Genome-wide association study of brain biochemical phenotypes reveals distinct genetic architecture of Alzheimer’s disease related proteins

Oatman, Stephanie R.; Reddy, Joseph S.; Quicksall, Zachary; Carrasquillo, Minerva M.; Wang, Xue; Liu, Chia-Chen; Yamazaki, Yu; Nguyen, Thuy T.; Malphrus, Kimberly; Heckman, Michael; Biswas, Kristi; Nho, Kwangsik; Baker, Matthew; Martens, Yuka A.; Zhao, Na; Kim, Jun Pyo; Risacher, Shannon L.; Rademakers, Rosa; Saykin, Andrew J.; DeTure, Michael; Murray, Melissa E.; Kanekiyo, Takahisa; Dickson, Dennis W.; Bu, Guojun; Allen, Mariet; Ertekin-Taner, Nilüfer

doi:10.1186/s13024-022-00592-2

Molecular Neurodegeneration

Table 1 Description of genome wide significant SNPs

From: Genome-wide association study of brain biochemical phenotypes reveals distinct genetic architecture of Alzheimer’s disease related proteins

	Protein	Buffer	Transf	SNP	Chr	Locus	Position Annotation	Minor Allele	N	MAF	MAF Bin	HWE-P	Additive Model			Conditional *APOE-ε*4 model			CADD Score	Regulome Rank
	Protein	Buffer	Transf	SNP	Chr	Locus	Position Annotation	Minor Allele	N	MAF	MAF Bin	HWE-P	Beta	(CI 95%)	P	Beta	(CI 95%)	P	CADD Score	Regulome Rank
Novel	Aβ40	TBS	ln	rs9890231	17	*ITGB4*	Intron *ITGB4*	G	439	0.04	LF	1.00	−1.88	(−2.52–-1.23)	2.09E-08	−1.84	(−2.47–-1.21)	2.06E-08	3.371	5
	Aβ40	TX	ln	rs77785770	5	*KCNN2*	Intron *KCNN2*	G	441	0.05	LF	0.60	0.79	(0.53–1.05)	3.12E-09	0.72	(0.47–0.97)	2.15E-08	0.977	5
	Aβ40	TX	ln	rs148028977	15	*RFX7*	Intron *RFX7*	T	441	0.02	LF	1.00	1.24	(0.83–1.64)	4.47E-09	1.1	(0.71–1.49)	6.98E-08	12.64	5
	Aβ40	TX	ln	rs116726862	3	*SLC9A9*	Intron *SLC9A9*	T	441	0.03	LF	1.00	0.95	(0.63–1.27)	1.51E-08	0.57	(0.38–0.77)	2.78E-08	3.507	3a
	Aβ40	TX	ln	rs34805055	19	*STRN4*	Intron *STRN4*	T	441	0.08	MF	1.00	0.61	(0.41–0.82)	1.15E-08	0.85	(0.54–1.16)	1.53E-07	6.379	4
	APOE	TX	sqrt	rs116580059	7	*SCIN*	Intron *SCIN*	C	439	0.03	LF	1.00	3.34	(2.20–4.48)	1.82E-08	3.38	(2.24–4.51)	1.08E-08	1.254	3a
	APOE	TX	sqrt	rs11845003	14	*NPAS3*	Intron *NPAS3*	T	439	0.02	LF	1.00	4.05	(2.66–5.44)	2.05E-08	4.04	(2.65–5.42)	1.99E-08	7.418	4
Known	Aβ40	TX	ln	rs429358	19	*APOE*	Exon *APOE*	C	441	0.4	HF	0.07	0.37	(0.25–0.48)	6.88E-10	–	–	–	0.007	4
	Aβ40	FA	ln	rs429358	19	*APOE*	Exon *APOE*	C	441	0.4	HF	0.07	0.91	(0.68–1.15)	6.75E-14	–	–	–	0.007	4
	Aβ40/42	TX	ln	rs483082	19	*APOE/APOC1*	Intergenic	T	441	0.42	HF	0.49	0.33	(0.22–0.44)	2.11E-08	0.29	(−0.08–0.66)	0.12	10.25	4
	Aβ40/42	FA	ln	rs429358	19	*APOE*	Exon *APOE*	C	441	0.4	HF	0.07	0.94	(0.72–1.16)	1.48E-15	–	–	–	0.007	4
	APOE	FA	ln	rs429358	19	*APOE*	Exon *APOE*	C	441	0.4	HF	0.07	0.49	(0.38–0.60)	4.53E-16	–	–	–	0.007	4
	APOE	TBS	sqrt	rs283815	19	*APOE/NECTIN2*	Intron *NECTIN2*	G	441	0.42	HF	0.02	−2.41	(−3.10–-1.72)	2.60E-11	−1.51	(−2.74–-0.27)	1.75E-02	1.827	7

Descriptions of top genome-wide significant (GWS) SNPs associated with each biochemical measure in N = 441 AD cases. Seven are novel and three are known. Models include an additive model adjusted for age, sex, and PC1-3, and a conditional model conditioning on APOE-ε4 (rs429358) adjusted for age, sex, and PC1-3
Transf Transformation, N Number, MAF Minor Allele Frequency, HWE-P Hardy Weinberg Equilibrium P-value, CI Confidence Interval, P P-value

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