Table 3 Four-way decomposition of the association between Poor Oral Health Problems (POHP) and brain white matter microstructural integrity (Mean fractional anisotropy across tracts, FA_mean, z-scored) through selected plasma proteomic biomarkers (k = 15; N_max = 5089): UK biobank 2006–2021.

From: Mediating and moderating effects of plasma proteomic biomarkers on the association between poor oral health problems and brain white matter microstructural integrity: the UK Biobank study

FOURWAYDECOMP	Beta	SE	z	P	LCL	UCL	PROTEIN
te	−0.1378	0.04379	−3.15	0.002	−0.2236	−0.0519	odam
cde	−0.1329	0.04467	−2.98	0.003	−0.2205	−0.0454	odam
intref	0.00116	0.00126	0.92	0.355	−0.0013	0.00364	odam
intmed	−0.01081	0.01063	−1.02	0.309	−0.0316	0.01001	odam
pie	0.00485	0.00431	1.13	0.26	−0.0036	0.0133	odam
pct_cde	96.5						odam
pct_intref	−0.85						odam
pct_intmed	7.85						odam
pct_pie	−3.52						odam
te	−0.1420	0.0439	−3.24	0.001	−0.2280	−0.0560	efna4
cde	−0.1425	0.0453	−3.15	0.002	−0.2313	−0.0537	efna4
intref	−0.0003	0.0010	−0.29	0.773	−0.0022	0.0017	efna4
intmed	0.0027	0.0092	0.29	0.771	−0.0153	0.0207	efna4
pie	−0.0019	0.0037	−0.50	0.616	−0.0092	0.0055	efna4
pct_cde	100.36						efna4
pct_intref	0.21						efna4
pct_intmed	−1.88						efna4
pct_pie	1.32						efna4
te	−0.1330	0.0442	−3.01	0.003	−0.2196	−0.0464	acvrl1
cde	−0.1275	0.0458	−2.78	0.005	−0.2174	−0.0377	acvrl1
intref	0.0010	0.0011	0.88	0.378	−0.0012	0.0031	acvrl1
intmed	−0.0090	0.0089	−1.01	0.315	−0.0265	0.0085	acvrl1
pie	0.0025	0.0034	0.74	0.462	−0.0042	0.0092	acvrl1
pct_cde	95.87						acvrl1
pct_intref	−0.73						acvrl1
pct_intmed	6.75						acvrl1
pct_pie	−1.89						acvrl1
te	−0.1137	0.0445	−2.56	0.011	−0.2010	−0.0265	gdf15
cde	−0.0949	0.0466	−2.04	0.042	−0.1863	−0.0036	gdf15
intref	0.0013	0.0012	1.08	0.28	−0.0011	0.0036	gdf15
intmed	−0.0118	0.0087	−1.36	0.175	−0.0288	0.0052	gdf15
pie	−0.0083	0.0035	−2.35	0.019	−0.0152	−0.0014	gdf15
pct_cde	83.49						gdf15
pct_intref	−1.13						gdf15
pct_intmed	10.36						gdf15
pct_pie	7.29						gdf15
te	−0.1245	0.0431	−2.89	0.004	−0.2090	−0.0400	ren
cde	−0.1121	0.0438	−2.56	0.011	−0.1979	−0.0262	ren
intref	0.0015	0.0012	1.18	0.236	−0.0009	0.0039	ren
intmed	−0.0132	0.0083	−1.59	0.112	−0.0296	0.0031	ren
pie	−0.0007	0.0032	−0.21	0.832	−0.0070	0.0057	ren
pct_cde	90.00						ren
pct_intref	−1.17						ren
pct_intmed	10.62						ren
pct_pie	0.55						ren
te	−0.1227	0.0436	−2.81	0.005	−0.2081	−0.0372	tnfrsf1a
cde	−0.1178	0.0448	−2.63	0.009	−0.2056	−0.0299	tnfrsf1a
intref	0.0004	0.0009	0.42	0.673	−0.0013	0.0020	tnfrsf1a
intmed	−0.0033	0.0075	−0.44	0.662	−0.0180	0.0115	tnfrsf1a
pie	−0.0020	0.0030	−0.66	0.507	−0.0078	0.0038	tnfrsf1a
pct_cde	96.01						tnfrsf1a
pct_intref	−0.29						tnfrsf1a
pct_intmed	2.68						tnfrsf1a
pct_pie	1.60						tnfrsf1a
te	−0.1290	0.0431	−3	0.003	−0.2134	−0.0446	tnfrsf4
cde	−0.1268	0.0438	−2.9	0.004	−0.2126	−0.0410	tnfrsf4
intref	0.0011	0.0010	1.04	0.297	−0.0009	0.0031	tnfrsf4
intmed	−0.0099	0.0072	−1.37	0.17	−0.0240	0.0042	tnfrsf4
pie	0.0066	0.0033	1.99	0.046	0.0001	0.0131	tnfrsf4
pct_cde	98.32						tnfrsf4
pct_intref	−0.84						tnfrsf4
pct_intmed	7.66						tnfrsf4
pct_pie	−5.14						tnfrsf4
te	−0.1231	0.0436	−2.82	0.005	−0.2085	−0.0376	vsig4
cde	−0.1168	0.0448	−2.61	0.009	−0.2046	−0.0291	vsig4
intref	0.0004	0.0009	0.43	0.665	−0.0013	0.0020	vsig4
intmed	−0.0034	0.0075	−0.45	0.653	−0.0181	0.0114	vsig4
pie	−0.0032	0.0030	−1.08	0.281	−0.0091	0.0027	vsig4
pct_cde	94.92						vsig4
pct_intref	−0.30						vsig4
pct_intmed	2.75						vsig4
pct_pie	2.63						vsig4
te	−0.1302	0.0435	−2.99	0.003	−0.2155	−0.0450	cd83
cde	−0.1241	0.0443	−2.8	0.005	−0.2110	−0.0373	cd83
intref	0.0010	0.0010	0.93	0.352	−0.0011	0.0030	cd83
intmed	−0.0088	0.0077	−1.15	0.249	−0.0238	0.0062	cd83
pie	0.0018	0.0029	0.6	0.547	−0.0040	0.0075	cd83
pct_cde	95.32						cd83
