Rare TREM2 variants associated with Alzheimer’s disease display reduced cell surface expression

Table 2 Aggregate variant burden analysis in discovery and replication cohorts

Cohort	Gene	Testable SNPs	SNPs tested	MAC	P-value	Corrected P-value
Discovery (UCSF)	*TREM2*	19	8	10	1.00×10 ⁻³	0.04
	SMG6	38	4	4	3.42×10⁻²	NS
	ARHGAP27	17	4	6	0.1	NS
	HSPA6	18	6	9	0.15	NS
	LRRK2	46	9	10	0.16	NS
	WDR81	28	10	12	0.2	NS
	PLCD3	16	4	5	0.2	NS
	MAP1B	28	7	9	0.22	NS
	UBAP1	11	4	4	0.22	NS
	NPEPPS	11	4	6	0.23	NS
Replication (ADSP)	*TREM2*	41	24	330	2.88×10 ⁻⁴	0.02
	GYPC	24	16	31	5.19×10⁻³	NS
	UBAP2	123	72	207	0.05	NS
	PACRG	20	14	93	0.06	NS
	ZNF621	32	17	24	0.06	NS
	EPHX2	56	38	284	0.08	NS
	RPIA	28	9	11	0.09	NS
	FYN	28	13	43	0.1	NS
	HSPA6	25	20	89	0.11	NS
	HSPA4	59	28	183	0.12	NS
Replication (ADSP - Pathology Confirmed)	*TREM2*	41	16	192	2.11×10 ⁻⁴	0.01
	CLU	51	19	108	2.78×10⁻³	NS
	KIF24	136	54	243	6.00×10⁻³	NS
	GYPC	24	8	12	0.02	NS
	BIN1	61	16	41	0.03	NS
	RNF19A	56	23	48	0.03	NS
	MR1	43	18	106	0.04	NS
	EPHX2	56	29	181	0.06	NS
	RPIA	28	7	9	0.09	NS
	PACRG	20	12	58	0.09	NS

Results from discovery and replication burden analyses in SKAT. Genes in bold were significant after multiple testing correction. SNP single nucleotide polymorphism, MAC minor allele count, NS not significant

ISSN: 2051-5960