Polygenic effects on the risk of Alzheimer’s disease in the Japanese population

Kikuchi, Masataka; Miyashita, Akinori; Hara, Norikazu; Kasuga, Kensaku; Saito, Yuko; Murayama, Shigeo; Kakita, Akiyoshi; Akatsu, Hiroyasu; Ozaki, Kouichi; Niida, Shumpei; Kuwano, Ryozo; Iwatsubo, Takeshi; Nakaya, Akihiro; Ikeuchi, Takeshi

doi:10.1186/s13195-024-01414-x

Alzheimer's Research & Therapy

Table 4 Associations between PRS and AD-related phenotypes

From: Polygenic effects on the risk of Alzheimer’s disease in the Japanese population

	Model 1 (Age, Sex, Education, PC1, PC2)		Model 2 (Age, Sex, Education, PC1, PC2, APOEε4)		Model 3 (Age, Sex, Education, PC1, PC2, APOEε4, APOEε2)
	Beta (noAPOE, adjLD)	p value (noAPOE, adjLD)	Beta (noAPOE, adjLD)	p value (noAPOE, adjLD)	Beta (noAPOE, adjLD)	p value (noAPOE, adjLD)
4a CSF biomarker
	All subjects
tTau/Aβ42	0.167, 0.159	0.017^a, 0.017^a	0.149, 0.146	0.058, 0.053	0.163, 0.156	0.040^a, 0.039^a
pTau/Aβ42	0.200, 0.168	0.004^b, 0.011^b	0.188, 0.154	0.013^a, 0.033^a	0.189, 0.155	0.013^a, 0.032^a
	CU subjects
tTau/Aβ42	-0.082, 0.204	0.804, 0.522	-0.050, 0.265	0.888, 0.435	-0.131, 0.194	0.717, 0.579
pTau/Aβ42	-0.143, -0.010	0.488, 0.960	-0.134, 0.014	0.545, 0.948	-0.178, -0.029	0.430, 0.895
	MCI subjects
tTau/Aβ42	0.292, 0.277	0.025^a, 0.032^a	0.294, 0.290	0.043^a, 0.043^a	0.295, 0.292	0.044^a, 0.044^a
pTau/Aβ42	0.363, 0.318	0.004^b, 0.011^a	0.396, 0.355	0.006^a, 0.013^a	0.396, 0.357	0.007^a, 0.014^a
	ADD patients
tTau/Aβ42	-0.054, -0.042	0.665, 0.703	-0.053, -0.043	0.682, 0.703	0.026, 0.006	0.854, 0.959
pTau/Aβ42	0.066, 0.018	0.577, 0.866	0.070, 0.019	0.565, 0.862	0.084, 0.028	0.485, 0.796
4b Brain volume
	All subjects
Entorhinal	-0.014, -0.024	0.776, 0.622	-0.008, -0.018	0.869, 0.714	-0.010, -0.019	0.836, 0.699
Hippocampus	-0.109, -0.115	0.042, 0.033	-0.101, -0.106	0.087, 0.073	-0.101, -0.106	0.088, 0.073
	CU subjects
Entorhinal	0.032, 0.024	0.512, 0.626	0.033, 0.024	0.509, 0.626	0.036, 0.033	0.495, 0.529
Hippocampus	0.041, -0.010	0.758, 0.943	0.041, -0.010	0.760, 0.942	0.043, -0.016	0.754, 0.908
	MCI subjects
Entorhinal	-0.355, -0.357	0.150, 0.156	-0.335, -0.344	0.180, 0.176	-0.332, -0.341	0.184, 0.180
Hippocampus	-0.064, -0.082	0.505, 0.407	-0.041, -0.071	0.694, 0.505	-0.043, -0.073	0.684, 0.497
	ADD patients
Entorhinal	0.108, -0.078	0.745, 0.811	0.084, -0.089	0.801, 0.788	0.112, -0.070	0.739, 0.832
Hippocampus	-0.043, -0.055	0.755, 0.688	-0.080, -0.072	0.574, 0.609	-0.069, -0.064	0.633, 0.652
4c PET imaging
	All subjects
FDG (positive)	0.180, 0.193	0.189, 0.149	0.162, 0.174	0.260, 0.218	0.162, 0.172	0.262, 0.224
