Table 1S. Number of people in each category by age group. Significant trend toward 
younger individuals reporting higher running volume, with more than 75% of the elite group 
falling between the ages of 18 and 35.
S1 Table.
Table 2S. Full running volume vs. blood biomarker results
Biomarker ANOVA p-value 
Trend p-value 
lowest mean
highest mean
Alb
<1e-16
<0.001
MVAM
PRO
ALT
<1e-16
<1e-16
SED
PRO
AST
<1e-16
<0.001
SED
PRO
B12
<0.001
<0.001
SED
PRO
BASOS
0.001
0.004
LVAM
PRO
BASOS_PCT
<0.001
0.156
SED
PRO
Ca
0.007
0.030
MVAM
PRO
Chol
<0.001
0.005
PRO
SED
CK
<1e-16
<1e-16
SED
PRO
Cor
<0.001
0.675
SED
PRO
D
<1e-16
0.424
SED
PRO
DHEAS
<0.001
<0.001
SED
PRO
EOS
<0.001
0.371
HVAM
SED
EOS_PCT
<0.001
0.137
HVAM
MVAM
FE
<0.001
0.119
SED
PRO
Fer
<1e-16
<1e-16
MVAM
SED
Fol
<1e-16
<0.001
SED
PRO
FT
<0.001
0.013
SED
PRO
GGT
<1e-16
<0.001
PRO
SED
Glu
0.087
0.184
PRO
SED
Hb
0.002
<0.001
MVAM
PRO
HCT
0.053
0.055
MVAM
PRO
HDL
<1e-16
<0.001
SED
PRO
HbA1c
<0.001
0.010
PRO
SED
hsCRP
<0.001
0.176
PRO
SED
K
<1e-16
<0.001
SED
LVAM
LDL
<0.001
0.006
PRO
SED
LYMPHS
<0.001
0.008
PRO
SED
LYMPHS_PCT
<1e-16
0.417
SED
PRO
Biomarker ANOVA p-value 
Trend p-value 
lowest mean
highest mean
MCH
0.197
0.077
SED
PRO
MCHC
<1e-16
0.276
SED
PRO
MCV
<0.001
<0.001
SED
PRO
Mg
<0.001
0.276
PRO
SED
MONOS
<0.001
0.175
PRO
SED
MONOS_PCT
<0.001
0.137
SED
LVAM
MPV
0.058
0.089
SED
HVAM
Na
<1e-16
0.622
HVAM
SED
NEUT
<0.001
0.007
PRO
SED
NEUT_PCT
<0.001
0.764
PRO
SED
PLT
<0.001
0.058
LVAM
SED
RBC
0.016
0.880
MVAM
SED
RBC_Mg
<0.001
0.773
PRO
SED
RDW
<1e-16
0.002
PRO
SED
SHBG
<1e-16
0.004
SED
PRO
Tes
<1e-16
0.675
MVAM
LVAM
Tg
<1e-16
<1e-16
PRO
SED
TIBC
<0.001
0.417
LVAM
MVAM
TS
<1e-16
0.298
SED
PRO
WBC
<1e-16
<1e-16
PRO
SED
S2 Table.
Table 3S. 2S-MR results with BMI as the exposure and select biomarkers as 
outcomes
S3.
S3 Table.
