Table 3 Associations between blood pressure or hypertension and epigenome-wide DNA methylation
From: Accelerated epigenetic age in hypertension: a systematic review and meta-analysis
Author, Year | Quality1 | Population | Male (%), Age, sample size, country | Platform | Tissue type | Number of CpGs/DMRs detected | Top gene(s) annotated | Definition of HTN/BP | Associations between epigenome-wide DNA methylation and HTN and/or BP. |
|---|---|---|---|---|---|---|---|---|---|
Bai et al. 2022 [122] | 8/9 | HTN/Pre-HTN | Discovery: 1:1 ratio3, 58.2 (5.1), 132, China Validation: 1:0.8 ratio3, 59.96 (5.5), 203, China | 450 K | PBC | Discovery: 25 CpGs | MBLP, PVT1, CCDC85C, COLEC11, MAML2, PYROXD1, OVGP1, ADAMTS19, MCF2L, PSORS1C1 | HTN: Double-arm SBP and DBP values ≥ 160 mmHg and ≥110 mmHg respectively, or SBP ≥ 140 mmHg and/or DBP ≥ 90 mmHg after receiving anti-HTN treatment. | Discovery: 25 CpG sites with a selection criterion of a DiffScore >13 and ∆β > 0.1 identified though overlap of differentially methylated CpGs between HTN vs healthy controls and between patients with prehypertension who progressed to hypertension vs those who did not progress to hypertension. Validation: by pyrosequencing. |
Boström et al. 2016 [179] | 6/9 | Discovery: Bariatric surgery Validation: ArrayExpress databasesd | Discovery: 63.6, 46.9 (11.9), 11, Switzerland Validation: 50.9, 64.9 (13.2), 540, N/A4 | 450 K | WB | Discovery: 22 CpGs Validation:2 CpGs | MCC1, SKOR2, VGLL3, WSB1, EHMT2, TCF12, MAP2K4, FAM54A, SORBS1, DDX55, ATXN1L, EFEMP1, CRKL, STEAP3, CPEB4, RHOBTB2, ATXN1L, TSSK1B, SPPL2A, BHLHA9, CHCHD5, NRTN | BP: Measured once after overnight fast, in sitting position, after 5 min relaxation, before and six months after surgery. HTN: Yes/No to HTN provided by original cohort study author. | Discovery: Methylation changes at 22 CpGs correlated with SBP six months after RYGB surgery. Validation: 2 CpG sites (SKO2, P = 2.79E-02; EHMT2, P = 2.30E-02) significantly hypomethylated in HTN. |
Caspers et al. 2019 [180] | 5/9 | LLSLFH | 100, 49.0 (11.8), 68, Belgium | 450 K | WB | 5 CpGs | MECOM, CACNB2, CETP, G6PC2, SH2B3 | BP: BP was measured three times in the morning seated. Average (ABP) of SBP and DBP was used. | 5 CpGs associated with ABP or ΔABP promoter region overlapping with genetic variants linked to 1 or more MetS phenotypes. No associations with ABP or ΔABP at FDR P < 0.05. |
Chen et al. 2023 [130] | 7/9 | TWB | 47.9, 49.7 (0.43), 1442, Taiwan | 850 K | WB | 1 CpG | GPNMB | BP: indication of measurement. | HTN patients had ↑ cg17274742 methylation. |
