Table 1.
Association of rs1466535 in LRP1 on Chromosomal Region 12q13.3 with AAA
|
Controls |
AAA |
OR (95% CI) | p value | Phet | |||
|---|---|---|---|---|---|---|---|
| N | AF | n | AF | ||||
| Genome-wide analysis | |||||||
| Discovery | 5435 | 0.63 | 1866 | 0.68 | 1.22 (1.13–1.32) | 9.99 × 10−7 | |
| Replication | |||||||
| Iceland | 27,712 | 0.58 | 452 | 0.61 | 1.12 (0.98–1.28) | 0.10 | |
| Netherlands | 2791 | 0.65 | 840 | 0.68 | 1.14 (1.02–1.28) | 0.026 | |
| Laboratory | 2184 | 0.65 | 1579 | 0.68 | 1.12 (1.02–1.23) | 0.02 | |
| Combined replication studies | 1.13 (1.06–1.19) | 0.0042 | 0.97 | ||||
| Combined discovery and replication studies | 1.16 (1.11–1.23) | 2.86 × 10−9 | 0.49 | ||||
| Follow-up studies | |||||||
| Leeds | 254 | 0.64 | 216 | 0.67 | 1.12 (0.95–1.33) | 0.38 | |
| Viborg | 196 | 0.64 | 503 | 0.66 | 1.07 (0.94–1.22) | 0.60 | |
| Otago | 430 | 0.61 | 579 | 0.66 | 1.23 (1.04–1.45) | 0.028 | |
| Copenhagen | 10,180 | 0.63 | 193 | 0.65 | 1.04 (0.96–1.12) | 0.64 | |
| Combined follow-up studies | 1.11 (1.01–1.23) | 0.04 | 0.60 | ||||
| Overall combined analysis (6228 AAA, 49,182 controls) | 1.15 (1.10–1.21) | 4.52 × 10−10 | 0.67 | ||||
Results for the genome-wide analysis, replication, and follow-up studies of the SNP rs1466535 in LRP1 associated with AAA. Allele frequencies (AF) shown are for the risk (C) allele. Association testing was performed with the Cochran-Armitage trend test (two-tailed) analysis in the discovery study corrected for a genomic inflation factor of 1.096 and the first six components of a multidimensional scaling analysis. Two-tailed Cochran-Armitage trend tests were used in the replication and follow-up studies. The genome-wide discovery study was performed comparing a pooled AAA case set from contributing centers with the WTCCC2 unscreened controls. The laboratory replication study was performed with a pooled case and control set (not all centers contributed both cases and controls to the analysis). The control samples used in the genome-wide analysis, and the studies from Iceland and Copenhagen were not screened for the presence of AAA. The combined analysis was performed by generic inverse variance weighted meta-analysis with a fixed effects model (Phet is the p value for Cochrans Q test for heterogeneity). The overall combined analysis of the discovery, replication and follow-up studies is shown in bold type.