pct_intref	−0.74						cd83
pct_intmed	6.77						cd83
pct_pie	−1.35						cd83
te	−0.1325	0.0454	−2.92	0.004	−0.2215	−0.0436	wfdc2
cde	−0.1218	0.0466	−2.61	0.009	−0.2132	−0.0304	wfdc2
intref	0.0000	0.0008	0.02	0.987	−0.0015	0.0016	wfdc2
intmed	−0.0001	0.0073	−0.02	0.987	−0.0144	0.0141	wfdc2
pie	−0.0106	0.0039	−2.7	0.007	−0.0183	−0.0029	wfdc2
pct_cde	91.90						wfdc2
pct_intref	−0.01						wfdc2
pct_intmed	0.09						wfdc2
pct_pie	8.02						wfdc2
te	−0.1386	0.0430	−3.23	0.001	−0.2229	−0.0544	il2ra
cde	−0.1363	0.0437	−3.12	0.002	−0.2221	−0.0506	il2ra
intref	−0.0003	0.0008	−0.38	0.706	−0.0019	0.0013	il2ra
intmed	0.0027	0.0070	0.39	0.697	−0.0110	0.0165	il2ra
pie	−0.0047	0.0031	−1.55	0.121	−0.0107	0.0013	il2ra
pct_cde	98.34						il2ra
pct_intref	0.22						il2ra
pct_intmed	−1.98						il2ra
pct_pie	3.42						il2ra
te	−0.1387	0.0441	−3.15	0.002	−0.2250	−0.0524	tnfrsf10b
cde	−0.1337	0.0452	−2.96	0.003	−0.2224	−0.0451	tnfrsf10b
intref	0.0000	0.0008	−0.05	0.96	−0.0015	0.0015	tnfrsf10b
intmed	0.0004	0.0071	0.05	0.96	−0.0136	0.0143	tnfrsf10b
pie	−0.0053	0.0031	−1.69	0.091	−0.0114	0.0008	tnfrsf10b
pct_cde	96.42						tnfrsf10b
pct_intref	0.03						tnfrsf10b
pct_intmed	−0.26						tnfrsf10b
pct_pie	3.81						tnfrsf10b
te	−0.1238	0.0442	−2.8	0.005	−0.2103	−0.0372	colec12
cde	−0.1229	0.0457	−2.69	0.007	−0.2124	−0.0334	colec12
intref	0.0002	0.0008	0.27	0.784	−0.0014	0.0018	colec12
intmed	−0.0020	0.0073	−0.28	0.78	−0.0164	0.0123	colec12
pie	0.0010	0.0028	0.35	0.729	−0.0045	0.0065	colec12
pct_cde	99.31						colec12
pct_intref	−0.18						colec12
pct_intmed	1.65						colec12
pct_pie	−0.78						colec12
te	−0.1272	0.0435	−2.93	0.003	−0.2124	−0.0420	relt
cde	−0.1293	0.0445	−2.91	0.004	−0.2165	−0.0422	relt
intref	−0.0002	0.0007	−0.31	0.755	−0.0017	0.0012	relt
intmed	0.0021	0.0067	0.32	0.75	−0.0110	0.0152	relt
pie	0.0002	0.0028	0.09	0.93	−0.0052	0.0057	relt
pct_cde	101.69						relt
pct_intref	0.18						relt
pct_intmed	−1.68						relt
pct_pie	−0.19						relt
te	−0.1122	0.0437	−2.57	0.01	−0.1977	−0.0266	plaur
cde	−0.1014	0.0447	−2.27	0.023	−0.1891	−0.0138	plaur
intref	0.0010	0.0011	0.93	0.352	−0.0011	0.0032	plaur
intmed	−0.0094	0.0080	−1.18	0.237	−0.0250	0.0062	plaur
pie	−0.0023	0.0028	−0.84	0.403	−0.0078	0.0031	plaur
pct_cde	90.44						plaur
pct_intref	−0.91						plaur
pct_intmed	8.39						plaur
pct_pie	2.08						plaur

Tereri and ereri_cde are interpreted as difference in FA z-score between POHP+ and POHP- groups. Models were adjusted for baseline age, sex, race/ethnicity, household size, SES z-score and LE8 total score. Names of the genes/proteins can be found at: https://www.ncbi.nlm.nih.gov/gene.
ereri_cde excess relative risk due to neither mediation nor interaction or controlled direct effect, ereri_intmed excess relative risk due to mediated interaction or mediated interaction, ereri_intref excess relative risk due to interaction only or interaction referent, ereri_pie excess relative risk due to mediation only or pure indirect effect, FA Fractional Anisotropy, LE8 Life’s Essential 8, pct_cde percent of total effect that is controlled direct effect, pct_intmed percent of total effect that is mediated interaction, pct_intref percent of total effect that is interaction referent, pct_pie percent of total effect that is pure indirect effect, Pd Periodontal Disease, POHP Poor Oral Health Problems, tereri Total excess relative risk, UK United Kingdom.

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Table 3 Four-way decomposition of the association between Poor Oral Health Problems (POHP) and brain white matter microstructural integrity (Mean fractional anisotropy across tracts, FA_mean, z-scored) through selected plasma proteomic biomarkers (k = 15; N_max = 5089): UK biobank 2006–2021.

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