DNA methylation of imprint control regions associated with Alzheimer’s disease in non-Hispanic Blacks and non-Hispanic Whites

Cevik, Sebnem E.; Skaar, David A.; Jima, Dereje D.; Liu, Andy J.; Østbye, Truls; Whitson, Heather E.; Jirtle, Randy L.; Hoyo, Cathrine; Planchart, Antonio

doi:10.1186/s13148-024-01672-4

Table 1 AD-associated DMRs overlapping with candidate ICRs

From: DNA methylation of imprint control regions associated with Alzheimer’s disease in non-Hispanic Blacks and non-Hispanic Whites

Number	ICR	ICR coordinates	DMR coordinates	Nearest transcript	Distance to closest gene (bp)	Race/ethnicity	%Parental methylation
1	ICR_17^	chr1:8117511–8117827	chr1:8117067–8117532	RPL7AP18	59,024	NHB	P
2	ICR_20^ (A)	chr1:10682902–10683413	chr1: 10682586– 10683160	CASZ1	0	NHB	P
2	ICR_20^ (B)	chr1:10682902–10683413	chr1: 10682972– 10683160	CASZ1	0	ALL	P
3	ICR_39	chr1:38210131–38210429	chr1:38210102–38210802	LINC01343	0	NHB	P
4	ICR_54	chr1:112742974–112743310	chr1:112743018–112743108	NUTF2P4	4785	NHB	M**
5	ICR_55^ (A)	chr1:116641652–116642769	chr1:116642521–116642780	IGSF3	0	NHB
5	ICR_55^ (B)	chr1:116641652–116642769	chr1: 116642465–116642749	IGSF3	0	ALL
6	ICR_67^&	chr1:161442725–161442826	chr1:161442654–161442757	FCGR2A	62,604	NHB
7	ICR_78^ (A)	chr1:203076164–203076460	chr1:203076065–203076495	PPFIA4	0	NHB
7	ICR_78^ (B)	chr1:203076164–203076460	chr1: 203076065 –203076234	PPFIA4	0	ALL
8	ICR_88	chr1:228619143–228619258	chr1:228619100–228619407	RNA5S5	0	NHB
9	ICR_89^^&	chr1:228620967–228621017	chr1:228620811–228621043	RNA5S6	428	NHW
10	ICR_92^	chr1:228632865–228633148	chr1:228632864–228633210	RNA5S11	116	NHB
11	ICR_93^^&	chr1:228635189–228635657	chr1:228635411–228635654	RNA5S12	200	NHW
12	ICR_94	chr1:228636250–228636431	chr1:228636252–228636353	RNA5S13	663	NHW
13	ICR_106^	chr1:244729465–244729883	chr1:244729523–244729966	DESI2	20,432	NHB
14	ICR_116^	chr2:28342638–28342806	chr2:28342650–28342769	BABAM2	3737	NHB	P
15	ICR_125 (A)	chr2:54289850–54290281	chr2: 54289947 –54290188	ACYP2	0	NHB	M
15	ICR_125 (B)	chr2:54289850–54290281	chr2: 54289947– 54290255	ACYP2	0	ALL	M
16	ICR_137^&	chr2:105236991–105237239	chr2:105237149–105237194	GPR45	4504	ALL	M**
17	ICR_140^^&	chr2:112433099–112433213	chr2:112433150–112433260	RGPD8	0	NHW
18	ICR_144	chr2:120526146–120526533	chr2:120525904–120526415	LINC01101	59,797	NHB	P
19	ICR_163*^ (A)	chr2:181574336–181575348	chr2: 181574501 –181574918	CERKL	0	NHB
19	ICR_163*^ (B)	chr2:181574336–181575348	chr2: 181575328– 181575420	CERKL	0	NHB
20	ICR_180^	chr2:230991059–230991241	chr2:230991094–230991158	SPATA3	4883	NHB
21	ICR_188	chr2:241902453–241902725	chr2:241902629–241902778	LINC01237	0	NHB	M
