TABLE 2.

Top differences in co‐skewness between Alzheimer's disease (AD) affected and unaffected subjects ranked using two metrics

ID	Rp‐val	RΔG	SNP1	SNP2	SNP3	E4	E2	$G_{1case}^h$	$G_{1nc}^h$	$\mathrm{\Delta }{G}_1^h$	p_value	$G_{1case}^{h,m}$	$G_{1nc}^{h,m}$	$G_{1case}^{h,pw}$	$G_{1nc}^{h,pw}$
4922	1	1	rs2075650	rs429358	rs12721046	e4	no	0.414	1.112	–0.698	7.38E‐178	0.439	0.276	–0.025	0.836
4895	2	12	rs157580	rs440446	rs429358	e4	no	0.258	0.058	0.199	1.24E‐167	–0.551	–0.267	0.809	0.325
4952	3		rs440446	rs429358	rs439401	e4	no	0.222	0.044	0.178	3.70E‐148	0.210	–0.285	0.012	0.329
4956	4		rs440446	rs439401	rs12721046	no	no	0.195	0.043	0.151	2.00E‐127	–0.511	–0.290	0.706	0.333
4921	5	18	rs2075650	rs429358	rs439401	e4	no	0.155	0.347	–0.192	5.05E‐124	–0.501	–0.552	0.656	0.899
4898	6		rs157580	rs440446	rs12721046	no	no	0.229	0.058	0.171	2.32E‐123	–0.494	–0.270	0.724	0.328
4900	7		rs157580	rs429358	rs439401	e4	no	–0.155	0.006	–0.161	4.35E‐119	–0.212	–0.174	0.057	0.179
4937	8	7	rs8106922	rs429358	rs12721046	e4	no	0.174	0.383	–0.209	8.96E‐115	0.251	0.086	–0.078	0.297
4907	9	5	rs2075650	rs8106922	rs429358	e4	no	0.118	0.336	–0.218	3.88E‐105	0.249	0.085	–0.132	0.251
4932	10		rs8106922	rs440446	rs7412	no	e2	0.106	0.249	–0.143	1.01E‐104	0.130	0.193	–0.024	0.057
4880	11	6	rs157580	rs2075650	rs429358	e4	no	0.108	0.325	–0.217	2.87E‐102	–0.382	–0.557	0.490	0.882
4904	12		rs157580	rs439401	rs12721046	no	no	–0.139	0.008	–0.146	2.87E‐98	0.509	0.275	–0.648	–0.267
4947	13	19	rs405509	rs429358	rs12721046	e4	no	0.334	0.525	–0.191	3.08E‐93	0.326	0.119	0.008	0.406
4920	14		rs2075650	rs429358	rs7412	e4	e2	0.031	0.120	–0.088	1.42E‐89	–0.159	–0.213	0.190	0.332
4959	15	11	rs429358	rs439401	rs12721046	e4	no	0.116	0.317	–0.201	2.85E‐89	0.243	0.088	–0.127	0.229
4916	16		rs2075650	rs440446	rs429358	e4	no	0.161	0.347	–0.187	2.99E‐88	0.233	0.084	–0.072	0.264
4953	17	13	rs440446	rs429358	rs12721046	e4	no	0.105	0.303	–0.198	4.15E‐76	–0.479	–0.523	0.585	0.826
4901	18	8	rs157580	rs429358	rs12721046	e4	no	0.108	0.315	–0.207	4.61E‐75	–0.476	–0.547	0.583	0.862
4958	19		rs429358	rs7412	rs12721046	e4	e2	0.036	0.121	–0.085	1.31E‐69	–0.126	–0.205	0.162	0.326
4938	20		rs8106922	rs7412	rs439401	no	e2	0.084	0.199	–0.115	6.53E‐69	0.135	–0.132	–0.051	0.331
4019		2	rs17561351	rs4081918	rs405509	no	no	0.102	0.380	–0.278	1.59E‐15	0.680	0.542	–0.579	–0.162
4015		3	rs17561351	rs4081918	rs283813	no	no	0.270	0.014	0.255	1.27E‐09	0.182	0.162	0.087	–0.147
4897		4	rs157580	rs440446	rs439401	no	no	0.457	0.222	0.235	6.72E‐53	–1.114	–0.865	1.571	1.087
1361		9	rs10402271	rs4803763	rs3852856	no	no	0.151	0.354	–0.203	1.82E‐30	–1.231	–1.152	1.382	1.506
4422		10	rs519113	rs387976	rs405509	no	no	0.036	0.239	–0.203	1.74E‐26	0.494	0.413	–0.458	–0.174
4012		14	rs17561351	rs4081918	rs11667640	no	no	1.397	1.595	–0.198	9.75E‐04	0.145	0.155	1.252	1.440
4912		15	rs2075650	rs405509	rs429358	e4	no	0.271	0.467	–0.196	2.06E‐61	0.309	0.107	–0.038	0.360
4771		16	rs6859	rs2075650	rs429358	e4	no	0.172	0.367	–0.195	1.18E‐23	–0.600	–0.805	0.772	1.172
4915		17	rs2075650	rs405509	rs12721046	no	no	0.268	0.461	–0.193	3.76E‐62	0.288	0.114	–0.020	0.347
2657		20	rs4803763	rs429358	rs12721046	e4	no	0.110	0.301	–0.191	4.71E‐16	0.406	0.292	–0.295	0.009

The data are from the pooled sample of the National Institute on Aging Late‐Onset Alzheimer's Disease Family Study, the Health and Retirement Study, the Cardiovascular Health Study, and the Framingham Heart Study parental and offspring cohorts.

ID in this column corresponds to IDs in Table S3.

R_p‐val and R_ΔG show ranking based on P‐value and effect size, respectively. Blank cells indicate ranking outside of top 20 triples for each metric.

E4 or E2 indicates presence of the APOE ε4‐coding rs429358 SNP or ε2‐coding rs7412 SNP in the triple.

$\mathrm{\Delta }{G}_1^h=G_{1case}^h-G_{1nc}^h$ is the effect defined as difference in co‐skewness between the AD‐affected ($G_{1case}^h$) and unaffected ($G_{1nc}^h$) subjects using the haplotype‐based method.

$G_1^{h,m}$ and $G_1^{h,pw}$ denote partitions of the $G_{1case}^h$ and $G_{1nc}^h$ metrics into two fractions of mutual independence ($G_1^{h,m}$) and a weighted sum of the pairwise linkage disequilibrium ($G_1^{h,pw}$) values (see Methods).

Italic shows SNPs from the NECTIN2 gene. Underlining denotes BCAM SNP. The other SNPs are in the TOMM40‐APOE‐APOC1 locus (see more details in Table S3).