Table 2.
Sex-specific genome-wide association study of neuropathology-based AD traits
| Locus | CHR(POS) | SNP ID | AD traits | A1 | Female only p-value | Female only Effect size | Male only p-value | Male only Effect size | Nearest Gene Position (dis) | MAF |
|---|---|---|---|---|---|---|---|---|---|---|
| 2q14 | chr2:127,133,851 | rs4663105 | ncAD | C | 1.01 × 10–10 | − 6.47 | 7.5 × 10–4 | − 3.37 | BIN1b/intergenic (26,495) | 0.4 |
| 2q | chr2:42,953,187 | rs17030228 | Braak stage | A | 1.23 × 10–9 | − 6.08 | 0.49 | − 0.17 | AC016735.1 lncRNAsc/intergenic (48,167) | 0.012 |
| 4q27 | chr4:121,361,613 | rs77285108 | ncAD | G | 4.67 × 10–8 | 5.46 | 0.52 | − 0.65 | QRFPRc/intronic | 0.15 |
| 19q13.32 | chr19:44,908,684 | rs429358 | ncAD | C | 1.50 × 10–21 | − 9.54 | 8.65 × 10–32 | − 11.73 | APOE regiona/exonic | 0.16 |
| chr19:44,908,684 | rs429358 | Braak stage | C | 8.50 × 10–21 | − 9.35 | 1.96 × 10–34 | − 12.24 | APOE regiona/exonic | 0.16 | |
| chr19:44,908,684 | rs429358 | NP score | C | 5.65 × 10–22 | − 9.64 | 1.08 × 10–27 | − 10.91 | APOE regiona/exonic | 0.16 |
The total sample for the ncAD female case–control GWAS was 2660 (2011 case + 649 control) and male was 2366 (1676 case + 690 control) on 7,045,108 and 7,075,025 SNPs respectively. The total sample for female Braak stage GWASs and female NP score GWASs was 2660 on 7,083,498 and 61,890,055 SNPs respectively. The total sample for male Braak stage GWASs and male NP score GWASs was 2366 individuals on 7,153,692 and 6,475,237. CHR chromosome; SNP, single-nucleotide polymorphism; A1, effect allele; MAF: minor allele frequency; Effect: Z score effect of A1 allele; Significant genome-wide association P < 5 × 10−8.a: Genes have been identified as genome-wide significant in both previous clinical AD GWAS and neuropathological AD GWAS. b: Genes have been identified as genome-wide significant in previous clinical AD GWAS. c: Genes have not been identified as genome-wide significant in previous studies
ncAD neuropathology-confirmed AD