Epigenome-wide analysis of DNA methylation and coronary heart disease: a nested case-control study

  1. Jiahui Si
  2. Songchun Yang
  3. Dianjianyi Sun
  4. Canqing Yu
  5. Yu Guo
  6. Yifen Lin
  7. Iona Y Millwood
  8. Robin G Walters
  9. Ling Yang
  10. Yiping Chen
  11. Huaidong Du
  12. Yujie Hua
  13. Jingchao Liu
  14. Junshi Chen
  15. Zhengming Chen
  16. Wei Chen
  17. Jun Lv  Is a corresponding author
  18. Liming Liang  Is a corresponding author
  19. Liming Li  Is a corresponding author
  20. China Kadoorie Biobank Collaborative Group
  1. Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, China
  2. Departments of Epidemiology and Biostatistics, Harvard T.H. Chan School of Public Health, United States
  3. Chinese Academy of Medical Sciences, China
  4. Department of Urology, West China Hospital, Sichuan University, China
  5. Medical Research Council Population Health Research Unit at the University of Oxford, United Kingdom
  6. Clinical Trial Service Unit & Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, United Kingdom
  7. NCDs Prevention and Control Department, Suzhou CDC, China
  8. NCDs Prevention and Control Department, Wuzhong CDC, China
  9. China National Center for Food Safety Risk Assessment, China
  10. Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, United States
  11. Key Laboratory of Molecular Cardiovascular Sciences (Peking University), Ministry of Education, China
  12. Peking University Institute of Environmental Medicine, China
2 figures, 9 tables and 8 additional files

Figures

Flowchart of the present study. CHD = coronary heart disease; QC = quality control; CpG = cytosine-phosphate-guanine; FDR = false discovery rate.
Figure 2 with 2 supplements
Heatmap of association with methylation network modules.

Correlation coefficient and -log10(P) (inside the bracket) were reported; the degree of -log10(p) is illustrated with the color legend. Linear regressions were fitted with inverse normal transformed module eigengene (ME) as dependent variables; coronary heart disease (CHD1) as indicator; and age, sex, education, marital status, smoking (SMK), drinking (DRK), physical activity (PA1 and PA2 as the second and third tertile respectively), diet score, body mass index, fasting time, study area and all surrogate variables as covariates.

Figure 2—figure supplement 1
Permutation test to confirm the validity of weighted gene co-methylation network analysis.

Correlation coefficient and -log10(P) (inside the bracket) were reported; the degree of -log10(P) is illustrated with the color legend. Linear regressions were fitted with inverse normal transformed module eigengene (ME) as dependent variables; shuffled case and control status (Permutation_case) as indicator; and age, sex, education, marital status, smoking (SMK), drinking (DRK), physical activity (PA1 and PA2 as the second and third tertile, respectively), diet score, body mass index (BMI), fasting time, study area and all surrogate variables as covariates.

Figure 2—figure supplement 2
Visualization of the brown module.

Genes in the center are the hub genes, pairwise correlation: 0.10–1.

Tables

Table 1
Age-, sex- and study area-adjusted baseline characteristics of 982 participants according to the case or control status.
Baseline characteristicsCases(n = 491)Controls(n = 491)P value
Age, year50.649.5-
Female, %43.643.6-
Urban area, %20.620.6-
Middle school and above, %43.445.60.730
Married, %90.494.70.028
Family history of heart attack, %6.94.70.127
Fasting time, h4.04.0-
Lifestyle factors
Daily tobacco smoker, %46.640.30.004
Daily alcohol drinker, %9.010.00.455
Physical activity, MET-h/day22.023.90.097
Diet score2.32.50.001
Vegetables 7 days/week, %92.791.00.278
Fruit 7 days/week, %9.413.80.030
Read meat <7 days/week, %79.280.00.600
Soybean product ≥4 days/week, %5.99.60.026
Fish ≥1 days/week, %24.628.90.022
Coarse grains ≥ 4 days/week, %22.824.60.047
Body mass index, kg/m223.923.30.002
Metabolic risk factors
Prevalent hypertension, %52.529.9< 0.001
Prevalent diabetes, %10.04.50.004
Blood lipids
Total cholesterol, mmol/L4.694.520.005
LDL-C, mmol/L2.352.210.003
HDL-C, mmol/L1.221.180.025
Triglyceride, mmol/L2.202.010.064
  1. The results are presented as means or percentages. P values were not showed for matched factors. MET = metabolic equivalent of task; LDL-C = low-density lipoprotein cholesterol; HDL-C = high-density lipoprotein cholesterol.

