Table1.
Results of Genome-wide Family-based Association Analysis of Imputed Genotypes using Three Large Collections of Multiplex AD Study Families.
| Panel A: Functional variants; SNPs that are either in a gene or in LD with the gene. |
| SNP | Chr | Position | Fams (MA) |
Zscore (MA) |
P-value (MA) |
Effect Direction (MA) |
Gene | NIMH | NCRAD | NIA | Approach |
|---|---|---|---|---|---|---|---|---|---|---|---|
| rs7609954 | 3 | 61636156 | 696 | 5.492 | 3.98E-08 | ++++++ | PTPRG | 8.73E-03 | 7.57E-03 | 1.73E-03 | 2 |
| rs1347297 | 2 | 179244986 | 640 | 5.469 | 4.53E-08 | +++ | OSBPL6 | 3.65E-02 | 5.85E-02 | 1.24E-06 | 1 |
| rs11749176 | 5 | 44145931 | 840 | 5.218 | 1.81E-07 | ++++++ | FGF10 | 5.95E-02 | 3.74E-02 | 3.12E-02 | 2 |
| rs12378800 | 9 | 100631820 | 438 | 5.218 | 1.81E-07 | ++++++ | FOXE1 | 6.33E-02 | 1.92E-02 | 1.05E-01 | 2 |
| rs185968827 | 6 | 56708510 | 844 | 5.158 | 2.49E-07 | ++++++ | DST | 1.12E-02 | 4.09E-02 | 5.25E-02 | 2 |
| rs62400067 | 6 | 20592984 | 502 | 5.092 | 3.54E-07 | ++++++ | CDKAL1 | 2.51E-02 | 6.81E-02 | 1.65E-04 | 2 |
| rs9304861 | 19 | 35271888 | 622 | 5.082 | 3.74E-07 | ++++++ | ZNF599 | 2.19E-02 | 5.92E-03 | 3.97E-02 | 2 |
| rs9994441 | 4 | 170094562 | 622 | 4.99 | 6.05E-07 | ++++++ | SH3RF1 | 5.92E-01 | 1.52E-02 | 1.11E-01 | 2 |
| rs3931397 | 4 | 149079497 | 524 | 4.984 | 6.22E-07 | ++++++ | NR3C2 | 1.62E-02 | 1.85E-02 | 2.73E-01 | 2 |
| rs72953347 | 2 | 179274829 | 670 | 4.98 | 6.36E-07 | +++ | OSBPL6 | 3.27E-02 | 2.72E-01 | 3.39E-06 | 2 |
| rs115500410 | 5 | 76852235 | 922 | 4.963 | 6.94E-07 | ++++++ | WDR41 | 1.85E-01 | 1.88E-01 | 3.06E-04 | 2 |
| rs56146971 | 14 | 91920101 | 904 | 4.941 | 7.76E-07 | ++++++ | SMEK1 | 7.24E-03 | 5.18E-02 | 7.94E-03 | 2 |
| rs77220498 | 9 | 100700832 | 440 | 4.946 | 7.59E-07 | ++++++ | HEMGN | 2.16E-01 | 1.31E-02 | 1.15E-01 | 2 |
| rs6491411 | 13 | 98904568 | 872 | 4.911 | 9.08E-07 | ++++++ | FARP1 | 1.91E-01 | 2.04E-02 | 1.36E-04 | 2 |
| rs10456232 | 6 | 20579123 | 258 | 4.9 | 9.60E-07 | +++ | CDKAL1 | 2.73E-02 | 2.75E-02 | 1.49E-04 | 1 |
| Panel B: Intergenic variants; genes close to the associated markers are listed with proximal distance in base-pairs. |
| SNP | Chr | Position | Fams (MA) |
Zscore (MA) |
P-value (MA) |
Effect Direction (MA) |
Gene (proximity) | NIMH | NCRAD | NIA | Approach |
|---|---|---|---|---|---|---|---|---|---|---|---|
| rs1513625 | 2 | 101314473 | 992 | 5.479 | 4.28E-08 | ++++++ | PDCL3 (+121276) | 7.64E-03 | 1.12E-02 | 3.85E-01 | 2 |
| rs543844 | 6 | 44424800 | 968 | 5.323 | 1.02E-07 | ++++++ | CDC5L (+6637) | 3.50E-03 | 2.07E-01 | 2.63E-02 | 2 |
| rs186971130 | 2 | 104619458 | 576 | 5.311 | 1.09E-07 | ++++++ | - | 1.36E-03 | 8.69E-01 | 1.64E-02 | 2 |