Table 4S. 2S-MR results with BMI with biomarkers as exposures and BMI as outcome 
to assess reverse causality
id.exposure
id.outcome outcome
exposure
method
nsnp
b
se
pval
ebi-a-
GCST004631
ukb-a-248
Body mass index (BMI) || 
id:ukb-a-248
Basophil percentage of white cells 
|| id:ebi-a-GCST004631
MR Egger
55
0.02850274
0.03058163
0.35555179
ebi-a-
GCST004631
ukb-a-248
Body mass index (BMI) || 
id:ukb-a-248
Basophil percentage of white cells 
|| id:ebi-a-GCST004631
Weighted 
median
55
0.01115946
0.01802141
0.53576264
ebi-a-
GCST004631
ukb-a-248
Body mass index (BMI) || 
id:ukb-a-248
Basophil percentage of white cells 
|| id:ebi-a-GCST004631
Inverse 
variance 
weighted
55
-0.0133255
0.01548404
0.38946137
ebi-a-
GCST004631
ukb-a-248
Body mass index (BMI) || 
id:ukb-a-248
Basophil percentage of white cells 
|| id:ebi-a-GCST004631
Simple mode
55
0.00553647
0.03733532
0.88266604
ebi-a-
GCST004631
ukb-a-248
Body mass index (BMI) || 
id:ukb-a-248
Basophil percentage of white cells 
|| id:ebi-a-GCST004631
Weighted mode 55
-0.0005482
0.02054445
0.97881084
id.exposure
id.outcome
outcome
exposure
method
nsnp
b
se
pval
ieu-a-1012
ukb-a-248
Body mass index (BMI) || 
id:ukb-a-248
Plasma cortisol || id:ieu-a-1012
Wald ratio
1
-0.0162841
0.0285215
0.56803913
id.exposure
id.outcome
outcome
exposure
method
nsnp
b
se
pval
ieu-a-1050
ukb-a-248
Body mass index (BMI) || 
id:ukb-a-248
Ferritin || id:ieu-a-1050
MR Egger
4
-0.0692185
0.02954547
0.14388806
ieu-a-1050
ukb-a-248
Body mass index (BMI) || 
id:ukb-a-248
Ferritin || id:ieu-a-1050
Weighted 
median
4
-0.0458501
0.01819113
0.01171994
ieu-a-1050
ukb-a-248
Body mass index (BMI) || 
id:ukb-a-248
Ferritin || id:ieu-a-1050
Inverse 
variance 
weighted
4
-0.0401901
0.01571805
0.01055975
ieu-a-1050
ukb-a-248
Body mass index (BMI) || 
id:ukb-a-248
Ferritin || id:ieu-a-1050
Simple mode
4
-0.040832
0.02570683
0.21040991
ieu-a-1050
ukb-a-248
Body mass index (BMI) || 
id:ukb-a-248
Ferritin || id:ieu-a-1050
Weighted mode 4
-0.0508659
0.01904314
0.07562034
S4.
S4 Table.
id.exposure
id.outcome
outcome
exposure
method
nsnp
b
se
pval
ukb-b-11349
ieu-b-40
body mass index || id:ieu-b-
40
Folate || id:ukb-b-
11349
Wald ratio
1
0.04546597
0.058838
32
0.439683
8
id.exposure
id.outcome
outcome
exposure
method
nsnp
b
se
pval
ieu-b-114
ukb-a-248
Body mass index (BMI) || 
id:ukb-a-248
Fasting glucose || 
id:ieu-b-114
MR Egger
30
-0.0453952
0.113428
53
0.692038
95
ieu-b-114
ukb-a-248
Body mass index (BMI) || 
id:ukb-a-248
Fasting glucose || 
id:ieu-b-114
Weighted median
30
0.00266784
0.031883
98
0.933316
16
ieu-b-114
ukb-a-248
Body mass index (BMI) || 
id:ukb-a-248
Fasting glucose || 
id:ieu-b-114
Inverse variance weighted
30
-0.0341858
0.052964
48
0.518637
21
ieu-b-114
ukb-a-248
Body mass index (BMI) || 
id:ukb-a-248
Fasting glucose || 
id:ieu-b-114
Simple mode
30
-0.01322
0.067068
73
0.845115
55
ieu-b-114
ukb-a-248
Body mass index (BMI) || 
id:ukb-a-248
Fasting glucose || 
id:ieu-b-114
Weighted mode
30
0.00016512
0.029158
44
0.995520
48
id.exposure
id.outcome
outcome
exposure
method
nsnp
b
se
pval
