Table 3.

Summary of current rare variant (MAF ≤ 0.01) AD genomics findings from the GWAS by Jansen et al (14) and Kunkle et al (16)

Chr	Pos	LeadSNP	A1 vs. A2	MAF‡	P‐value Jansen	P‐value Kunkle	AD effect	Nearest gene	AD pathway	Potential link to AD pathogenesis
3	57226150	rs184384746	T vs. C	0.002	1.24E‐08	n.a.	Risk	HESX1	None	Homoebox Gene; Development
6	41129252	rs75932628	T vs. C	0.002	2.95E‐15	2.95E‐12*	Risk	TREM2	Immune system response	Innate Immunity; neuroinflammation
7	145950029	rs114360492	T vs. C	0.0003	2.10E‐09	n.a.	RISK	CNTNAP2	None	Neuronal Development
16†	81942028	rs72824905	G vs. C	0.01	2.11E‐03	7.92E‐03*	Protection	PLCG2	None	Microglial activation; neuroinflammation
17†	47297297	rs616338	T vs. C	0.01	7.81E‐07	n.a.	Risk	ABI3	None	Microglial activation; neuroinflammation

“Chr,” “Pos,” “A1 vs. A2,” “AD effect” taken from Jansen et al. “Nearest gene” determined from UCSC genome browser (GRCh37; hg19).

Blue highlight indicates “novel” AD locus in GWAS by Jansen et al, grey highlight indicates “novel” AD locus in GWAS by Kunkle et al, no highlight indicates previously described GWAS findings.

AD pathway as determined in either or both GWAS: “immune” = “immune system response”; “lipid” = “lipid metabolism”, “APP” = “APP metabolism”, “tau” = “tau protein binding” (see text for more details).

“Potential link to AD pathogenesis” = based on the authors' review (and interpretation) of the literature.

^*Stage 1 result from Kunkle et al.

^**Stage 2 result from Kunkle et al.

^***Stage 3 result from Kunkle et al.

^†Variants in PLCG2, and ABI3 were highlighted in a rare variant GWAS by the IGAP group (Sims et al, 2018) (20) published prior to the Kunkle et al, 2019 (16) study and are listed here for reasons of completeness.

^‡MAF = minor allele frequency; from European controls (non‐Finnish) as provided on GnomAD [v.2.1.1.; https://gnomad.broadinstitute.org/].