@article{12a296801ed44aff9a4470bcf78e98c4,
title = "Two novel loci, COBL and SLC10A2, for Alzheimer's disease in African Americans",
abstract = "Introduction African Americans{\textquoteright} (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.",
keywords = "ABCA7, APOE, African Americans, Age, Alzheimer's disease, COBL, Diabetes, Education, Genome-wide association study (GWAS), Informed conditioning on clinical covariates, Resveratrol, SLC10A2, Sex differences, Smoking",
author = "{Alzheimer's Disease Genetics Consortium} and Jesse Mez and Jaeyoon Chung and Gyungah Jun and Joshua Kriegel and Bourlas, {Alexandra P.} and Richard Sherva and Logue, {Mark W.} and Barnes, {Lisa L.} and Bennett, {David A.} and Buxbaum, {Joseph D.} and Byrd, {Goldie S.} and Crane, {Paul K.} and Nil{\"u}fer Ertekin-Taner and Denis Evans and Fallin, {M. Daniele} and Tatiana Foroud and Alison Goate and Graff-Radford, {Neill R.} and Hall, {Kathleen S.} and Kamboh, {M. Ilyas} and Kukull, {Walter A.} and Larson, {Eric B.} and Manly, {Jennifer J.} and Haines, {Jonathan L.} and Richard Mayeux and Pericak-Vance, {Margaret A.} and Schellenberg, {Gerard D.} and Lunetta, {Kathryn L.} and Farrer, {Lindsay A.}",
note = "Funding Information: Additional members of the Alzheimer's Disease Genetics Consortium who Contributed to this study: Guiqing Cai, PhD, Laura B. Cantwell, MPH, Philip L. De Jager, MD, PhD, Rodney C. P. Go, PhD, Patrick Griffith, MD, Rosalyn Lang, PhD, Oscar L. Lopez, MD, Thomas O. Obisesan, MD, Towfique Raj, PhD, and Beth Dombroski, PhD. Funding support: this work has been supported by National Institute on Aging/National Institutes of Health grants K23-AG046377 (Dr Mez); R01-AG09029, R01-AG025259, P30-AG13846 (Dr Farrer); U01-AG032984, RC2-AG036528, U01-AG016976 (Dr Kukull); U24-AG026395, U24-AG026390, R01-AG037212, R37-AG015473 (Dr Mayeux); U24-AG021886 (Dr Foroud); R01-AG20688 (Dr Fallin); P50-AG005133, AG041718, AG030653 (Dr Kamboh); R01-AG019085 (Dr Haines); R01-AG1101, R01-AG030146, RC2-AG036650 (Dr Evans); P30-AG10161, R01-AG15819, R01-AG17917 (Dr Bennett); R01AG028786 (Dr Manly); R01-AG22018, P30-AG10161 (Dr Barnes); P50-AG016574, R01-AG032990, R01-NS080820 (Dr Ertekin-Taner); R01-AG027944, R01-AG028786 (Dr Pericak-Vance); P20-MD000546, R01-AG28786 (Dr Byrd); AG005138 (Dr Buxbaum); P50-AG05681, P01-AG03991, P01-AG026276 (Dr Goate); U01-AG06781 (Drs Larson and Crane); R01-AG009956, RC2-AG036650 (Dr Hall); U01-AG032984 (Dr Schellenberg); and U24-AG041689-01 (National Institute on Aging Genetics of Alzheimer's Disease Data Storage Site at the University of Pennsylvania). Publisher Copyright: {\textcopyright} 2016 the Alzheimer's Association",
year = "2017",
month = feb,
day = "1",
doi = "10.1016/j.jalz.2016.09.002",
language = "English (US)",
volume = "13",
pages = "119--129",
journal = "Alzheimer's and Dementia",
issn = "1552-5260",
publisher = "Elsevier Inc.",
number = "2",
}