Ciantar et al. 2024 [181] | 6/9 | Discovery: YFS Replication: LURIC | Discovery: 50.6, 43.0 (37.0, 46.0), 969, Finland Replication: 69, 62.8 (10.7), 2371, Germany | 850k | PBC | Discovery: 1 DMR Replication: 1 CpG | Discovery: LDHAL6A Replication: LINC01237 | BP: 3 successive measurements taken on right arm of the participants after 5-min rest while seated. | Discovery: 1 DMR associated with SBP (P = 3.8E-02). Replication: 1 CpG associated with DBP (P < 1.2E-02). |
Cronje et al. 2020 [182] | 7/9 | PURE-SA-NW | 100, 63 (N/A)2, 120, Botswana | 850k | WB | 1 CpG | MED13L | BP: SBP and DBP measured twice in seated or upright position with 5-minute interval. | 2% methylation ↑ in cg03621504 was associated with a 10 mmHg increase in SBP. |
da Silva Rodrigues et al. 2024 [183] | 7/9 | Older women | 0, 60.7 (4.1), 40, Brazil | 850k | PBC | 35 CpGs | Top CpGs: ACE, ABCA7, SORL1, IQCK, | BP: indication of measurement. | 35 CpGs were differentially methylated in response to reduced SBP and DBP (P < 0.05). |
Das et al. 2016 [184] | 7/9 | Discovery: GOLDN Validation: BHS | Discovery: 51.5, 53.52, 846, USA Validation: BHS EU: N/A3, 44.1 (4.1), 603, USA BHS AfriA: N/A3, 43.5 (4.5), 269, USA | 450k | Discovery: CD4 + T cells Validation: WB | Discovery: 2 CpGs Validation: BHS EU: 2 CpGs BHS AfriA: 2 CpGs | CPT1A | BP: BP measured seated after 5 minutes rest. | Discovery: ↓ methylation at cg00574958 associated with meeting MetS BP criteria (HTN) (P < 0.0001). ↓ methylation cg17058475 associated with HTN (P < 0.05). Validation: Both CpGs significantly associated with MetS in both BHS EU and BHS AfriA. |
Fernández-Sanlés et al. 2018 [27] | 7/9 | Discovery: REGICOR Validation: FHS-OS | Discovery: 48.2, 58.5 (9.3), 465, Spain Validation: 46.9, 63.5 (7.3), 1823, USA | 450k | Discovery: PBC Validation: BC | Discovery: N/A Validation: N/A | N/A | BP: SBP and DBP measured twice with lower value recorded. | Discovery, Validation and Meta-analysis: No association with SBP or DBP in either cohort or in the overall meta-analysis at P < 7.81E-04. |
Hong et al. 2023 [28] | 7/9 | CNTR | Cross sectional: 68.7, 49.9 (12.2), 1072, China Longitudinal Baseline: 60.7, 50.2 (10.2), 308, China Follow up: 60.7, 54.9 (10.2), 308, China | 450 K 850 K | PBC | Cross sectional: 33 CpGs Longitudinal: 9 CpGs | Cross sectional: GALE, SLC1A5, STAB1, EGFL7, ANKRD34B, LOC100132354, CPT1A, LMNA, SCNN1A, CDC42BPB, DNMT3B, ADAM8, LRRC33, VPS37B, TSPAN2, MKLN1, TXNIP, CDK6, SLC7A11, SLC43A1, SLC9A3R1, RAB7A, FAM117A, B3GALT4, FAM60A, PHGDH, ZDHHC18 Longitudinal: CPT1A, ANKRD34B, DNMT3B, MKLN1, SLC4341, LMNA | BP: BP measured twice on right arm in sitting position after 5 min of rest with the average calculated. If measurements differed by >10 mmHg another measurement was taken. HTN: SBP ≥ 140 mmHg and/or DBP ≥ 90 mmHg and/or antihypertensive medication usage. | Cross sectional: 7 previously reported CpGs significantly associated with SBP and 3 CpGs significantly associated with DBP in total cohort. Discordant MZ twin analysis outlined 11 CpGs associated with SBP and 18 CpGs associated with DBP. Longitudinal: 2 CpGs significant comparing baseline DNA methylation to follow-up SBP. 3 CpGs significant comparing baseline SBP to follow-up DNA methylation. 