22	ICR_203*^	chr3:46558604–46558922	chr3:46558570–46558679	LRRC2	0	ALL	M**
23	ICR_207	chr3:50481168–50481455	chr3:50481297–50481636	CACNA2D2	0	NHB	P
24	ICR_211 (A)	chr3:96776774–96777017	chr3:96776899–96777065	CDV3P1	0	NHB
24	ICR_211 (B)	chr3:96776774–96777017	chr3:96776927– 96777065	CDV3P1	0	ALL
25	ICR_238*^^&	chr4:1050914–1051080	chr4:1050995–1051010	RNF212	5168	ALL
26	ICR_244	chr4:3702565–3703061	chr4:3703028–3703124	LINC02171	24,710	ALL	P
27	ICR_268	chr4:55158026–55158180	chr4:55158025–55158163	KDR	32,431	NHB
28	ICR_273^	chr4:81153935–81154202	chr4:81153919–81154077	PRKG2	0	NHW
29	ICR_281	chr4:152009424–152009915	chr4:152009643–152010206	RNA5SP169	37,811	ALL	P
30	*ICR_287^ (A)**	chr4:184097251–184097401	chr4:184097176–184097474	ENPP6	0	NHB	M**
30	ICR_287*^ (B)	chr4:184097251–184097401	chr4: 184097286 –184097326	ENPP6	0	ALL	M**
31	ICR_315	chr5:55178062–55178152	chr5:55177765–55178063	CDC20B	4885	NHB	M**
32	ICR_324	chr5:110894251–110894443	chr5:110894333–110894361	BCLAF1P1	51,830	NHB	M
33	ICR_326*^	chr5:136079156–136079563	chr5:136079562–136079640	TGFBI	15,338	NHB	M
34	ICR_327^ (A)	chr5:136079902–136080957	chr5:136080178–136081178	TGFBI	16,084	NHB	M**
34	ICR_327^ (B)	chr5:136079902–136080957	chr5: 136080656– 136080693	TGFBI	16,084	ALL	M**
35	ICR_352	chr5:171319025–171319892	chr5:171318815–171319422	TLX3	6886	NHB	P
36	ICR_367^ (A)	chr6:10099407–10099822	chr6:10098961–10099504	OFCC1	0	NHB
36	ICR_367^ (B)	chr6:10099407–10099822	chr6:10099389– 10099472	OFCC1	0	ALL
37	ICR_423*^	chr6:170423032–170423404	chr6:170423063–170423130	FAM120B	15,284	NHB
38	*ICR_434^ (A)**	chr7:2019844–2020175	chr7:2019610–2020099	MAD1L1	0	NHB
38	ICR_434*^ (B)	chr7:2019844–2020175	chr7: 2019100– 2019845	MAD1L1	0	ALL
39	ICR_439*^	chr7:5144439–5144757	chr7:5144438–5144493	ZNF890P	0	NHB	M
40	ICR_452^	chr7:45564015–45564354	chr7:45563920–45564036	ADCY1	9786	NHB	P
41	ICR_470^	chr7:73330191–73330782	chr7:73330658–73331092	FKBP6	0	NHB
42	ICR_473^	chr7:76150206–76150703	chr7:76149513–76150704	GTF2IP7	41,444	NHB
43	ICR_481*^# (A)	chr7:130490640–130494200	chr7: 130494195– 130494648	MEST\|MESTIT1	0	NHB	M
	*ICR_481^# (B)**	chr7:130490640–130494200	chr7: 130492063– 130492131	MEST\|MESTIT1	0	NHW	M
	ICR_481*^# (C)	chr7:130490640–130494200	chr7: 130492246– 130492270	MEST\|MESTIT1	0	ALL	M
	ICR_481*^# (D)	chr7:130490640–130494200	chr7: 130494195– 130494648	MEST\|MESTIT1	0	ALL	M
44	ICR_484^	chr7:138664218–138664771	chr7:138664233–138664251	SVOPL	0	NHB
45	ICR_491	chr7:155071148–155071376	chr7:155071182–155071231	HTR5A	0	NHB	M
46	ICR_533 (A)	chr8:57280020–57280373	chr8:57280257–57280374	LINC00588	0	NHB	P**
46	ICR_533 (B)	chr8:57280020–57280373	chr8:57280257– 57280350	LINC00588	0	ALL	P**
47	ICR_545	chr8:110202766–110202966	chr8:110202860–110202920	RPSAP48	96,802	NHW
