Table 4.

Results of the multivariate interaction analyses. The restricted maximum likelihood (ReML) estimates of ${\tau }_G^2$, ${\tau }_W^2$, ${\tau }_{G\times W}^2$ and σ², and the p-values for the interaction effects between each of the 21 candidate Alzheimer's disease (AD) risk genes and the cardiovascular disease (CVD) risk factors on hippocampal volume, using the kernel method and the alternative methods based on dimension reduction and multiple regression, are shown. p-values that survive multiple testing corrections are highlighted in bold. PCg: first principal component of the genetic data; PCw: first principal component of the CVD risk factors; RVT: rare variant test burden variable; WST: weighted sum test burden variable; FHS: the Framingham Heart Study vascular disease risk score.

Gene	Kernel method					Alternative methods
	${\tau }_G^2$	${\tau }_W^2$	${\tau }_{G\times W}^2$	σ 2	p-value	PCg × FHS	PCg × PCw	RVT × FHS	RVT × PCw	WST × FHS	WST × PCw
ABCA7	3.44E-7	3.24E-2	9.03E-4	0.286	0.479	0.138	0.253	0.215	0.183	0.291	0.258
BIN1	6.41E-4	1.66E-2	2.03E-2	0.279	0.167	0.861	0.615	0.165	0.296	0.049	0.441
CASS4	2.17E-3	3.31E-2	3.44E-7	0.284	0.492	0.522	0.889	0.971	0.565	0.742	0.838
CD2AP	3.44E-7	4.31E-2	3.44E-7	0.290	0.954	0.150	0.737	0.145	0.618	0.229	0.728
CD33	7.76E-5	4.39E-2	3.44E-7	0.289	0.845	0.196	0.245	0.807	0.543	0.734	0.807
CELF1	3.44E-7	2.74E-2	6.52E-3	0.284	0.284	0.591	0.626	0.102	0.115	0.230	0.216
CLU	1.62E-3	3.60E-2	3.44E-7	0.286	0.602	0.920	0.998	0.140	0.479	0.154	0.563
CR1	3.44E-7	7.21E-3	4.68E-2	0.273	4.85E-4	0.559	4.08E-4	0.268	0.023	0.354	0.109
DSG2	3.44E-7	3.51E-2	3.44E-7	0.286	0.566	0.232	0.135	0.823	0.367	0.617	0.202
EPHA1	3.44E-7	3.44E-7	5.12E-2	0.273	5.64E-4	0.323	0.133	0.182	0.270	0.939	0.979
FERMT2	2.05E-2	3.17E-2	5.93E-3	0.278	0.342	0.556	0.817	0.767	0.794	0.852	0.876
HLA-DRB5	3.44E-7	3.80E-2	3.44E-7	0.286	0.759	0.764	0.388	0.763	0.388	0.763	0.388
INPP5D	6.18E-4	3.44E-2	3.44E-7	0.285	0.527	0.910	0.395	0.267	0.022	0.375	0.156
MEF2C	1.74E-3	2.08E-2	1.77E-2	0.279	0.058	0.125	0.408	0.085	0.436	0.067	0.418
MS4A6A	9.32E-4	3.77E-2	3.44E-7	0.287	0.902	0.769	0.969	0.779	0.945	0.781	0.926
PICALM	1.89E-2	3.91E-2	3.44E-7	0.281	0.679	0.473	0.295	0.580	0.390	0.922	0.294
PTK2B	1.68E-3	3.25E-2	9.00E-4	0.284	0.460	0.779	0.615	0.630	0.406	0.043	0.048
REST	3.66E-2	2.11E-2	1.95E-2	0.273	0.189	0.732	0.497	0.800	0.578	0.694	0.671
SLC24A4	8.22E-3	1.64E-2	2.35E-2	0.277	0.211	0.345	0.029	0.634	0.222	0.942	0.268
SORL1	2.30E-3	4.77E-2	3.44E-7	0.290	0.919	0.663	0.521	0.129	0.481	0.126	0.455
ZCWPW1	3.44E-7	2.85E-2	3.80E-3	0.284	0.265	0.634	0.373	0.600	0.422	0.574	0.437