ieu-a-270
ukb-a-248
Body mass index (BMI) || 
id:ukb-a-248
Haemoglobin 
concentration || 
id:ieu-a-270
MR Egger
15
0.00144021
0.07587
258
0.98514
372
ieu-a-270
ukb-a-248
Body mass index (BMI) || 
id:ukb-a-248
Haemoglobin 
concentration || 
id:ieu-a-270
Weighted median
15
0.01307681
0.02023
195
0.51805
628
ieu-a-270
ukb-a-248
Body mass index (BMI) || 
id:ukb-a-248
Haemoglobin 
concentration || 
id:ieu-a-270
Inverse variance weighted
15
-0.0334432
0.02660
806
0.20879
683
ieu-a-270
ukb-a-248
Body mass index (BMI) || 
id:ukb-a-248
Haemoglobin 
concentration || 
id:ieu-a-270
Simple mode
15
-0.1129022
0.05448
673
0.05720
502
ieu-a-270
ukb-a-248
Body mass index (BMI) || 
id:ukb-a-248
Haemoglobin 
concentration || 
id:ieu-a-270
Weighted mode
15
0.01648048
0.02138
074
0.45363
255
id.exposure
id.outcome
outcome
exposure
method
nsnp
b
se
pval
ieu-b-103
ukb-a-248
Body mass index (BMI) || 
id:ukb-a-248
HbA1C || id:ieu-b-
103
MR Egger
11
0.01268313
0.08396
0.88325
885
ieu-b-103
ukb-a-248
Body mass index (BMI) || 
id:ukb-a-248
HbA1C || id:ieu-b-
103
Weighted median
11
-0.0069654
0.03248
061
0.83019
839
ieu-b-103
ukb-a-248
Body mass index (BMI) || 
id:ukb-a-248
HbA1C || id:ieu-b-
103
Inverse variance weighted
11
0.0283815
0.03446
064
0.41017
145
ieu-b-103
ukb-a-248
Body mass index (BMI) || 
id:ukb-a-248
HbA1C || id:ieu-b-
103
Simple mode
11
-0.0257779
0.06293
863
0.69075
483
ieu-b-103
ukb-a-248
Body mass index (BMI) || 
id:ukb-a-248
HbA1C || id:ieu-b-
103
Weighted mode
11
-0.0208929
0.03914
067
0.60514
756
id.exposure
id.outcome
outcome
exposure
method
nsnp
b
se
pval
ieu-a-275
ukb-a-248
Body mass index (BMI) || 
id:ukb-a-248
Red blood cell count 
|| id:ieu-a-275
MR Egger
26
0.26135491
0.14952
437
0.09326
378
ieu-a-275
ukb-a-248
Body mass index (BMI) || 
id:ukb-a-248
Red blood cell count 
|| id:ieu-a-275
Weighted median
26
0.08455861
0.04638
846
0.06832
803
ieu-a-275
ukb-a-248
Body mass index (BMI) || 
id:ukb-a-248
Red blood cell count 
|| id:ieu-a-275
Inverse variance weighted
26
-0.0072778
0.05705
404
0.89849
796
ieu-a-275
ukb-a-248
Body mass index (BMI) || 
id:ukb-a-248
Red blood cell count 
|| id:ieu-a-275
Simple mode
26
0.09054068
0.07897
524
0.26246
646
ieu-a-275
ukb-a-248
Body mass index (BMI) || 
id:ukb-a-248
Red blood cell count 
|| id:ieu-a-275
Weighted mode
26
0.09962869
0.04750
758
0.04626
112
id.exposure
id.outcome
outcome
exposure
method
nsnp
b
se
pval
ebi-a-
GCST005068
ieu-b-40
body mass index || id:ieu-b-
40
LDL cholesterol || 
id:ebi-a-GCST005068
MR Egger
4
0.01267769
0.05816
618
0.84767
998
ebi-a-
GCST005068
ieu-b-40
body mass index || id:ieu-b-
40
LDL cholesterol || 
id:ebi-a-GCST005068
Weighted median
4
-0.0332107
0.01134
854
0.00342
875
ebi-a-
GCST005068
ieu-b-40
body mass index || id:ieu-b-
40
LDL cholesterol || 
id:ebi-a-GCST005068
Inverse variance weighted
4
-0.0320938
0.00863
712
0.00020
257
ebi-a-
GCST005068
ieu-b-40
body mass index || id:ieu-b-
40
LDL cholesterol || 
id:ebi-a-GCST005068
Simple mode
4
-0.036639
0.01673
254
0.11628
833
ebi-a-
GCST005068
ieu-b-40
body mass index || id:ieu-b-
40
LDL cholesterol || 
