Table 4.

Influence of Single SNP and a Cumulative Genetic Risk Score on Clinical Diagnosis^a,^b

SNP	Gene	OR (95% CI)	P Value	FDR-Corrected P Value
APOE locus ε4	APOE (ε4)	2.07 (1.67–2.56)	<1 × 10−6	<1 × 10−6
Validated loci
rs11136000	CLU	0.97 (0.80–1.17)	.75	.76
rs3851179	PICALM	0.99 (0.81–1.20)	.87	.88
rs1408077	CR1	1.27 (1.03–1.63)	.02	.02
Novel candidate loci
rs10501927	CNTN5	1.25 (1.02–1.53)	.03	.03
rs7561528	BIN1	1.29 (1.03–1.62)	.03	.03
Genetic risk score (cumulative effect)
Genetic risk score quartiles		1.14 (1.04–1.25)	.001	.001

Abbreviations: CI, confidence interval; FDR, false discovery rate; OR, odds ratio; SNP, single-nucleotide polymorphism.

^aSNPs were selected based on results of prior genome-wide association studies⁴,⁵ with P < 1 × 10⁻⁵. Results are not shown for 11 SNPs at novel candidate loci with P > .05. The genetic risk score includes all (5 of 16) SNPs outside the APOE locus achieving P < .05 in ordinal logistic regression. All analyses are adjusted for age, sex, history of hypertension, education level (<13, 13–16, or >16 years), alcohol abuse, smoking (ever smoker status), and principal components 1 and 2. Analyses for SNPs outside the APOE locus were also adjusted for APOE genotypes (number of ε2 and ε4 copies).

^bClinical diagnosis defined as cognitively normal controls, mild cognitive impairment not converted to Alzheimer disease, mild cognitive impairment conversion to Alzheimer disease, and Alzheimer disease.