Abstract
Introduction African Americans’ (AAs) late-onset Alzheimer's disease (LOAD) genetic risk profile is incompletely understood. Including clinical covariates in genetic analyses using informed conditioning might improve study power. Methods We conducted a genome-wide association study (GWAS) in AAs employing informed conditioning in 1825 LOAD cases and 3784 cognitively normal controls. We derived a posterior liability conditioned on age, sex, diabetes status, current smoking status, educational attainment, and affection status, with parameters informed by external prevalence information. We assessed association between the posterior liability and a genome-wide set of single-nucleotide polymorphisms (SNPs), controlling for APOE and ABCA7, identified previously in a LOAD GWAS of AAs. Results Two SNPs at novel loci, rs112404845 (P = 3.8 × 10−8), upstream of COBL, and rs16961023 (P = 4.6 × 10−8), downstream of SLC10A2, obtained genome-wide significant evidence of association with the posterior liability. Discussion An informed conditioning approach can detect LOAD genetic associations in AAs not identified by traditional GWAS.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 119-129 |
| Number of pages | 11 |
| Journal | Alzheimer's and Dementia |
| Volume | 13 |
| Issue number | 2 |
| DOIs | |
| State | Published - Feb 1 2017 |
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Keywords
- ABCA7
- African Americans
- Age
- Alzheimer's disease
- APOE
- COBL
- Diabetes
- Education
- Genome-wide association study (GWAS)
- Informed conditioning on clinical covariates
- Resveratrol
- Sex differences
- SLC10A2
- Smoking
ASJC Scopus subject areas
- Epidemiology
- Health Policy
- Developmental Neuroscience
- Geriatrics and Gerontology
- Clinical Neurology
- Cellular and Molecular Neuroscience
- Psychiatry and Mental health
Cite this
Two novel loci, COBL and SLC10A2, for Alzheimer's disease in African Americans. / Alzheimer's Disease Genetics Consortium.
In: Alzheimer's and Dementia, Vol. 13, No. 2, 01.02.2017, p. 119-129.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Two novel loci, COBL and SLC10A2, for Alzheimer's disease in African Americans
AU - Alzheimer's Disease Genetics Consortium
AU - Mez, Jesse
AU - Chung, Jaeyoon
AU - Jun, Gyungah
AU - Kriegel, Joshua
AU - Bourlas, Alexandra P.
AU - Sherva, Richard
AU - Logue, Mark W.
AU - Barnes, Lisa L.
AU - Bennett, David A.
AU - Buxbaum, Joseph D.
AU - Byrd, Goldie S.
AU - Crane, Paul K.
AU - Ertekin-Taner, Nilüfer
AU - Evans, Denis
AU - Fallin, M. Daniele
AU - Foroud, Tatiana
AU - Goate, Alison
AU - Graff-Radford, Neill R.
AU - Hall, Kathleen S.
AU - Kamboh, M. Ilyas
AU - Kukull, Walter A.
AU - Larson, Eric B.
AU - Manly, Jennifer J.
AU - Haines, Jonathan L.
AU - Mayeux, Richard
AU - Pericak-Vance, Margaret A
AU - Schellenberg, Gerard D.
AU - Lunetta, Kathryn L.
AU - Farrer, Lindsay A.
PY - 2017/2/1
Y1 - 2017/2/1
N2 - Introduction African Americans’ (AAs) late-onset Alzheimer's disease (LOAD) genetic risk profile is incompletely understood. Including clinical covariates in genetic analyses using informed conditioning might improve study power. Methods We conducted a genome-wide association study (GWAS) in AAs employing informed conditioning in 1825 LOAD cases and 3784 cognitively normal controls. We derived a posterior liability conditioned on age, sex, diabetes status, current smoking status, educational attainment, and affection status, with parameters informed by external prevalence information. We assessed association between the posterior liability and a genome-wide set of single-nucleotide polymorphisms (SNPs), controlling for APOE and ABCA7, identified previously in a LOAD GWAS of AAs. Results Two SNPs at novel loci, rs112404845 (P = 3.8 × 10−8), upstream of COBL, and rs16961023 (P = 4.6 × 10−8), downstream of SLC10A2, obtained genome-wide significant evidence of association with the posterior liability. Discussion An informed conditioning approach can detect LOAD genetic associations in AAs not identified by traditional GWAS.
AB - Introduction African Americans’ (AAs) late-onset Alzheimer's disease (LOAD) genetic risk profile is incompletely understood. Including clinical covariates in genetic analyses using informed conditioning might improve study power. Methods We conducted a genome-wide association study (GWAS) in AAs employing informed conditioning in 1825 LOAD cases and 3784 cognitively normal controls. We derived a posterior liability conditioned on age, sex, diabetes status, current smoking status, educational attainment, and affection status, with parameters informed by external prevalence information. We assessed association between the posterior liability and a genome-wide set of single-nucleotide polymorphisms (SNPs), controlling for APOE and ABCA7, identified previously in a LOAD GWAS of AAs. Results Two SNPs at novel loci, rs112404845 (P = 3.8 × 10−8), upstream of COBL, and rs16961023 (P = 4.6 × 10−8), downstream of SLC10A2, obtained genome-wide significant evidence of association with the posterior liability. Discussion An informed conditioning approach can detect LOAD genetic associations in AAs not identified by traditional GWAS.
KW - ABCA7
KW - African Americans
KW - Age
KW - Alzheimer's disease
KW - APOE
KW - COBL
KW - Diabetes
KW - Education
KW - Genome-wide association study (GWAS)
KW - Informed conditioning on clinical covariates
KW - Resveratrol
KW - Sex differences
KW - SLC10A2
KW - Smoking
UR - http://www.scopus.com/inward/record.url?scp=85013040148&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85013040148&partnerID=8YFLogxK
U2 - 10.1016/j.jalz.2016.09.002
DO - 10.1016/j.jalz.2016.09.002
M3 - Article
C2 - 27770636
AN - SCOPUS:85013040148
VL - 13
SP - 119
EP - 129
JO - Alzheimer's and Dementia
JF - Alzheimer's and Dementia
SN - 1552-5260
IS - 2
ER -