3 CpGs significant comparing baseline DNA methylation to follow-up DBP. 1 CpG significant comparing baseline DBP to follow-up DNA methylation. |
Huan et al. 2019 [185] | 7/9 | FHS-OS FHS-TG | FHS-OS: 46, 66.4 (8.9), 2648, USA FHS-TG: 48, 45.4 (7.8), 1522, USA | 450 K | BC | 14 CpGs | CNNM2, SIPA1, FAM109A, LASS5, SOX7, OR4B1, HIVEP3, CLN8, SDCCAG8, PHACTR1, PRSS42, TSHZ3, MACROD1, HSPB7, TRAPPC9, SPINK8, SEMA7A, PLAC9, CLN8, IRF1, KCNH2, SCAMP2, FLII, NME6 | BP: BP measured twice by a physician; average taken. | Mendelian randomisation analysis identified 37 causal CpGs for BP. 29 CpGs associated with SBP and 22 CpGs associated with DBP. |
Kato et al. 2015 [186] | 8/9 | Discovery: LOLIPOP IA Validation: LOLIPOP IA 2 LOLIPOP EU LifeLines DEEP RS-BIOS KORA | Discovery: LOLIPOP1A: 74.2, 51.9 (10.2), 1904, UK (S.Asian) Validation: LOLIPOP1A 2: 47.0, 51.8 (10.2), 1373, UK (S. Asian) LOLIPOPEU: 50.6, 55.6 (9.5), 166, UK LifelinesDeep: 42.3, 45.5 (13.3), 752, Netherlands RS-BIOS: 42.5, 67.7 (5.9), 762, Netherlands KORA: 48.9, 61.0 (8.9), 1727, Germany | 450 K | LOLIPOP: WB LifelinesDeep: WB RS-BIOS: WB KORA: WB | Discovery: 28 CpGs | CASZ1, MTHFR, OSR1, KCNK3, ULK4, PRDM8, ARHGAP24, NPR3, PRDM6, ABLIM3, EBF1, TTBK1, PLEKHG1, IGFBP3, TBC1D12, TRIM8, ADRB1, SYT7, ARHGAP42, ADAMTS8, GALNT4, FAM109A, RPP25, FES, DCAKD, HOXB3, TBX2, AMH | HTN: SBP ≥ 160 mmHg and/or DBP ≥ 100 mmHg and/or antihypertensive usage. BP: measured to standardised protocols. | Discovery: 28/35 sentinel blood pressure SNPs associated with one or more CpGs at P < 3.8E-06. 10 CpGs associated with MAP, 6 CpGs associated with PP, 9 CpGs associated with SBP and 3 CpGs associated with DBP. Validation: All 28 CpGs replicated in further testing with consistent direction of effect. |
Kazmi et al. 2020 [187] | 7/9 | SABRE | Trans-ancestry: 100, 51 (7.1), 712, UK EU: 100, 52 (7.2), 364, UK S.Asian: 100, 51 (7.0), 348, UK | 450 K | PBC | Trans-ancestry: 9 CpGs 620 DMRs EU: 3 CpGs 435 DMRs S.Asian: 1 CpGs 247 DMRs | Trans-ancestry CpGs: FHL2, MYO5C, ELOVL2, KLF14, AHRR, MYO1G, OR8U8;OR5AP2, PPP1R2, LOC100132354 Top 5 DMRs SBP trans-ancestry: CUX1, LOC729156, ARHGAP12, C21orf129, NCRNA00112 Top 5 DMRs DBP trans-ancestry: DDX10, UNKL, CD44, GNG7, DRNA5, EU CpGs: CEBPD, AHRR, C12orf44, AFAP1-AS1, Top 5 DMRs SBP EU: CUX1, LOC729156, ARHGAP12, C21orf129, SR140, CAMTA1, NDE1, ATP10D, IRF8, FJ39582 Top DMRs SBP EU: