TABLE 2.

Summary of trans sentinel variants associated with plasma protein aptamer levels in Europeans.

						Plasma		CSF		AD
Gene	Aptamer	ID	Gene Nearest Hit	Sample Size	MAF	Effect Size	p‐Value	Effect Size	p‐Value	Effect Size	p‐Value
CLU	X4542.24	chr7:137280619:C:T	PTN	2121	0.054	0.024	2.320 × 10−8	−0.021	0.661	0.004	0.830
	X24941.14	chr1:17210401:C:T	PADI1	1951	0.008	0.061	6.781 × 10−9	0.133	0.661	−0.084	0.168
		chr8:135875240:G:A	LINC02055	1987	0.002	0.120	2.042 × 10−9	N/A	N/A	0.074	0.535
GFAP	X20126.19	chr2:88954346:G:A	IGKV5‐2	1972	0.072	0.054	2.070 × 10−20	N/A	N/A	−0.004	0.823
GRN	X4992.49	chr1:109275908:C:T	SORT1	2094	0.220	−0.054	1.863 × 10−114	0.081	0.004	−0.017	0.072
		chr10:71802391:T:C	CDH23	2094	0.263	−0.020	1.951 × 10−16	0.031	0.224	0.008	0.402
NFL	X10082.251	chr19:44908684:T:C	APOE	2116	0.232	−0.138	6.342 × 10−259	−0.223	3.548 × 10−18	−1.202	1.170 × 10−881
NRGN	X18303.39	chr10:11676245:G:A	ENSG00000271046	2001	0.001	−0.372	6.808 × 10−10	0.338	0.363	0.006	0.979
SNAP‐25	X13105.7	chr14:94318281:C:T	SERPINA6	1905	0.207	0.036	4.761 × 10−22	0.156	7.413 × 10−7	0.011	0.269
TREM2	X5635.66	chr11:60254475:G:A	MS4A4A	2121	0.363	0.077	8.392 × 10−60	0.363	3.162 × 10−54	−0.086	1.654 × 10−24
	X11851.21	chr11:60254475:G:A	MS4A4A	2118	0.363	0.065	2.242 × 10−57	0.366	1.318 × 10−57	−0.086	1.654 × 10−24
	X16300.4	chr11:60254475:G:A	MS4A4A	2111	0.363	0.074	2.967 × 10−37	0.360	1.549 × 10−41	−0.086	1.654 × 10−24
VILIP‐1	X13522.20	chr5:175754615:C:A	HRH2	1934	0.004	0.125	4.207 × 10−8	0.118	0.550	−0.122	0.144
		chr8:89002721:C:T	ENSG00000253553	1970	0.032	0.044	3.509 × 10−8	0.038	0.562	0.026	0.279
		chr11:30061301:A:G	AC124657.1	1970	0.018	0.061	8.042 × 10−9	0.142	0.170	0.037	0.299

Note: This table summarizes the variants with the lowest p‐value in each prioritized trans locus derived from the plasma GWAS. For comparison, the effect size and p‐values are shown for the same variants derived from the CSF association analyses and the Bellenguez et al., 2022 AD meta‐analysis. If missing in the Bellenguez et al., 2022 summary statistics, the Schwartzentruber et al., 2021 summary statistics were used. Sections highlighted in bold are statistically significant for CSF and/or AD at a threshold of p < 5 × 10⁻⁸. A proxy variant in LD with the top variant was used for the GRN top hit chr10:71802391:T:C (chr10:71799095:A:G; r² = 1) AD summary statistics. Protein aptamer levels were log₁₀ transformed before analysis. All participants were European in ethnicity based on principal component analysis. n = 2317.

Abbreviations: AD, Alzheimer's disease; CSF, cerebrospinal fluid; GFAP, glial fibrillary acidic protein; GWAS, genome‐wide association study; LD, linkage disequilibrium; MAF, minor allele frequency; NFL, neurofilament light; NRGN, neurogranin; SNAP‐25, synaptosomal‐associated protein 25; TREM2, triggering receptor expressed on myeloid cells 2; VILIP, visinin‐like protein 1..