Table 2
Associations of 25 significant CpGs with the risk of coronary heart disease.
ChrPosition(hg19)CpGSDGeneRelation to geneEWASWGCNA*Odds Ratio (95% CI)
βPFDRModule-specific FDR
9115513036cg233988260.008SNX30TSS200–0.0031.57E-080.0121.05E-040.56 (0.45, 0.70)
349068057cg023865750.016IMPDH2TSS15000.0069.61E-080.0362.02E-042.00 (1.57, 2.56)
QRICH1Body
1937329330cg104009370.007ZNF790TSS2000.0021.09E-050.2880.0091.53 (1.24, 1.89)
12131758671cg205628210.022(RPS6P20 §)0.0052.42E-050.2880.0091.72 (1.28, 2.31)
634855635cg081066610.016TAF111stExon0.0033.16E-050.3050.0091.87 (1.35, 2.59)
ANKS1ATSS1500
1153203211cg116306100.019(MIR584§)0.0053.83E-050.3290.0091.77 (1.36, 2.32)
18426319cg203021710.018RERE5'UTR–0.0044.29E-050.3400.0090.55 (0.42, 0.73)
1163909324cg263341310.025MACROD1Body–0.0054.44E-050.3400.0090.53 (0.38, 0.73)
202444631cg075604080.018SNORD119TSS1500–0.0054.46E-050.3400.0090.60 (0.47, 0.77)
SNRPBBody
1946522185cg212105370.027MIR769TSS2000.0044.85E-050.3560.0092.18 (1.47, 3.23)
2060546782cg158334470.021(TAF4§)0.0065.55E-050.3750.0091.50 (1.20, 1.88)
1194963255cg025918260.005LOC100129203TSS2000.0025.70E-050.3750.0091.52 (1.23, 1.87)
7100861083cg166391380.006ZNHIT15'UTR/1stExon0.0026.46E-050.3750.0091.52 (1.24, 1.86)
PLOD3TSS200
627863042cg015454540.007(HIST1H2BO§)0.0027.29E-050.3780.0091.64 (1.26, 2.13)
1203242409cg072191030.008(CHIT1§)0.0027.35E-050.3780.0091.78 (1.28, 2.47)
2223994996cg056816430.018GUSBP11Body0.0047.42E-050.3780.0091.60 (1.24, 2.08)
288991375cg063585660.009RPIA1stExon–0.0027.74E-050.3850.0090.62 (0.48, 0.80)
2162273185cg195832110.016TBR11stExon–0.0037.97E-050.3850.0090.56 (0.41, 0.77)
203613189cg106438500.025ATRNBody0.0048.04E-050.3850.0091.97 (1.37, 2.82)
1717460905cg133114940.016PEMTBody–0.0058.50E-050.3970.0090.64 (0.52, 0.79)
1179852195cg117546700.009TOR1AIP1Body0.0018.84E-050.3980.0092.04 (1.40, 2.97)
1574928935cg057406320.014EDC3Body–0.0049.07E-050.3980.0090.62 (0.49, 0.78)
111972510cg084841000.023MRPL23Body–0.0049.19E-050.3980.0090.54 (0.40, 0.74)
152822428cg247921790.019CC2D1BBody0.0049.87E-050.4100.0091.79 (1.36, 2.35)
768973036cg227947120.021(LOC100507468§)–0.0061.10E-040.4130.0100.63 (0.50, 0.80)
  1. *

    cg23398826 in the Turquoise module, all other CpGs in the Brown module.

  2. Odds ratios were for per standard deviation increase in DNA methylation level.

  3. Effect sizes were calculated based on normalized methylation values, denoting the methylation difference between cases and controls.

  4. §

    For inter-genic CpG sites, R package FDb.InfiniumMethylation.hg19 was used to locate the nearest annotated gene.

  5. CpG = cytosine-phosphoguanine site; Chr = chromosome; EWAS = epigenome wide association; WGCNA = weighted gene co-methylation network analysis; FDR = false discovery rate; CI = confidence interval; TSS200 = within 200 bp from transcription start site; TSS1500 = within 1500 bp from transcription start site; Body = the CpG is in gene body; 1stExon = the first exon; and UTR = untranslated region.

