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Table 2 Mendelian randomization results for the associations between genetically predicted risk factors and kidney stones in two stages

From: Causal effects of modifiable risk factors on kidney stones: a bidirectional mendelian randomization study

Modifiable factorsa

Number of SNPsb

Discovery stagec

Replication staged

 

IVW OR (95% CI)

P-value

FDRe

IVW OR (95% CI)

P-value

FDRe

Cardiometabolic factors

 BMI

60

0.99 (0.77, 1.28)

0.951

0.972

1.16 (0.93, 1.45)

0.184

0.502

 WHR adjusted BMI

36

1.08 (0.84, 1.39)

0.529

0.737

1.5 (1.16, 1.94)

0.002

0.020

 Height

357

0.94 (0.86, 1.02)

0.123

0.319

0.91 (0.83, 0.99)

0.031

0.116

 Body fat percentage

5

0.72 (0.39, 1.33)

0.292

0.537

1.02 (0.28, 3.66)

0.979

0.979

 LDL cholesterol

286

1.05 (0.93, 1.18)

0.430

0.659

0.95 (0.85, 1.06)

0.369

0.692

 Total triglycerides

337

1.14 (1, 1.29)

0.048

0.201

1.12 (1.00, 1.26)

0.046

0.138

 Total cholesterol

338

1.11 (0.98, 1.24)

0.091

0.279

1.02 (0.91, 1.15)

0.695

0.825

 HDL cholesterol

381

1.02 (0.91, 1.15)

0.676

0.808

1.03 (0.92, 1.15)

0.627

0.825

 Fasting glucose

64

1.11 (0.86, 1.42)

0.427

0.659

1.21 (0.9, 1.64)

0.214

0.519

 Fasting insulin

35

2.38 (1.34, 4.22)

0.003

0.020

3.01 (1.8, 5.03)

2.54E−05

0.001

 Glycated hemoglobin (HbA1c)

70

0.94 (0.65, 1.36)

0.731

0.820

1.21 (0.83, 1.77)

0.312

0.669

 2 h glucose

9

0.93 (0.68, 1.27)

0.645

0.808

0.98 (0.72, 1.34)

0.889

0.953

 Type 2 diabetes mellitus

86

1.04 (0.97, 1.1)

0.287

0.537

1.08 (1, 1.16)

0.046

0.138

 SBP

10

1 (0.95, 1.04)

0.903

0.948

1 (0.94, 1.07)

0.950

0.979

 DBP

14

0.95 (0.9, 1.01)

0.079

0.279

0.98 (0.93, 1.04)

0.612

0.825

 Metabolic syndrome

60

0.94 (0.85, 1.04)

0.217

0.454

–

–

–

Lifestyle and dietary factors

 Smoking cessation

4

1.03 (0.66, 1.62)

0.897

0.948

1.18 (1.04, 1.33)

0.008

0.040

 Smoking initiation (ever regular vs never regular)

10

0.98 (0.74, 1.31)

0.907

0.948

0.9 (0.54, 1.51)

0.700

0.825

 Smoking cigarettes per day

9

1.29 (0.93, 1.79)

0.125

0.319

0.88 (0.62, 1.24)

0.453

0.799

 Alcohol drinks per week

5

2.33 (0.83, 6.48)

0.106

0.305

0.63 (0.25, 1.62)

0.336

0.672

 Years of education

47

0.79 (0.56, 1.1)

0.167

0.366

0.7 (0.53, 0.92)

0.011

0.047

 Caffeine consumption from Tea

22

0.3 (0.14, 0.67)

0.003

0.020

–

–

–

 Caffeine consumption from coffee or tea

41

0.82 (0.59, 1.14)

0.232

0.464

–

–

–

 Glucocorticoids (medication use)

19

0.94 (0.87, 1.01)

0.086

0.279

–

–

–

 Accelerometer-based PA (acceleration average)

8

1.03 (0.94, 1.13)

0.564

0.741

–

–

–

 Moderate-to-vigorous PA

17

1 (0.38, 2.64)

0.992

0.992

–

–

–

 Vigorous PA

7

0.49 (0.06, 3.77)

0.494

0.733

–

–

–

 Income before tax

25

0.24 (0.1, 0.59)

0.002

0.020

–

–

–

 Intelligence

157

0.86 (0.71, 1.05)

0.140

0.322

–

–

–

 Leisure sedentary behavior (computer use)

45

0.88 (0.51, 1.53)

0.660

0.808

–

–

–

 Driving

4

1.25 (0.98, 1.59)

0.067

0.257

–

–

–

 Leisure sedentary behavior (television watching)

125

1.12 (0.88, 1.43)

0.363

0.596

–

–

–

 Meat-related diet

14

0.78 (0.36, 1.69)

0.528

0.737

–

–

–

 Fish and plant-related diet

22

1.22 (0.63, 2.34)

0.553

0.741

–

–

–

Biochemical measures

 Serum vitamin B12

9

1.16 (1.01, 1.34)

0.039

0.198

0.99 (0.86, 1.13)

0.843

0.937

 Serum Vitamin C

7

1.12 (0.97, 1.3)

0.134

0.322

1.4 (0.81, 2.41)

0.225

0.519

 Serum 25-hydroxyvitamin D

6

1.55 (1.01, 2.36)

0.043

0.198

1.56 (1.13, 2.16)

0.007

0.040

 Serum magnesium

5

1.81E2 (2.57, 1.28E4)

0.017

0.098

4.84 (0.01, 2112.4)

0.611

0.825

 Serum calcium

5

1.21 (1.13, 1.29)

1.52E−08

3.50E−07

1.55 (1.21, 1.99)

0.001

0.015

 Serum phosphorus

5

0.47 (0.28, 0.78)

0.003

0.020

0.88 (0.43, 1.77)

0.715

0.825

 Serum CRP

17

0.88 (0.68, 1.15)

0.351

0.596

1.11 (0.81, 1.52)

0.526

0.825

 Serum uric acid

15

0.96 (0.78, 1.19)

0.730

0.820

0.97 (0.82, 1.15)

0.706

0.825

 Serum adiponectin

13

1.05 (0.82, 1.36)

0.685

0.808

1.07 (0.81, 1.41)

0.653

0.825

Urine measures

 Urine pH (pH pH > 5.0 VS ≤ 5.0)

3

0.28 (0.23, 0.35)

2.72E−29

1.25E−27

0.26 (0.1, 0.68)

0.006

0.040

 Urinary sodium

48

3.46 (1.59, 7.53)

0.002

0.020

–

–

–

 Urinary potassium

20

2.15 (0.45, 10.39)

0.341

0.596

–

–

–

  1. A two-sided p-value < 0.05 was considered statistically significant and shown in bold
  2. SNP single-nucleotide polymorphism, IVW inverse-variance weighted, FDR false discovery rates, OR odds ratio, CI confidence interval, SBP Systolic blood pressure, DBP Diastolic blood pressure, WHR waist-hip ratio, BMI body mass index, HDL high-density lipoprotein, LDL low-density lipoprotein, HDL high-density lipoprotein, PA physical activity, CRP C-reactive protein
  3. aIf the genetic instruments for exposures were obtained from UK Biobank, these exposures were not validated in the replication stage
  4. bSNPs represent the number of SNPs used within the instrument for each exposure after clumping, harmonization, and data extraction from the included GWAS
  5. cThe summary level data were extracted from the FinnGen consortium
  6. dThe summary level data were extracted from UK Biobank
  7. eAn FDR corrected P-value < 0.05 was considered statistically significant, indicating strong evidence of causality
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BMC Medical Genomics

ISSN: 1755-8794

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