id:ebi-a-GCST005068
Weighted mode
4
-0.034971
0.01482
963
0.09956
398
id.exposure
id.outcome
outcome
exposure
method
nsnp
b
se
pval
ebi-a-
GCST90002336
ukb-a-248
Body mass index (BMI) || 
id:ukb-a-248
Mean corpuscular 
volume || id:ebi-a-
GCST90002336
MR Egger
9
0.01627788
0.03256
415
0.63249
338
ebi-a-
GCST90002336
ukb-a-248
Body mass index (BMI) || 
id:ukb-a-248
Mean corpuscular 
volume || id:ebi-a-
GCST90002336
Weighted median
9
-0.0169769
0.01096
864
0.12167
813
ebi-a-
GCST90002336
ukb-a-248
Body mass index (BMI) || 
id:ukb-a-248
Mean corpuscular 
volume || id:ebi-a-
GCST90002336
Inverse variance weighted
9
-0.0212777
0.01246
612
0.08785
201
ebi-a-
GCST90002336
ukb-a-248
Body mass index (BMI) || 
id:ukb-a-248
Mean corpuscular 
volume || id:ebi-a-
GCST90002336
Simple mode
9
-0.0220168
0.01637
922
0.21575
632
ebi-a-
GCST90002336
ukb-a-248
Body mass index (BMI) || 
id:ukb-a-248
Mean corpuscular 
volume || id:ebi-a-
GCST90002336
Weighted mode
9
-0.0231087
0.01392
193
0.13552
035
id.exposure
id.outcome
outcome
exposure
method
nsnp
b
se
pval
ieu-a-1008
ukb-a-248
Body mass index (BMI) || 
id:ukb-a-248
Platelet count || 
id:ieu-a-1008
MR Egger
32
-0.0006727
0.00070
143
0.34517
459
ieu-a-1008
ukb-a-248
Body mass index (BMI) || 
id:ukb-a-248
Platelet count || 
id:ieu-a-1008
Weighted median
32
0.00013472
0.00021
428
0.52954
228
ieu-a-1008
ukb-a-248
Body mass index (BMI) || 
id:ukb-a-248
Platelet count || 
id:ieu-a-1008
Inverse variance weighted
32
-0.0003268
0.00024
878
0.18895
678
ieu-a-1008
ukb-a-248
Body mass index (BMI) || 
id:ukb-a-248
Platelet count || 
id:ieu-a-1008
Simple mode
32
9.63E-05
0.00034
761
0.78352
525
ieu-a-1008
ukb-a-248
Body mass index (BMI) || 
id:ukb-a-248
Platelet count || 
id:ieu-a-1008
Weighted mode
32
0.00011659
0.00024
456
0.63688
891
id.exposure
id.outcome
outcome
exposure
method
nsnp
b
se
pval
ieu-a-275
ukb-a-248
Body mass index (BMI) || 
id:ukb-a-248
Red blood cell count 
|| id:ieu-a-275
MR Egger
26
0.26135491
0.14952
437
0.09326
378
ieu-a-275
ukb-a-248
Body mass index (BMI) || 
id:ukb-a-248
Red blood cell count 
|| id:ieu-a-275
Weighted median
26
0.08455861
0.04591
029
0.06550
111
ieu-a-275
ukb-a-248
Body mass index (BMI) || 
id:ukb-a-248
Red blood cell count 
|| id:ieu-a-275
Inverse variance weighted
26
-0.0072778
0.05705
404
0.89849
796
ieu-a-275
ukb-a-248
Body mass index (BMI) || 
id:ukb-a-248
Red blood cell count 
|| id:ieu-a-275
Simple mode
26
0.09054068
0.07653
474
0.24793
721
ieu-a-275
ukb-a-248
Body mass index (BMI) || 
id:ukb-a-248
Red blood cell count 
|| id:ieu-a-275
Weighted mode
26
0.09962869
0.04605
998
0.04030
183
id.exposure
id.outcome
outcome
exposure
method
nsnp
b
se
pval
ebi-a-
GCST006804
ukb-a-248
Body mass index (BMI) || 
id:ukb-a-248
Red cell distribution 
width || id:ebi-a-
GCST006804
MR Egger
122
-0.0341912
0.03423
066
0.31987
855
ebi-a-
GCST006804
ukb-a-248
Body mass index (BMI) || 
id:ukb-a-248
Red cell distribution 
width || id:ebi-a-
GCST006804
Weighted median
122
0.01563428
0.00970
492
0.10718
764
ebi-a-
GCST006804
ukb-a-248
Body mass index (BMI) || 