Table 3
Associations between lifestyle factors and methylation level of identified CpGs, and the risk of coronary heart disease mediated through methylation level of CpG sites.

Effect size(SE)PMediation effect
Proportion mediated, %P
Smoking, no. of cigarettes/day



cg081066611.50E-04 (4.67E-05)0.00128.500.036
Diet score (ranging 0-6)



cg212105373.60E-03 (1.27E-03)0.0054.660.206
cg106438502.57E-03 (1.26E-03)0.042-6.910.088
cg057406321.37E-03 (6.88E-04)0.04711.300.068
Body mass index, kg/m2



cg203021713.90E-04 (1.67E-04)0.020-2.870.267
cg084841004.17E-04 (2.10E-04)0.048-1.910.373
  1. Linear regression was fitted by including all five lifestyle factors (smoking, alcohol consumption, physical activity, diet score, and body mass index) simultaneously in the same model, with methylation values as dependent variables, and age, sex, study area, fasting time, education level, marital status and batch as covariates. CpG = cytosine-phosphoguanine site; SE = standard error. Alcohol consumption and physical activity were not associated with any of the coronary heart disease-associated CpGs. Details were reported in the Table 3—source data 1.

Table 3—source data 1

Association between lifestyle factors and identified CpGs.

https://cdn.elifesciences.org/articles/68671/elife-68671-table3-data1-v2.docx
Table 4
Associations between quartile methylation level of identified CpGs and cardiometabolic traits, and the risk of coronary heart disease mediated through different cardiometabolic traits.


Quartile 1 vs. 4P for trendMediation effect
Effect size(SE)*PProportion mediated, %P
Systolic blood pressure, mmHg




cg23398826-6.410 (2.118)0.003<0.0017.650.003
cg13311494-6.580 (2.122)0.0020.02015.610.031
Diastolic blood pressure, mmHg




cg23398826-3.574 (1.218)0.003<0.0016.390.006
cg13311494-3.650 (1.221)0.0030.02912.380.045
Total cholesterol, mmol/L




cg263341310.197 (0.089)0.0260.003-31.620.168
cg057406320.163 (0.089)0.0660.013-3.210.126
cg212105370.175 (0.094)0.0640.027-8.190.197
cg19583211-0.064 (0.088)0.4660.0472.730.270
Cholesterol in LDL, mmol/L




cg263341310.110 (0.063)0.0790.007-32.140.135
cg203021710.107 (0.063)0.090.029-10.480.161
cg057406320.109 (0.063)0.0830.019-3.380.110
cg19583211-0.078 (0.062)0.2080.0203.600.210
cg13311494-0.117 (0.062)0.060.0273.700.208
cg212105370.126 (0.067)0.0590.044-8.550.177
Cholesterol in HDL, mmol/L




cg158334470.037 (0.026)0.1540.013-10.770.180
cg212105370.040 (0.027)0.1460.0197.300.235
Random blood glucose, mmol/L




cg104009370.551 (0.231)0.0170.0036.720.107
cg015454540.203 (0.234)0.3850.0069.580.097
cg117546700.466 (0.236)0.0490.00536.390.086
cg26334131-0.517 (0.234)0.0280.01832.700.109
cg072191030.578 (0.244)0.0180.0326.170.135
cg20302171-0.556 (0.234)0.0180.02715.770.123
  1. *

    Effect sizes denoted the differences of metabolic traits between the top and bottom quartile methylation level. Details of other quartiles were reported in the Table 4—source data 1.

  2. We added 15 and 10 mmHg to the measured systolic blood pressure and diastolic blood pressure respectively among participants who reported usage of blood pressure-lowering medications.

  3. Additionally adjusted for treatment of diabetes (yes or no) at baseline. Multivariable model was adjusted for: age, sex, education level, marital status, smoking, drinking, physical activity, dietary score, body mass index, fasting time, study area, and batch. The CpGs which were significantly associated with any metabolic risk factors were reported. Details of other CpGs were reported in the Supplementary tables. CpG = cytosine-phosphoguanine site; SE = standard error; LDL = low-density lipoprotein; HDL = high-density lipoprotein.