48	ICR_548*^#	chr8:140098048–140100981	chr8:140098530–140098591	TRAPPC9\|PEG13	0	NHB	M
49	ICR_568	chr9:40584494–40584535	chr9:40584526–40584688	AQP7P5	85,470	NHW
50	ICR_597	chr9:67720383–67720553	chr9:67720318–67720505	FAM27E3	1204	NHB
51	ICR_600	chr9:87944657–87944766	chr9:87944482–87944658	SPATA31C1	21,000	NHB	M
52	ICR_602	chr9:89859835–89860135	chr9:89860037–89860136	UNQ6494	140,076	ALL	P**
53	ICR_605 (A)	chr9:105519837–105519944	chr9:105519843–105519880	FSD1L\|RALGAPA1P1	0	NHW	M**
53	ICR_605 (B)	chr9:105519837–105519944	chr9:105519846– 105519890	FSD1L\|RALGAPA1P1	0	ALL	M**
54	ICR_607^	chr9:110172756–110173053	chr9:110172902–110172965	PALM2-AKAP2	244	NHB\|ALL
55	ICR_615^	chr9:127897741–127897833	chr9:127897740–127898133	ST6GALNAC6	0	NHB
56	ICR_621^	chr9:134800924–134801207	chr9:134800923–134801007	COL5A1	0	NHB
57	ICR_633^	chr10:5645451–5645631	chr10:5645450–5645555	ASB13	0	NHB\|ALL	P
58	ICR_644^	chr10:28326170–28327001	chr10:28326690–28326841	ZNF101P1	12,276	NHB	P
59	ICR_659	chr10:61867420–61867672	chr10:61867650–61867680	LINC02625	0	NHB	M**
60	ICR_664^	chr10:71266448–71266685	chr10:71266523–71267095	UNC5B	0	NHB	P
61	ICR_684	chr10:125773898–125774247	chr10:125774034–125774127	MMP21	0	NHW
62	ICR_710^^&	chr11:400577–400771	chr11:400612–400787	PKP3	0	ALL
63	ICR_716*^#	chr11:1997886–1999417	chr11:1998628–1998714	MRPL23\|H19	0	NHB	P
64	ICR_719*^#	chr11:2001655–2003118	chr11:2002634–2002682	MRPL23	0	NHW\|ALL	P
65	ICR_744*^	chr11:96341424–96341836	chr11:96341176–96341443	MAML2\|MIR1260B	0	NHB
66	ICR_794^	chr12:110247427–110248050	chr12:110247783–110248328	IFT81	28,634	NHB
67	ICR_805^	chr12:130686671–130687021	chr12:130685426–130687022	RIMBP2	0	NHB
68	ICR_808	chr12:132514078–132514147	chr12:132513962–132514680	FBRSL1	0	NHB	P**
69	ICR_814^&	chr13:20142811–20142911	chr13:20142817–20142897	GJA3	0	NHB	M
70	ICR_827*^	chr13:60267612–60268519	chr13:60267683–60267898	LINC00434	0	ALL	M
71	ICR_829^	chr13:80654682–80655272	chr13:80654681–80654939	PWWP2AP1	125	NHB	M
72	ICR_831^	chr13:100521893–100522472	chr13:100522193–100522667	PCCA	0	NHB
73	ICR_832^ (A)	chr13:106490937–106491301	chr13:106491112–106491204	EFNB2	0	NHB
73	ICR_832^ (B)	chr13:106490937–106491301	chr13:106491112–106491536	EFNB2	0	ALL
74	ICR_839*	chr13:113802775–113802965	chr13:113802908–113802957	TMEM255B	0	NHB
75	ICR_843*	chr13:114199984–114200221	chr13:114200003–114200127	CFAP97D2	0	NHW	M**
76	ICR_873*^#	chr14:100824556–100828242	chr14:100827448–100827505	MEG3	0	ALL
77	ICR_893*^^&	chr15:24954592–24956828	chr15:24955432–24955502	SNHG1\|SNRPN\|SNURF	0	NHB	M
78	ICR_902^^& (A)	chr15:56007034–56007264	chr15:56006890–56007288	CNOT6LP1	0	NHB