id:ukb-a-248
Red cell distribution 
width || id:ebi-a-
GCST006804
Inverse variance weighted
122
0.0300081
0.01723
486
0.08166
104
ebi-a-
GCST006804
ukb-a-248
Body mass index (BMI) || 
id:ukb-a-248
Red cell distribution 
width || id:ebi-a-
GCST006804
Simple mode
122
0.01857783
0.02026
892
0.36119
26
ebi-a-
GCST006804
ukb-a-248
Body mass index (BMI) || 
id:ukb-a-248
Red cell distribution 
width || id:ebi-a-
GCST006804
Weighted mode
122
0.01128028
0.01217
303
0.35594
689
id.exposure
id.outcome
outcome
exposure
method
nsnp
b
se
pval
ieu-a-302
ukb-a-248
Body mass index (BMI) || 
id:ukb-a-248
Triglycerides || 
id:ieu-a-302
MR Egger
55
-0.0445751
0.03601
334
0.22126
815
ieu-a-302
ukb-a-248
Body mass index (BMI) || 
id:ukb-a-248
Triglycerides || 
id:ieu-a-302
Weighted median
55
-0.0315603
0.01590
831
0.04726
817
ieu-a-302
ukb-a-248
Body mass index (BMI) || 
id:ukb-a-248
Triglycerides || 
id:ieu-a-302
Inverse variance weighted
55
-0.0214287
0.02233
545
0.33735
629
ieu-a-302
ukb-a-248
Body mass index (BMI) || 
id:ukb-a-248
Triglycerides || 
id:ieu-a-302
Simple mode
55
-0.0456892
0.02952
211
0.12755
31
ieu-a-302
ukb-a-248
Body mass index (BMI) || 
id:ukb-a-248
Triglycerides || 
id:ieu-a-302
Weighted mode
55
-0.0297723
0.01209
893
0.01709
375
id.exposure
id.outcome
outcome
exposure
method
nsnp
b
se
pval
ieu-b-30
ukb-a-248
Body mass index (BMI) || 
id:ukb-a-248
white blood cell 
count || id:ieu-b-30
MR Egger
475
-0.0347487
0.02445
633
0.15602
056
ieu-b-30
ukb-a-248
Body mass index (BMI) || 
id:ukb-a-248
white blood cell 
count || id:ieu-b-30
Weighted median
475
-0.0307482
0.01204
555
0.01069
025
ieu-b-30
ukb-a-248
Body mass index (BMI) || 
id:ukb-a-248
white blood cell 
count || id:ieu-b-30
Inverse variance weighted
475
-0.040535
0.01168
163
0.00052
05
ieu-b-30
ukb-a-248
Body mass index (BMI) || 
id:ukb-a-248
white blood cell 
count || id:ieu-b-30
Simple mode
475
0.00133145
0.03782
675
0.97193
623
ieu-b-30
ukb-a-248
Body mass index (BMI) || 
id:ukb-a-248
white blood cell 
count || id:ieu-b-30
Weighted mode
475
-0.0184754
0.02085
621
0.37614
876
id.exposure
id.outcome
outcome
exposure
method
nsnp
b
se
pval
ukb-d-
30830_raw
ieu-b-40
body mass index || id:ieu-b-
40
SHBG || id:ukb-d-
30830_raw
MR Egger
135
0.00121356
0.00180
979
0.50366
715
ukb-d-
30830_raw
ieu-b-40
body mass index || id:ieu-b-
40
SHBG || id:ukb-d-
30830_raw
Weighted median
135
0.00102542
0.00037
386
0.00609
279
ukb-d-
30830_raw
ieu-b-40
body mass index || id:ieu-b-
40
SHBG || id:ukb-d-
30830_raw
Inverse variance weighted
135
-0.002129
0.00115
3
0.06482
013
ukb-d-
30830_raw
ieu-b-40
body mass index || id:ieu-b-
40
SHBG || id:ukb-d-
30830_raw
Simple mode
135
-0.0011256
0.00124
723
0.36841
147
id.exposure
id.outcome
outcome
exposure
method
nsnp
b
se
pval
ebi-a-GCST006098
ebi-a-
GCST005068
LDL cholesterol || id:ebi-a-
GCST005068
Vigorous physical activity 
|| id:ebi-a-GCST006098
MR Egger
7
4.55735741
5.397582
61
0.437005
89
ebi-a-GCST006098
ebi-a-
GCST005068
LDL cholesterol || id:ebi-a-
GCST005068
Vigorous physical activity 
|| id:ebi-a-GCST006098
Weighted median