BBS1, BCORL1, NCKAP5, DYNC1I1, MYLK, ACSL4, BANP, PRDM2, DNAJC8, SLC4A11 S.Asian GALR2, Top DMRs SBP S.Asian: C17orf53, MTCH1, CRTAM, ELL2, BCOR, C3orf21, FAM194A, MSRA, TRPM1, ALDH15A1 Top DMRs DBP S.Asian: ELL2, ALDH16A1, PID1, DDX10, CD44, ZNF77, ADAMTS5, MSRB3, FXN, SNORD113-7 | HTN: SBP ≥ 140 mmHg and/or DBP ≥ 90 mmHg and/or antihypertensive medication usage. BP: BP measured twice in sitting position after participant had urinated and rested for 5 minutes. | Trans-ancestry: 4 CpGs associated with SBP (P < 1.24E-07). After adjustment for cofounders no longer significant. 2 CpGs associated with DBP (P < 1.24E-07). After adjustment 1 additional CpG was identified. 2 CpGs associated with HTN (P < 1.24E-07). After adjustment these associations no longer remains significant. 395 DMRs (mapped to 326 genes) were associated with SBP. 237 DMRs (mapped to 157 genes) were associated with DBP FDR (P < 0.05). EU: 3 CpGs were associated with DBP (P < 1.24E-07). When adjusted 2 of these CpGs remained significant with consistent direction of effect. 1 additional CpG was identified. 348 DMRs (mapped to 291 genes) associated with SBP. 95 DMRs (mapped to 74 genes) associated with DBP FDR (P < 0.05). S.Asian: 1 CpGs associated with SBP (P < 1.24E-07). After adjustment not significant. 96 DMRs (mapped to 66 genes) associated with SBP. 186 DMRs (mapped to 135 genes) were associated with DBP FDR (P < 0.05). |
Kho et al. 2020 [92] | 6/9 | GENOA | 28.6, 63.6 (9.2), 1218, USA | 450 K 850 K | PBC | 3 CpGs | LOC100132354, CPT1A, TXNIP | BP: BP was measured twice in sitting position for 5 minutes, average taken. HTN: SBP ≥ 140 mmHg and/or DBP ≥ 90 and/or antihypertensive medication usage. | 3 previously reported CpGs associated with BP (P < 0.0038). 2 CpGs associated with SBP while 1 CpG associated with DBP (P = 0.0006). |
Kidambi et al. 2021 [188] | 6/9 | Post-menopausal women and men with HTN | N/A3, 51 (9), 50, USA | RBBS | T-Cells, Frozen arterioles | T Cells: 1 DMR Arterioles: 3 DMRs | T Cells: Chr12:34499685-34499731 Arterioles: MESTIT1, MEST, NXPH4, chr17:26578249-26578315 | BP: BP measured three times 1 minute apart with the subject seated with after 5 minutes rest. HTN: SBP ≥ 130 mmHg and/or DBP ≥ 80 mmHg and/or antihypertensive medication usage. | T Cells: Changes in DBP (due to sodium restriction) were associated with one intergenic DMR (Padj=0.01). Arterioles: Changes in SBP associated with 1 DMR (MESTIT1:MEST, Padj = 0.0067). Changes in DBP associated with 1 intergenic DMR (Padj=0.044). One DMR associated with change in DBP however did not remain significant after adjustment (Padj=0.075). |
Kucher et al. 2017 [189] | 4/9 | CAH and AHTN | 100, 55.5 (6.5), 6, Russia | 27 K | WBC, CAAP | WBC: 3 CpGs CAAP: 3 CpGs | WBC: MIR615, MIR7-3 CAAP: MIR10B, MIR675 | HTN: Medical history | WBC: Duration of HTN associated with 3 CpGs (P < 0.05). CAAP: Duration of HTN associated with 3 CpGs (P < 0.05). |