| rs7374058 | 3 | 26246575 | 794 | 5.137 | 2.80E-07 | ++++++ | LINC00692 (331384) | 5.00E-02 | 2.07E-02 | 4.40E-02 | 2 |
| rs73310256 | 10 | 92438849 | 478 | 5.123 | 3.01E-07 | ++++++ | HTR7 (−61729) | 8.15E-02 | 1.25E-01 | 5.58E-02 | 2 |
| rs6908580 | 6 | 92577371 | 1058 | 5.099 | 3.41E-07 | ++++++ | - | 5.79E-03 | 2.25E-01 | 3.30E-02 | 2 |
| rs7047415 | 9 | 98541232 | 578 | 5.096 | 3.48E-07 | ++++++ | DKFZP434H0512 (+4219) | 3.73E-02 | 4.36E-01 | 3.33E-04 | 2 |
| rs982100 | 2 | 118475544 | 740 | 5.08 | 3.77E-07 | ++++++ | DDX18 (−96682) | 3.02E-02 | 5.88E-01 | 7.66E-03 | 2 |
| rs75718659 | 4 | 187743086 | 460 | 5.052 | 4.37E-07 | ++++++ | FAT1 (+95210) | 2.12E-02 | 7.51E-01 | 5.57E-01 | 2 |
| rs140633572 | 6 | 107279935 | 408 | 5.03 | 4.92E-07 | ++++++ | C6orf203 (−69472) | 1.66E-03 | 6.68E-01 | 3.68E-01 | 2 |
| rs1443024 | 2 | 185376297 | 976 | 4.999 | 5.78E-07 | ++++++ | ZNF804A (−86796) | 6.57E-02 | 4.66E-02 | 5.23E-03 | 2 |
| rs11773349 | 7 | 64407164 | 562 | 4.991 | 6.01E-07 | ++++++ | ZNF273 (+15820) | 4.69E-02 | 8.52E-01 | 1.73E-03 | 2 |
| rs36060340 | 1 | 233622928 | 766 | 4.975 | 6.54E-07 | ++++++ | MLK4 (+102034) | 1.05E-03 | 2.89E-01 | 1.88E-01 | 2 |
| rs1774093 | 9 | 104647156 | 766 | 4.956 | 7.19E-07 | ++++++ | GRIN3A (+146294) | 4.96E-03 | 6.29E-01 | 3.81E-01 | 2 |
| rs857551 | 21 | 44829992 | 588 | 4.949 | 7.45E-07 | ++++++ | SIK1 (−4403) | 3.89E-03 | 5.87E-01 | 1.15E-01 | 2 |
| rs9546312 | 13 | 83746951 | 658 | 4.92 | 8.68E-07 | ++++++ | - | 6.91E-02 | 1.16E-01 | 2.61E-01 | 2 |
| rs4705644 | 5 | 113577164 | 862 | 4.905 | 9.33E-07 | ++++++ | KCNN2 (−119478) | 2.85E-05 | 6.82E-01 | 2.48E-01 | 2 |
Legend to Table 1: FBAT-GEE method was used in the analyses using affection status and age at onset as a multivariate phenotype. The p values are nominal and two-tailed for all the associated markers. Fams indicates the number of informative families contributing to the test statistic. Age of onset coding based on Wilcoxon statistic. Meta-analysis results including the imputed data sets NIMH, NIA and NCRAD. Zscore, Z-score of the test statistic (negative scores indicate under-transmission of minor allele to affected individuals). P-value = P-value derived from the meta-analysis. Thresholds to achieve genome-wide significance is 5·10−08. Effect Direction (NCRAD, NIA, NIMH), the effect direction is positive if the involved studies have the same direction compared to the first study, otherwise it's negative. The FBAT-GEE p-values of the association signal from the three individual family cohort are listed in the columns, NIMH, NCRAD and NIA. These p-values were used in meta-analysis as described in the methods. Approach indicates the kind of analysis (1) FBAT GEE Within-Family and (2) FBAT GEE Between-Family as described in the material and method section.