PiB (positive)	0.386, 0.359	0.024^a, 0.030	0.446, 0.417	0.025^a, 0.030	0.442, 0.412	0.027, 0.033
	CU subjects
FDG (positive)	-0.119, -0.070	0.729, 0.839	-0.109, -0.064	0.753, 0.852	-0.109, -0.061	0.755, 0.860
PiB (positive)	0.037, 0.068	0.923, 0.858	0.072, 0.221	0.874, 0.620	0.059, 0.194	0.899, 0.671
	MCI subjects
FDG (positive)	0.020, 0.053	0.942, 0.845	0.038, 0.077	0.892, 0.787	0.040, 0.076	0.888, 0.791
PiB (positive)	0.201, 0.175	0.489, 0.552	0.299, 0.320	0.432, 0.407	0.303, 0.327	0.433, 0.405
	ADD patients
FDG (positive)	-0.395, -0.232	0.357, 0.542	-0.390, -0.232	0.366, 0.545	-0.352, -0.195	0.417, 0.611
PiB (positive)	-0.716, -0.777	0.313, 0.196	-0.747, -0.935	0.314, 0.133	-0.716, -0.915	0.338, 0.146
4d Neuropsychological test
	All subjects
ADAS	0.171, 0.127	0.001^b, 0.008^b	0.163, 0.117	0.002^b, 0.019^a	0.164, 0.116	0.002^b, 0.019^a
CDRSB	0.188, 0.167	6.29 × 10^−5b, 0.001^b	0.182, 0.160	1.78 × 10^−4b, 0.003^b	0.182, 0.160	1.84 × 10^−4b, 0.003^b
FAQ	0.166, 0.168	3.93 × 10^−4b, 3.58 × 10^−4b	0.159, 0.161	0.001^b, 0.001^b	0.159, 0.161	0.001^b, 0.001^b
MMSE	-0.160, -0.149	0.001^b, 0.002^b	-0.152, -0.141	0.002^b, 0.005^b	-0.152, -0.141	0.002^b, 0.005^b
	CU subjects
ADAS	-0.118, 0.045	0.592, 0.837	-0.119, 0.045	0.591, 0.837	-0.111, 0.057	0.617, 0.795
CDRSB	-1.178, -0.835	0.152, 0.305	-1.208, -0.883	0.152, 0.290	-1.217, -0.896	0.150, 0.284
FAQ	0.291, 0.359	0.473, 0.368	0.294, 0.359	0.470, 0.369	0.287, 0.349	0.483, 0.385
MMSE	-0.153, -0.228	0.454, 0.258	-0.153, -0.229	0.459, 0.258	-0.140, -0.212	0.503, 0.303
	MCI subjects
ADAS	0.194, 0.193	0.098, 0.107	0.176, 0.185	0.147, 0.136	0.182, 0.192	0.133, 0.123
CDRSB	0.146, 0.162	0.289, 0.251	0.144, 0.160	0.297, 0.256	0.149, 0.166	0.280, 0.241
FAQ	0.119, 0.145	0.239, 0.161	0.121, 0.146	0.233, 0.159	0.118, 0.143	0.246, 0.168
MMSE	-0.065, -0.062	0.604, 0.626	-0.055, -0.056	0.661, 0.664	-0.045, -0.046	0.720, 0.722
	ADD patients
ADAS	-0.048, -0.026	0.719, 0.844	-0.057, -0.029	0.671, 0.824	-0.057, -0.029	0.672, 0.826
CDRSB	0.102, 0.063	0.290, 0.501	0.109, 0.066	0.260, 0.485	0.097, 0.060	0.318, 0.528
FAQ	0.078, 0.056	0.327, 0.472	0.093, 0.062	0.248, 0.430	0.088, 0.060	0.275, 0.450
MMSE	0.036, 0.045	0.794, 0.734	0.031, 0.044	0.823, 0.746	0.033, 0.045	0.810, 0.740

β estimates and p value were calculated by a linear regression model. P value was corrected in each subject group. Statistically significance was highlighted in bold
^aFDR < 0.05
^bFDR < 0.01

Back to article page

ISSN: 1758-9193

Contact us

General enquiries: journalsubmissions@springernature.com