Lee et al. 2024 [190] | 7/9 | KARE HEXA | KARE: 52.9, 58 (47, 78), 1,526, S. Korea HEXA: 75.5, 52 (40, 60), 808, S. Korea | 850 K | WB | KARE: 2 CpGs HEXA: 2 CpGs Overall Meta-analysis: 4 DMRs for both SBP and DBP | KARE: CPT1A, SLC13A5 HEXA: CPT1A, SLC13A5 Overall Meta-analysis: SLC25A29, SLC16A11, ZNF835, CAST, CPT1A, ACSF3 | BP: indication of measurement HTN: SBP ≥ 130 mmHg and/or DBP ≥ 80 mmHg and/or antihypertensive medication usage | KARE: 2 CpGs associated with SBP (P < 4.41E-06). HEXA: 2 CpGs associated with SBP (P < 2.96E-03). Overall Meta-analysis: 4 DMRs associated with SBP (P < 1.49E-07). 4 DMRs associated with DBP (P < 2.49E-09). |
Lim et al. 2017 [191] | 7/9 | Elderly Gen Pop | Discovery: 6.0, 73.3 (4.1), 50, South Korea Validation: 9.6, 72.3 (3.8), 52, South Korea | 450 K | WB | 2 CpGs | ZKSCAN4, ZNF227 | BP: measured twice in sedentary position after 10 minutes rest with a 10 minute interval between measurements and average taken. HTN: self-reported medication information. | Discovery and validation combined: 10% ↑ in mean methylation of 2 CpGs was associated with a 4.0 mmHg increase in DBP. 10% ↑ in methylation of cg21194911 was associated with a 2.7 mmHg increase in DBP. 10% ↑ in methylation of cg21761427 was associated with 5.0 mmHg increase in DBP. |
Lin et al. 2016 [192] | 6/9 | LBC1921 LBC1936 | LBC1921: 40, 79.1 (0.6), 446, Scotland LBC1936: 51, 69.5 (0.8), 920, Scotland | 450 K | WB | 1 CpGs | CLCN6 | BP: indication of measurement | CLCN6 was correlated with SBP (r = -0.022) and DBP (r = 0.013). |
Lu et al. 2020 [193] | 7/9 | LifelinesDEEP | 42, 46 (36-55)2, 622, Netherlands | 450 K | WB | 4 CpGs | MIR1249, SLC6A19, IL12RB2 | BP: 10 measurements over 10 minutes. | 1 CpG associated with SBP and 3 CpGs associated with DBP (FDR < 5%). |
Mens et al. 2020 [194] | 7/9 | RS-II-3 RS-III-2 RS-III-1 | RS-II-3 + RS-III-2: 42.4, 67.5 (5.9), 717, Netherlands RS-III-1: 45.8, 59.8 (8.16), 721, Netherlands | 450 K | PBC | 109 CpGs | MIR196A23B, MIR6773, MIR3941, MIR125B5P, MIR19085P, MIR4729, MIR6766, MIR489, MIR653, MIR4721 | BP: measured twice while sitting separated by count of pulse rate with average taken. | 50 CpGs associated with SBP. 59 CpGs were associated with DBP in miRNAs identified via GWAS (P < 0.05). |