Table 4—source data 1

Association between quartile methylation level of identified CpGs and systolic blood pressure (mmHg).

https://cdn.elifesciences.org/articles/68671/elife-68671-table4-data1-v2.docx
Table 4—source data 2

Association between quartile methylation level of identified CpGs and diastolic blood pressure (mmHg).

https://cdn.elifesciences.org/articles/68671/elife-68671-table4-data2-v2.docx
Table 4—source data 3

Association between quartile methylation level of identified CpGs and total cholesterol (mmol/L).

https://cdn.elifesciences.org/articles/68671/elife-68671-table4-data3-v2.docx
Table 4—source data 4

Association between quartile methylation level of identified CpGs and cholesterol in low-density lipoprotein (mmol/L).

https://cdn.elifesciences.org/articles/68671/elife-68671-table4-data4-v2.docx
Table 4—source data 5

Association between quartile methylation level of identified CpGs and cholesterol in high-density lipoprotein (mmol/L).

https://cdn.elifesciences.org/articles/68671/elife-68671-table4-data5-v2.docx
Table 4—source data 6

Association between quartile methylation level of identified CpGs and random glucose (mmol/L).

https://cdn.elifesciences.org/articles/68671/elife-68671-table4-data6-v2.docx
Table 4—source data 7

Association between quartile methylation level of identified CpGs and triglyceride (mmol/L).