78	ICR_902^^& (B)	chr15:56007034–56007264	chr15:56007215– 56007288	CNOT6LP1	0	ALL
79	ICR_914^	chr15:99476322–99476786	chr15:99476061–99476586	LINC02244	73,869	NHB	P
80	ICR_918 (A)	chr16:561123–561328	chr16:561079–563336	PRR35	0	NHB
80	ICR_918 (B)	chr16:561123–561328	chr16: 561079– 561329	PRR35	0	ALL
81	ICR_922^	chr16:2038931–2039033	chr16:2038752–2038952	SLC9A3R2	0	ALL	P**
82	*ICR_927^ (A)**	chr16:3443280–3444094	chr16:3443244–3443387	ZNF597\|NAA60	0	NHW
82	*ICR_927^ (B)**	chr16:3443280–3444094	chr16: 3443128– 3443337	ZNF597\|NAA60	0	ALL
83	ICR_935	chr16:31428164–31428239	chr16:31428174–31428193	COX6A2	0	NHB	M**
84	*ICR_966^**	chr16:67654637–67654865	chr16:67654392–67654671	CARMIL2	0	NHB
85	ICR_976^	chr16:87517952–87518116	chr16:87517903–87519115	ZCCHC14	24,928	NHB	P**
86	ICR_978 (A)	chr16:88431177–88431330	chr16:88431219–88433792	ZNF469	0	NHB
86	ICR_978 (B)	chr16:88431177–88431330	chr16:88431219– 88432676	ZNF469	0	ALL
87	ICR_979^	chr17:335949–336142	chr17:335938–335966	RPH3AL	0	NHB\|ALL	P**
88	ICR_987^& (A)	chr17:5771207–5771575	chr17:5771278–5771364	NLRP1	186,698	NHB	M**
	ICR_987& (B)	chr17:5771207–5771575	chr17:5771284– 5771340	NLRP1	186,698	NHW	M**
	ICR_987& (C)	chr17:5771207–5771575	chr17:5771252– 5771364	NLRP1	186,698	ALL	M**
89	ICR_1027 (A)	chr17:79517963–79518428	chr17:79517720– 79517977	RBFOX3	0	NHB	P
	ICR_1027 (B)	chr17:79517963–79518428	chr17:79518326– 79518634	RBFOX3	0	NHB	P
	ICR_1027 (C)	chr17:79517963–79518428	chr17:79517916–79517973	RBFOX3	0	ALL	P
90	ICR_1045*^ (A)	chr18:79404293–79404545	chr18:79404213-79404841	NFATC1	0	NHB	P**
90	ICR_1045*^ (B)	chr18:79404293–79404545	chr18:79404222 –79404294	NFATC1	0	ALL	P**
91	ICR_1046	chr18:79532208–79532443	chr18:79532261–79532411	NFATC1	2885	NHB
92	ICR_1071^	chr19:3375239–3375520	chr19:3374971–3375300	NFIC	0	NHB
93	ICR_1079	chr19:6509209–6509630	chr19:6509440–6509508	TUBB4A	6361	NHB	P
94	ICR_1103^^&	chr19:21568786–21569830	chr19:21569406–21569812	ZNF429	27,629	NHW
95	ICR_1104*^&	chr19:21678108–21678334	chr19:21678184–21678290	MTDHP3	0	ALL
96	ICR_1108^	chr19:30253854–30254259	chr19:30253405–30253912	ZNF536	0	NHB
97	ICR_1139^(A)	chr19:55493632–55493692	chr19:55493661–55493693	SSC5D	0	NHB
97	ICR_1139^(B)	chr19:55493632–55493692	chr19: 55493661– 55493706	SSC5D	0	ALL
98	*ICR_1142^#**	chr19:56837320–56841439	chr19:56839300–56839440	ZIM2\|PEG3\|MIMT1	0	ALL	M
99	ICR_1187^&	chr20:30892127–30892735	chr20:30892682–30892758	DUX4L38	1726	NHB
100	ICR_1191*^	chr20:31547027–31548129	chr20:31547408–31547421	HM13\|MCTS2P	0	ALL	M
101	ICR_1192^# (A)	chr20:37520202–37521842	chr20: 37520201– 37520271	BLCAP\|NNAT	0	NHB	M
101	ICR_1192^# (B)	chr20:37520202–37521842	chr20: 37520954 –37521054	BLCAP\|NNAT	0	NHB	M