7
-0.6208293
0.838434
47
0.459019
39
ebi-a-GCST006098
ebi-a-
GCST005068
LDL cholesterol || id:ebi-a-
GCST005068
Vigorous physical activity 
|| id:ebi-a-GCST006098
Inverse variance weighted
7
-0.2426177
0.660161
46
0.713236
61
ebi-a-GCST006098
ebi-a-
GCST005068
LDL cholesterol || id:ebi-a-
GCST005068
Vigorous physical activity 
|| id:ebi-a-GCST006098
Simple mode
7
-1.231375
1.532513
13
0.452333
86
ebi-a-GCST006098
ebi-a-
GCST005068
LDL cholesterol || id:ebi-a-
GCST005068
Vigorous physical activity 
|| id:ebi-a-GCST006098
Weighted mode
7
-1.0821029
1.017395
34
0.328430
07
ebi-a-GCST006098
ieu-a-1050
Ferritin || id:ieu-a-1050
Vigorous physical activity 
|| id:ebi-a-GCST006098
MR Egger
5
-5.2248204
5.495151
03
0.411848
23
ebi-a-GCST006098
ieu-a-1050
Ferritin || id:ieu-a-1050
Vigorous physical activity 
|| id:ebi-a-GCST006098
Weighted median
5
-0.7040971
0.647521
49
0.276872
22
ebi-a-GCST006098
ieu-a-1050
Ferritin || id:ieu-a-1050
Vigorous physical activity 
|| id:ebi-a-GCST006098
Inverse variance weighted
5
-0.1408587
0.767230
61
0.854332
25
ebi-a-GCST006098
ieu-a-1050
Ferritin || id:ieu-a-1050
Vigorous physical activity 
|| id:ebi-a-GCST006098
Simple mode
5
-0.8515134
0.843286
04
0.369732
73
ebi-a-GCST006098
ieu-a-1050
Ferritin || id:ieu-a-1050
Vigorous physical activity 
|| id:ebi-a-GCST006098
Weighted mode
5
-0.9327437
0.769158
52
0.291972
96
ebi-a-GCST006098
ieu-a-302
Triglycerides || id:ieu-a-302
Vigorous physical activity 
|| id:ebi-a-GCST006098
MR Egger
5
-1.4775783
1.334354
04
0.348955
32
ebi-a-GCST006098
ieu-a-302
Triglycerides || id:ieu-a-302
Vigorous physical activity 
|| id:ebi-a-GCST006098
Weighted median
5
-0.1485007
0.262002
58
0.570856
3
ebi-a-GCST006098
ieu-a-302
Triglycerides || id:ieu-a-302
Vigorous physical activity 
|| id:ebi-a-GCST006098
Inverse variance weighted
5
-0.0745059
0.221142
62
0.736182
24
ebi-a-GCST006098
ieu-a-302
Triglycerides || id:ieu-a-302
Vigorous physical activity 
|| id:ebi-a-GCST006098
Simple mode
5
-0.1338663
0.368514
73
0.734794
89
ebi-a-GCST006098
ieu-a-302
Triglycerides || id:ieu-a-302
Vigorous physical activity 
|| id:ebi-a-GCST006098
Weighted mode
5
-0.1563444
0.328858
88
0.659289
19
ebi-a-GCST006098
ukb-b-11349
Folate || id:ukb-b-11349
Vigorous physical activity 
|| id:ebi-a-GCST006098
MR Egger
7
0.44992252
2.058173
78
0.835602
06
ebi-a-GCST006098
ukb-b-11349
Folate || id:ukb-b-11349
Vigorous physical activity 
|| id:ebi-a-GCST006098
Weighted median
7
-0.2016639
0.320053
64
0.528633
09
ebi-a-GCST006098
ukb-b-11349
Folate || id:ukb-b-11349
Vigorous physical activity 
|| id:ebi-a-GCST006098
Inverse variance weighted
7
-0.2577298
0.244615
28
0.292060
17
ebi-a-GCST006098
ukb-b-11349
Folate || id:ukb-b-11349
Vigorous physical activity 
|| id:ebi-a-GCST006098
Simple mode
7
0.0568742
0.467024
35
0.907049
56
ebi-a-GCST006098
ukb-b-11349
Folate || id:ukb-b-11349
Vigorous physical activity 
|| id:ebi-a-GCST006098
Weighted mode
7
0.07601041
0.465339
68
0.875610
65
Table 5S. 2S-MR results with vigorous physical activity as exposure and blood biomarkers as outcomes
S5.