https://cdn.elifesciences.org/articles/68671/elife-68671-table4-data7-v2.docx
Author response table 1
OutcomeCpG namebeta coefficient in ourstudyp-value in our studybeta coefficient in the previous studyp-valuein theprevious studyGene
CHDcg22617878-5.89E-043.75E-01−0.37191.99E-08ATP2B2
cg138272098.39E-044.47E-010.2683.76E-08TGFBR1
cg14185717//−0.28781.38E-07BNC2
cg10307345-3.62E-031.88E-01−0.14801.86E-07PTPN5
cg13822123-6.12E-041.45E-010.41382.03E-07PSME4
cg232453161.04E-031.18E-01−0.46742.17E-07TSSC1
cg249772762.83E-034.60E-02−0.32562.54E-07GTF2I
cg244477881.17E-033.20E-01−0.26794.33E-07(PTBP1**)
cg084228031.35E-033.47E-010.19947.52E-07ITGB2
cg01751802-1.43E-035.85E-010.14739.35E-07KANK2
cg024493732.25E-059.77E-010.37159.98E-07FUT1
cg02683350-1.19E-033.62E-01−0.50621.55E-06ADAMTS2
cg058203122.89E-047.87E-010.50311.60E-06TRAPPC9
cg06639874-8.25E-046.41E-01−0.25061.83E-06MLPH
cg06582394-2.56E-031.49E-010.16571.90E-06CASR
cg02155262-4.62E-043.07E-010.4771.97E-06AGA
cg127663832.26E-033.11E-02−0.61941.98E-06UBR4
cg058924845.55E-059.60E-01−0.50202.01E-06MAD1L1
cg030318681.46E-048.65E-010.34612.29E-06ESD
cg25497530-5.63E-031.45E-03−0.22252.62E-06PTPRN2
cg06596307-2.06E-031.24E-01−0.41982.99E-06IGF1R
cg10702366-2.35E-031.47E-01−0.10933.09E-06FGGY
cg264701011.24E-034.46E-010.30523.09E-06(DLX2**)
cg260420241.66E-034.16E-01−0.31093.13E-06ZFAT
cg004661217.27E-044.26E-010.46463.16E-06ZNHIT6
cg04987302-1.96E-031.85E-01−0.33783.71E-06(OTX2-AS1**)
cg088534941.82E-047.27E-010.2214.03E-06RCHY1;THAP6
cg264677251.34E-032.02E-01−0.42254.22E-06SLCO3A1
cg064421929.07E-045.78E-01−0.52414.89E-06ZNF541
cg003933731.11E-032.92E-01−0.31564.91E-06ZNF518B
MIcg228717974.77E-046.85E-01−0.5995.29E-08CYFIP1
cg249772762.83E-034.60E-02−0.3669.97E-08GTF2I
cg185988611.43E-031.98E-01−0.6711.61E-07IRF9
cg097777767.95E-047.38E-010.2872.25E-07ZNF254
cg20545941-3.22E-046.69E-01−0.8852.47E-07MPPED1
cg199358459.61E-045.30E-01−0.3364.65E-07TNXB
cg24423782-2.37E-031.33E-01−0.3985.37E-07MIR182
cg003933731.11E-032.92E-01−0.4017.68E-07ZNF518B
cg004661217.27E-044.26E-010.4877.79E-07ZNHIT6
cg19227382//−0.5048.12E-07CDH23
cg03467256//−0.4088.33E-07HPCAL1
cg251968813.45E-047.46E-01−0.2691.05E-06(THBS1**)
cg023211129.68E-058.99E-010.391.08E-06(MNX1-AS1**)
cg003557992.79E-048.27E-01−0.2161.40E-06(LOC339529**)
cg17556588-1.20E-033.90E-01−0.1541.45E-06PRRG4
cg04987302-1.96E-031.85E-01−0.4281.50E-06(OTX2-AS1**)
cg07289306-1.45E-033.24E-020.6161.71E-06(MIR138-1**)
cg058924845.55E-059.60E-01−0.5511.84E-06MAD1L1
cg10702366-2.35E-031.47E-01−0.1502.11E-06FGGY
cg22618720//−0.4242.37E-06(MIR5095**)
cg140101943.46E-047.84E-01−0.4842.71E-06GUCA1B
cg138272098.39E-044.47E-010.2852.71E-06TGFBR1
cg24318598-1.75E-032.59E-01−0.2542.79E-06ANO1
cg070157751.01E-031.36E-010.4793.13E-06ZNHIT6
cg210181562.00E-031.39E-01−0.1353.17E-06(LINC01312**)
cg07475527-1.64E-032.46E-01−0.2253.77E-06(RCAN3**)
cg200005622.06E-038.15E-020.2183.93E-06SFTA3
cg074368073.57E-047.88E-01−0.7794.10E-06STAMBPL1; ACTA2
cg14029912-1.62E-031.39E-01−0.3674.29E-06(BHLHE40**)
cg228717974.77E-046.85E-01−0.5995.29E-08CYFIP1
Author response table 2
CpGBasic modelFull model
βPβP
cg23398826-0.0033.44E-08-0.0031.57E-08
cg023865750.0052.76E-070.0069.61E-08
cg104009370.0021.28E-050.0021.09E-05
cg205628210.0052.95E-050.0052.42E-05
cg081066610.0036.75E-050.0033.16E-05
cg116306100.0054.22E-050.0053.83E-05
cg20302171-0.0043.86E-05-0.0044.29E-05
cg26334131-0.0053.51E-05-0.0054.44E-05
cg07560408-0.0045.73E-05-0.0054.46E-05
cg212105370.00434.81E-050.0044.85E-05
cg158334470.0050.0001070.0065.55E-05
cg025918260.0024.97E-050.0025.70E-05
cg166391380.0020.0001220.0026.46E-05
cg015454540.0026.38E-050.0027.29E-05
cg072191030.0026.77E-050.0027.35E-05
cg056816430.0047.33E-050.0047.42E-05
cg06358566-0.0028.02E-05-0.0027.74E-05
cg19583211-0.0036.46E-05-0.0037.97E-05
cg106438500.0040.0001040.0048.04E-05
cg13311494-0.0048.04E-05-0.0058.50E-05
cg117546700.0010.0001010.0018.84E-05
cg05740632-0.0044.51E-05-0.0049.07E-05
cg08484100-0.0053.69E-05-0.0049.19E-05
cg247921790.0040.0001150.0049.87E-05
cg22794712-0.0050.000173-0.0061.10E-04
Author response table 3
Basic modelFull model
Proportion mediated, %Proportion mediated, %Proportion mediated, %Proportion mediated, %
Smoking, no. of cigarettes/daycg0810666126.800.03828.500.036
Diet score (ranging 0-6)cg212105373.890.2564.660.206
cg10643850-6.730.083-6.910.088
cg0574063211.030.06211.300.068
Body mass index, kg/m2cg20302171-2.900.269-2.870.267
cg08484100-2.320.304-1.910.373
Systolic blood pressure*, mmHg cg2339882613.210.0027.650.003
cg133114943.140.08215.610.031
Diastolic blood pressure*, mmHg cg2339882616.320.0026.390.006
cg133114943.800.07912.380.045
Total cholesterol, mmol/L cg26334131-5.670.449-31.620.168
cg05740632-33.040.020-3.210.126
cg21210537-6.700.169-8.190.197
cg195832118.670.1142.730.270
Cholesterol in LDL, mmol/L cg26334131-3.250.406-32.140.135
cg20302171-4.470.263-10.480.161
cg05740632-17.770.032-3.380.110
cg195832119.030.1753.600.210
cg133114949.020.1773.700.208
cg21210537-5.500.175-8.550.177
Cholesterol in HDL, mmol/L cg15833447-3.690.293-10.770.180
cg212105373.790.2607.300.235
Random blood glucose‡, mmol/L cg104009378.920.0566.720.107
cg015454546.080.1229.580.097
cg117546701.260.61336.390.086
cg263341311.500.61232.700.109
cg072191036.760.1026.170.135
cg203021712.490.39715.770.123
  1. * We added 15 and 10 mmHg to the measured systolic blood pressure and diastolic blood pressure respectively among participants who reported usage of blood pressure-lowering medications.

