alzheimer disease in whites; NR, not reported; OR, odds ratio; PICALM, phosphatidylinositol binding clathrin assembly protein; SNP, single-nucleotide polymorphism.
Effect estimate directions differ between whites and African Americans.
This SNP was not previously reported as associated with Alzheimer disease in whites (NPR). The lowest P value is in CLU.
This SNP was NPR and is located 15 kb from rs3851179.
This SNP was NPR. This represents the lowest P value observed in PICALM.
This SNP was NPR and flanks rs744375, 6.5 kb away from rs744373.
This SNP was NPR. This represents the most significant P value observed in BIN1.
This SNP was NPR. This represents the lowest P value observed in the BIN1 region.
This SNP was NPR and flanks rs11767557.
This SNP was NPR. This represents the smallest P value observed in the region of EPHA1.
This SNP was NPR. This represents the smallest P value observed in the MS4A region.
This SNP was NPR. This represents the smallest P value observed in ABCA7.
This SNP was NPR and is 63 kb from rs3865444. This represents the lowest P value observed in the CD33 region.