Table 2.
Summary of main findings from rare variant reports in AD.
| Study | Design | Population | Sample size | Variant/gene | MAF % (EA/AA) | OR (95% CI) | P value |
|---|---|---|---|---|---|---|---|
| Cruchaga – PLD3 (Cruchaga et al., 2014) |
Family based WES, genotyping, and targeted sequencing. | EA (genotyping) | 4998 cases, 6356 controls | V232M/rs145999145 | 0.4884/0.2497 | 2.1 (1.47–2.99) | 2.93 × 10-5 |
| European (sequencing) | 2363 cases, 2024 controls | Gene based | N/A | 2.75 (2.05–3.68) | 1.44 × 10-11 | ||
| AA (sequencing) | 130 cases, 172 controls | Gene based | N/A | 5.48 (1.77–16.92) | 1.4 × 10-3 | ||
| Jonsson – APP (Jonsson et al., 2012) | WGS, variants imputed in large cohort. | Icelandic | 71,743 chip genotyped individuals and 296,496 relatives | A637T/rs63750847 | 0.0116/ 0.0 | 5.29 | 4.78 × 10-7 |
| Kim – ADAM10 (Kim et al., 2009) | Genotyping and targeted sequencing. | EA | 400 families (995 cases, 411 controls) | rs2305421 | Not in EVS | – | 0.003 |
| Gene based | N/A | 0.0043 | |||||
| Logue – AKAP9 (Logue et al., 2014) |
Family based WGS, Genotyping. | AA | 1037 cases, 1869 controls | rs144662445 | 0.0/0.4312 | 2.75 | 0.0022 |
| rs149979685 | 0.0/0.3631 | 3.61 | 0.0022 | ||||
| Hunkapiller – UNC5C (Hunkapiller et al., 2013) | Family based WGS and WES, Genotyping. |
EA | 8050 cases, 98194 controls | T835M/rs137875858 | 0.0581/0.0227 | 2.15 (1.21–3.84) | 0.0095 |
| Medway – APOE (Medway et al., 2014) | EVS database, Genotyping. |
EA/ European | 4128 cases, 4986 controls | V236E/rs199768005 | 0.1188/0.0 | 0.1 (0.03–0.45) | 7.5 × 10-5 |
| Pottier – SORL1 (Pottier et al., 2012) | WES in EOAD | European origin | 29 cases, 1500 controls | 7/29 AD carried variants, no controls did | |||
Summary of the study designs and major findings from the discussed rare variant association studies in the AD field. WGS, whole genome sequencing; WES, whole exome sequencing; EOAD, early onset Alzheimer’s disease; EA, European American; AA, African American; MAF, minor allele frequency. MAFs taken from NHLBI’s Exome Sequencing Project (EVS, Exome Variant Server; http://evs.gs.washington.edu/EVS/, accessed September 2014).