Neuroimaging Measures as Endophenotypes in Alzheimer's Disease

Table 2

SNPs with AD-relevant effects detected by neuroimaging measures.

Neuroimaging measure	SNP	Gene	Location^c	Neuroimaging association
Hippocampal volume or gray matter density	rs429358/rs7412 (ε2/3/4)^b	APOE	19q13.32	CG [47], GWA [104]
	rs10501927	CNTN5	11q22.1	CG [47]
	rs3851179^b	PICALM	11q14.2	CG [47]
	rs4646994^b	ACE	17q23.3	CG [68]
	rs2075650^b	TOMM40	19q13.32	GWA [104]
	rs4692256	LOC391642	4p15.1	GWA [104]
	rs10074258^b	EFNA5	5q21.3	GWA [108]
	rs12654281^b	EFNA5	5q21.3	GWA [108]
	rs10781380	PRUNE2	9q21.2	GWA [108]
	rs1888414	FDPSP	21q21.1	GWA [108]
ERC thickness	rs429358/rs7412 (𝜀2/3/4)^b	APOE	19q13.32	CG [47]
	rs3851179^b	PICALM	11q14.2	CG [47]
	rs10501927	CNTN5	11q22.1	CG [47]
	rs1408077^b	CR1	1q32.2	CG [47]
	rs7561528^b	BIN1	2q14.3	CG [47]
PHG cortical thickness	rs429358/rs7412 (𝜀2/3/4)^b	APOE	19q13.32	CG [47]
	rs10501927	CNTN5	11q22.1	CG [47]
Amygdala volume	rs429358/rs7412 (𝜀2/3/4)^b	APOE	19q13.32	CG [47], GWA [104]
	rs2075650^b	TOMM40	19q13.32	GWA [104]
	rs4646994^b	ACE	17q23.3	CG [68]
MTL volume	rs4935775^b	SORL1	11q24.1	CG [58]
Temporal pole cortical thickness	rs429358/rs7412 (𝜀2/3/4)^b	APOE	19q13.32	CG [47]
	rs10501927	CNTN5	11q22.1	CG [47]
	rs7561528^b	BIN1	2q14.3	CG [47]
Temporal lobe volume	rs429368/rs7412 (𝜀2/3/4)^b	APOE	19q13.32	GWA [81]
	rs10845840	GRIN2B	12p13.1	GWA [81]
	rs2456930	chromosome 15 intergenic region	15q22.2	GWA [81]
Frontal lobe volume	rs3751812	FTO	16q12.2	CG[76]
GM density-precuneus	rs10932886	EPHA4	2q36.1	GWA [104]
GM density-frontal cortex	rs10932886	EPHA4	2q36.1	GWA [104]
	rs6463843	NXPH1	7p21.3	GWA [104]
Regional brain tissue volume in temporal lobe	rs2429582	CADPS2	7q31.32	vGWA [113]
Regional brain tissue volume in parietal lobe	rs476463	CSMD2	1p35.1	vGWA [113]
Whole brain volume	rs1468063^b	FAS	10q23.31	CG [71]
Ventricular volume	rs1468063^b	FAS	10q23.31	CG [71]
WM lesion volume^a	rs10501927	CNTN5	11q22.1	CG [47]
	rs560573^b	SORL1	11q24.1	CG [58]
	rs668387^b	SORL1	11q24.1	CG [58]
	rs689021^b	SORL1	11q24.1	CG [58]
	rs641120^b	SORL1	11q24.1	CG [58]
	rs2276346^b	SORL1	11q24.1	CG [58]
	rs4646994^b	ACE	17q23	CG [65]
WM integrity^a	rs11136000^b	CLU	8p21.1	CG [54]

This table summarizes the most promising single SNPs relevant to AD research and identified from associations with neuroimaging characteristics. These characteristics show correlations with the SNP alleles either specifically in AD-related regions (in healthy adults) or anywhere in the brain (in normal adults and those with AD and/or MCI).
Key: GM: gray matter; WM: white matter; MTL: medial temporal lobe; PHG: parahippocampal gyrus; ERC: entorhinal cortex; CG: candidate gene approach; GWA: genome-wide association scan approach; vGWA: voxelwise genome-wide association scan approach.
^aWhite matter lesion volume is calculated from a structural MRI scan (usually a T2-weighted scan), while white matter integrity is measured using diffusion tensor imaging and reflects water diffusion directionality.
^bPreviously identified as an AD risk allele [9].
^cLocations were determined using http://genome.ucsc.edu/ [133], using values from dbSNP build 131.