Mo et al. 2020 [161] | 8/9 | MQTL: BSGS LBC CC: CATIS SMSS | MR: BSGS: 614 LBC: 1,366 IS Cohort: 53.4, 61.0 (11.87), 2476, China HTN sub-cohort: 52.0, 66.1 (11.87), 1269, China | 450 K | MQTL: BSGS: WB LBC: PBC CC: WBC | 510 CpGs | SBP: CNNM2, NT5C2, SLC5A11, FES, TNRC6A, CASZ1, TNXB, FAM109A, ADAMTS8, HOXA13 DBP: FAM109A, NOV, CPEB4, ZSCAN12L1, ZN389, CNNM2, ZSCAN16, SH2B3, CYP21A2, FES | BP: Three consecutive BP measures taken after 30 minutes rest with average taken. HTN: SBP ≥ 140 mmHg and/or DBP ≥ 90 mmHg and/or antihypertensive usage | MR: 173 CpGs in 90 genes associated with SBP. 337 CpGs in 142 genes associated with DBP (PSMR < 5.67E-07). IS cohort and HTN sub-cohort: Validated through Next-Gen Seq. |
Nuotio et al. 2020 [93] | 7/9 | Discovery: DILGOM (FINRISK) Validation: NFBC1966 | Discovery: DILGOM: 46.2, 51.9 (13.8), 517, Finland Validation: NFBC1966: 45.1, 31.0 (0.3), 670, Finland | 450 K | Discovery: WBC Validation: WBC | 16 CpGs | Discovery: NUMB, GPS1, MYH14, FNDC3B, DOK2, GLIS3, FNDC2B, NBPF8, NBPF12, TXNIP, KCNK17 Validation: ABCG1 | Discovery: BP: measured 3 times after seated at rest for 5 minutes with average of 2nd and 3rd measurement taken. Validation: BP: measured after 15-minute rest period. | Discovery: 7 CpGs associated with SBP. 8 CpG sites associated with DBP (P < 7.33E-06). Validation: 1 CpG associated with DBP which was not observed in the discovery analysis. |
Pan et al. 2024 [195] | 6/9 | HTN | 50.2, 44 (7), 281, USA | RBBS | WB | 24 h-SBP: 108 DMR 24 hr DBP: 119 DMR 24 h-MAP: 104 DMR | Top DMR 24 h-SBP: MMP23B:MMP23A, FAAP20, LDLRAD2:HSPG2 Top DMR 24 h-DBP: CASZ1, MMP23B:MMP23A, PLXNA2 Top DMR 24 h-MAP: MMP23B:MMP23A, PLXNA2 | Clinical BP: measured 4 times every 2 minutes after 10 minute rest. 24 h-BP: BP was measured over a 24 hr period every 20 minutes (AM) or every 45 minutes (PM). | 108 DMR associated with 24 h-SBP, 119 DMR associated with 24 h-DBP and 104 associated with 24 h-MAP (FDR < 0.05). |
Portilla-Fernandez et al. 2019 [196] | 7/9 | RS | 24, 60.6 (5.3), 1450, Netherlands | 450 K | PBC | 3 CpGs | ATG4B, ULK1 | BP: measured twice while sitting separated by count of pulse rate with average taken. | 3 CpGs associated with SBP and 1 CpG associated with DBP (P < 5.63E-05). |
Ramos-Lopez et al. 2018 [197] | 6/9 | MENA | 36.1, 47.2 (14.1), 474, Spain | 450 K | WBC | 4 CpGs | PPKAG2, BHLHE40, PER3, RORA | BP: indication of measurement. | Negative correlation between 4 CpG sites and MAP (P < 0.05). |
Richard et al. 2017 [84] | 8/9 | Discovery: ARIC, CHS, FHS, GENOA, GOLDN, LBC1936, NAS, RS-III, TwinsUK Validation: Amish, ARIC MESA RS-III SYS adults WHI-BAA23 WHI-EPMC | Discovery: ARIC: NA3, 56.6 (5.9), 2743, USA CHS (AA): NA3, 73.0 (5.4), 196, USA CHS (EA): NA3, 76.0 (5.1), 189, USA FHS: NA3, 66.4 (8.9), 2645, USA GENOA: NA3, 60.1 (8.4), 239, USA GOLDN: NA3, 48.8 (15.9), 822, USA LBC1936: NA3, 69.5 (0.8), 903, Scotland NAS: NA3, 72.5 (6.8), 674, USA RS-III: NA3, 59.7 (8.2), 727, Netherlands TwinsUK: NA3, 58.4 (9.3), 690, UK Validation: AMISH: NA3, 46.3 (13.6), 192, USA MESA (AA): NA3, 60.6 (9.2), 236, USA MESA (EA): NA3, 60.8 (9.6), 566, USA MESA (HL): NA3, 59.0 (9.5), 381, USA RS-III: NA3, 67.5 (6.0), 711, Netherlands SYS adults: NA3, 47.2 (4.9), 111, Canada WHI-BAA23 (AA): NA3, 62.8 (6.7), 666, USA WHI-BAA23 (EA): NA3, 68.4 (6.2), 965, USA WHI-BAA23 (HL): NA3, 62.3 (6.8), 333, USA WHI-EMPC (AA): NA3, 62.8 (7.0), 556, USA WHI-EMPC (EA): NA3, 64.7 (7.1), 1092, USA WHI-EMPC (HL): NA3, 61.6 (6.2), 315, USA | 450 K | All (excluding GOLDN): WB GOLDN: CD4 + T Cells | Discovery: 31 CpGs Validation: 13 CpGs Overall Meta-analysis (Discovery + Validation): 126 CpGs | Discovery: SKI, PHGDH, SLC7A11, TXNIP, SLC1A5, CNP, GALE, ZMIZ1, LOC100132354, CPT1A Validation: TSPAN2, PHGDH, TXNIP, SLC7A11, LOC132354, ZMIZ1, CPT1A, SLC1A5 Overall Meta-analysis (Discovery + Validation): PHGDH, SLC7A11, TXNIP, SLC1A5, LOC100132354, SLC43A1, SARS, GARS, CPT1A, CSAD | BP: measured in a sitting position after a period of rest and an average of sequential readings was taken. | Discovery: 31 CpG sites associated with both SBP and DBP (P < 1.0E-07). Validation: 13 of the 31 identified CpG sites associated with SBP and DBP (P < 0.0016). Overall Meta-analysis (Discovery + Validation): 126 CpG sites associated with SBP and DBP (P < 1.0E-07). |
Roberts et al. 2022 [164] | 6/9 | HTN | Discovery: 50.2, 44 (7), 281, USA Validation: 53.8, 42 (7), 117, USA | RBBS | WB | 24 h-SBP: 72 DMRs SBP day: 38 DMRs SBP night: 20 DMRs 24 h-DBP: 12 DMRs DBP day: 9 DMRs DBP night: 4 DMRs 24 h-PP: 22 DMRs PP day: 28 DMRs PP night: 2 DMRs 24 h-MAP: 34 DMRs MAP day: 7 DMRs MAP night: 5 DMRs | Top DMRs 24 hr SBP: PRDM16, COLGALT1, ZC3H4, CFAP100, CASZ1 Top DMRs SBP day: PRDM16, CASZ1, CASKIN1, COLGALT1, ZC3H4 Top DMRs SBP night: OLFM2, ZC3H4, BAIAP3, CASZ1, FAM181B Top DMRs 24 hr DBP: ZC3H4, COLGALT1, CASZ1, FGF19, PRDM16 DBP day: CASZ1, ZC3H4, COLGALT1, PRDM16, FGF19 Top DMRs DBP night: ZC3H4, FGF19, CASZ1 Top DMRs 24 h PP: ALX4, PRR35, CASKIN1, CFAP100, PMPCA Top DMRs PP day: CASKIN1, PMPCA, PRDM16, ALX4, CFAP100, Top DMRs PP night: ALX4 Top DMRs 24 h MAP: PRDMB1491, B152516, PRDM16, COLGALT1, ZC3H4 Top DMRs MAP day: PRDM16, CASZ1, COLGALT1, CFAP100, MPRIP Top DMRs MAP night: ZC3H4, CASZ1, FGF19 | Clinical BP: measured 4 times every 2 minutes after 10 minute rest. 24 h-BP: BP was measured over a 24 hr period every 20 minutes (AM) or every 45 minutes (PM). HTN: SBP ≥ 140 mmHg and/or DBP ≥ 90 mmHg and/or antihypertensive medication usage. | Discovery: 72 DMRs associated with 24 hr SBP (FDR < 0.05). 38 DMRs associated with SBP day (FDR < 0.05). 20 DMRs were associated with SBP night (FDR < 0.05). 12 DMRs associated with 24 hr DBP (FDR < 0.05). 9 DMRs associated with DBP day (FDR < 0.05). 4 DMRs associated with DBP night (FDR < 0.05). 22 DMRs associated with 24 hr PP (FDR < 0.05). 28 DMR associated with PP day (FDR < 0.05). 2 DMRs associated with PP night (FDR < 0.05). 34 DMRs associated with 24 MAP (FDR < 0.05). 7 DMRs associated with MAP day (FDR < 0.05). 5 DMRs associated with MAP night (FDR < 0.05). Validation: by BULLET-Seq |