102	*ICR_1206^#**	chr20:58850158–58852357	chr20:58851318–58851371	GNAS	0	NHB	M
103	ICR_1207*^ (A)	chr20:58853850–58856828	chr20: 58855056– 58855067	GNAS	0	NHB	M
103	*ICR_1207^ (B)**	chr20:58853850–58856828	chr20: 58854476– 58854553	GNAS	0	ALL	M
104	ICR_1208^	chr20:58888275–58890270	chr20:58890064–58890121	GNAS	0	NHW
105	ICR_1217*	chr20:63482662–63482947	chr20:63482840–63483019	EEF1A2	5067	NHB
106	ICR_1236^&	chr21:8214822–8214873	chr21:8214757–8214857	RNA45SN2\|RNA28SN2	0	NHW
107	ICR_1241	chr21:8220792–8221021	chr21:8221013–8221077	RNA45SN2	1490	NHW
108	ICR_1242	chr21:8226175–8226554	chr21:8226206–8226311	RNA45SN2	6873	NHW
109	ICR_1244	chr21:8249017–8249144	chr21:8249128–8249371	RNA18SP5	4698	NHW
110	ICR_1254	chr21:8259990–8260098	chr21:8259878–8260036	RNA18SP5	4286	NHW
111	ICR_1266	chr21:8399142–8399444	chr21:8399429–8399518	RNA45SN3\|RNA28SN3	0	NHW
112	ICR_1269	chr21:8409174–8409553	chr21:8409173–8409454	RNA45SN3	6831	NHW
113	ICR_1271	chr21:8432767–8432863	chr21:8432792–8432919	RNA45SN1	359	NHW
114	ICR_1273	chr21:8434286–8434377	chr21:8434255–8434399	RNA45SN1	0	NHW
115	ICR_1275	chr21:8437284–8437586	chr21:8436713–8437584	RNA45SN1\|RNA18SN1	0	NHW
116	ICR_1284	chr21:8453321–8453640	chr21:8453320–8453701	RNA45SN1	6749	NHW
117	ICR_1377*^	chr22:42532792–42533280	chr22:42532982–42533635	RRP7A	12,996	NHB	P
118	ICR_1389^	chr22:50482322–50482580	chr22:50482321–50482623	ADM2	12,996	NHB
119	ICR_1409*^	chrX:39813662–39814142	chrX:39813989–39814100	MIR1587	23,419	NHB	P**
120	ICR_1476^	chrX:153780931–153781167	chrX:153780908–153781001	SRPK3	0	ALL	P**

ICRs when the DMRs between AD cases and controls differed by ≥ 10% (Black) and ≥ 15% (Bold). In this subset of 45 ICRs, identified with a more stringent cutoff (≥ 15%), only one DMR (chr15:26670350-26670605) emerged that is not present with the 10% cutoff
^*ICRs overlapping ENCODE annotated regions of CTCF binding [35]
^ ICRs overlapping ENCODE annotated regions of DNase I hypersensitivity [35]
^#ICRs overlapping previously published ICRs of imprinted genes [35, 55,56,57,58,59,60,61,62,63,64,65,66,67,68]
^&ICRs that overlap previously established regions of systemic interindividual variation (SIVs) [35, 91]
% Parental methylation denotes whether the paternal (P, sperm) or maternal (M, oocyte) allele of an ICR is methylated based upon both sperm and oocyte methylation data [35]
^**Parental allele methylation of an ICR based upon only sperm methylation [35]
ε ICR_716 and ICR_719 overlap with the same known ICR proximity to H19/MRPL23; ICR_1206, ICR_1207 and ICR_1208 overlap with the same known ICR proximity to GNAS

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ISSN: 1868-7083

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