  2. ‡ Additionally adjusted for treatment of diabetes (yes or no) at baseline.

Author response table 4
Present studyGuarrera S, et al.13Agha Golareh, et al.1
No. of cases4912921,895
Sample size98258411,461
Mean age (years)50.152.464
Mean Follow-up time (years)7.612.911.2
Author response table 5
Model 1+adjusted for CC
Effect size(SE)PEffect size(SE)P
Smoking, no. of cigarettes/day cg081066611.50E-04 (4.67E-05)0.0019.00E-05 (4.39E-05)0.041
Systolic blood pressure, mmHg cg23398826-313.75 (91.72)<0.001-255.60 (94.88)0.007
cg13311494-108.86 (48.16)0.020-101.84 (47.02)0.031
Diastolic blood pressure, mmHg cg23398826-184.53 (52.74)<0.001-151.73 (55.07)0.006
cg13311494-59.54 (27.30)0.029-54.51 (27.30)0.046

Additional files

Supplementary file 1

Members of the China Kadoorie Biobank collaborative group.

https://cdn.elifesciences.org/articles/68671/elife-68671-supp1-v2.docx
Supplementary file 2

Detailed results and interpretation of the present study.

(A) Number of methylation markers associated with incident coronary heart disease across the range of P thresholds in the epigenome-wide association study. (B) Manhattan plot (A) and QQ plot (B) of the P values of the associations between each cytosine-phosphoguanine (CpG) site and incident coronary heart disease. In the Manhattan plot, the red line represents -log10(P) at false discovery rate (FDR) = 0.05. (C) Gene enrichment analysis of 2106 probes from the brown module which was significantly associated with coronary heart disease. (D) Associations of 25 significant CpGs with risk of coronary heart disease among 880 participants without usage of blood pressure lowering drug. (E) Association between quartile methylation level of identified CpGs and systolic blood pressure* (mmHg). (F) Association between quartile methylation level of identified CpGs and diastolic blood pressure* (mmHg). (G) The annotated or nearest annotated gene of the identified CHD-associated CpGs in our study and the previous GWAS finding.

https://cdn.elifesciences.org/articles/68671/elife-68671-supp2-v2.docx
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Source code 1

Single DNA methylation marker and incident CHD.

https://cdn.elifesciences.org/articles/68671/elife-68671-supp3-v2.zip
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Weighted gene co-methylation network and incident CHD.

https://cdn.elifesciences.org/articles/68671/elife-68671-supp4-v2.zip
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Mediation analysis.

https://cdn.elifesciences.org/articles/68671/elife-68671-supp5-v2.zip
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Baseline characteristics according to the case or controlstatus.

https://cdn.elifesciences.org/articles/68671/elife-68671-supp6-v2.zip
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STROBE Statement—Checklist of items that should be included in reports of case-control studies.

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  1. Jiahui Si
  2. Songchun Yang
  3. Dianjianyi Sun
  4. Canqing Yu
  5. Yu Guo
  6. Yifen Lin
  7. Iona Y Millwood
  8. Robin G Walters
  9. Ling Yang
  10. Yiping Chen
  11. Huaidong Du
  12. Yujie Hua
  13. Jingchao Liu
  14. Junshi Chen
  15. Zhengming Chen
  16. Wei Chen
  17. Jun Lv
  18. Liming Liang
  19. Liming Li
  20. China Kadoorie Biobank Collaborative Group
(2021)
Epigenome-wide analysis of DNA methylation and coronary heart disease: a nested case-control study
eLife 10:e68671.
https://doi.org/10.7554/eLife.68671