Si et al. 2021 [198] | 8/9 | CKB | 56.4, 49.52, 982, China | 850k | PBC | 2 CpGs | SNX30, IMPDH2, PEMT | BP: measured twice using standardised protocols. | Participants in Q1 of methylation had lower SBP and DBP when compared to those in Q4 (P < 0.05) |
Sprague et al. 2022 [199] | 6/9 | Gen pop | 50.0, 67.1 (60.1-72.6)2, 112, Croatia | 850k | WB | 22 CpGs | C16orf72, BTN3A2, ACIN1, CUL2, MIEF1, TSTD2, NCBP1, CANT1, KRTCAP2, TRIM46 | BP: measured 3 times with the second and third measurements averaged. | 22 CpGs associated with SBP(q < 0.01). |
Wang et al. 2023 [169] | 6/9 | QTR | N/A3, 52 (40, 66), 60, China | RBBS | WB | SBP: 31 CpGs, 8 DMRs DBP: 43 CpGs, 12 DMRs | Top SBP CpGs: SRRM1P2, MIR3147 Top SBP DMRs: NFATC1, CADM2, LRAT, TUBA3C, LOC100507377 Top DBP CpGs: WNT3A, PLCH2, SIM1 Top DBP DMRs: WNT3A, NKX2-4, TMEM114, ZBTB25, CNOT10 | BP: measured 3 times with 1 minute interval and averaged. | 31 CpGs and 8 DMRs associated with SBP (P < 1E-04). 43 CpGs and 12 DMRs associated with DBP (P < 1E-04). |
Wu et al. 2022 [200] | 6/9 | TWB | 46.6, 49.0 (40.0–58.0)2, 1636, Taiwan | 850k | WB | 1 CpG | KLF14 | BP: indication of measurement. HTN: SBP ≥ 140 mmHg and/or DBP ≥ 90 mmHg and/or self-reported history of HTN. | 1 CpG associated with HTN (P = 0.0041), SBP (P = 0.0126), and Mean BP (P = 0.0212). |
Xiao et al. 2022 [71] | 8/9 | Gen pop | 42.9, 78.5 (16.1), 280, China | 850k | WBC | 11 DMRs | FMOD, TTC22, CEPZOS, HOPX, CCDC125, MIR886, HLA-DRB1, HOXA5, LINC00857, GLIPR1L2 | BP: measured 2-3 times after sat at rest for 5 minutes. HTN: SBP ≥ 140 mmHg and/or DBP ≥ 90 mmHg and/or antihypertensive medication usage. | 11 DMRs associated with HTN (FDR < 0.05). |
Yao et al. 2024 [201] | 6/9 | QTR | 53, 52 (40, 66), 60, China | RBBS | WB | SBP: 9 CpGs DBP: 33 CpGs | C10orf71-AS1, NDUFB5P1, KRT80, BAI2, ABCA2, PEX11G, FGF4, LMNB2, KDM4B, DNASE1/TRAP1, TFCP2L1, SLC25A19, HMCN2, RSPH6A, PTPRN2, PNPLA7, KRI1, ADORA2B, NAA60, STIL, CTNNBIP1, LINC01070, KIF26A, XKR6 | BP: measured using standard protocols | 9 CpGs associated with SBP (P < 0.05). 33 CpGs associated with DBP (P < 0.05). |
Zhang et al. 2022 [176] | 8/9 | HRS | 41.5, 70.5 (9.5), 3070, USA | 850k | WB | 9 CpGs | PHGDH, SLC7A11, LOC100132354, ZMIZ1, SLC1A5 | BP: measured 3 times with 45 s intervals between. HTN: antihypertensive medication usage. | In a fully adjusted model 5 CpGs (out of 13 previously reported CpG sites) were associated with SBP (P < 0.0038). 7 CpGs associated with DBP (P < 0.0038). |