S5 Table.
ebi-a-GCST006098
ukb-d-
30070_irnt
Red blood cell (erythrocyte) 
distribution width || id:ukb-d-
30070_irnt
Vigorous physical activity 
|| id:ebi-a-GCST006098
MR Egger
7
1.57820562
1.795700
92
0.419691
32
ebi-a-GCST006098
ukb-d-
30070_irnt
Red blood cell (erythrocyte) 
distribution width || id:ukb-d-
30070_irnt
Vigorous physical activity 
|| id:ebi-a-GCST006098
Weighted median
7
-0.0549663
0.143906
26
0.702491
75
ebi-a-GCST006098
ukb-d-
30070_irnt
Red blood cell (erythrocyte) 
distribution width || id:ukb-d-
30070_irnt
Vigorous physical activity 
|| id:ebi-a-GCST006098
Inverse variance weighted
7
-0.2321729
0.213298
82
0.276380
26
ebi-a-GCST006098
ukb-d-
30070_irnt
Red blood cell (erythrocyte) 
distribution width || id:ukb-d-
30070_irnt
Vigorous physical activity 
|| id:ebi-a-GCST006098
Simple mode
7
-0.0408618
0.177334
68
0.825419
27
ebi-a-GCST006098
ukb-d-
30070_irnt
Red blood cell (erythrocyte) 
distribution width || id:ukb-d-
30070_irnt
Vigorous physical activity 
|| id:ebi-a-GCST006098
Weighted mode
7
-0.0920344
0.182147
56
0.631385
89
ebi-a-GCST006098
ukb-d-
30830_irnt
SHBG || id:ukb-d-30830_irnt
Vigorous physical activity 
|| id:ebi-a-GCST006098
MR Egger
7
0.46503747
1.973712
9
0.823077
52
ebi-a-GCST006098
ukb-d-
30830_irnt
SHBG || id:ukb-d-30830_irnt
Vigorous physical activity 
|| id:ebi-a-GCST006098
Weighted median
7
0.11870029
0.151914
89
0.434590
52
ebi-a-GCST006098
ukb-d-
30830_irnt
SHBG || id:ukb-d-30830_irnt
Vigorous physical activity 
|| id:ebi-a-GCST006098
Inverse variance weighted
7
0.33282495
0.213695
39
0.119358
06
ebi-a-GCST006098
ukb-d-
30830_irnt
SHBG || id:ukb-d-30830_irnt
Vigorous physical activity 
|| id:ebi-a-GCST006098
Simple mode
7
0.07719013
0.190096
22
0.698784
8
ebi-a-GCST006098
ukb-d-
30830_irnt
SHBG || id:ukb-d-30830_irnt
Vigorous physical activity 
|| id:ebi-a-GCST006098
Weighted mode
7
0.08827653
0.182289
32
0.645365
99
id.exposure
id.outcome
outcome
exposure
Egger intercept se
pval
ebi-a-GCST006098
ebi-a-
GCST005068
LDL cholesterol || id:ebi-a-
GCST005068
Vigorous physical activity 
|| id:ebi-a-GCST006098
-0.0463331
0.051710
55
0.411305
82
ebi-a-GCST006098
ieu-a-1050
Ferritin || id:ieu-a-1050
Vigorous physical activity 
|| id:ebi-a-GCST006098
0.04824757
0.051622
26
0.418926
33
ebi-a-GCST006098
ieu-a-302
Triglycerides || id:ieu-a-302
Vigorous physical activity 
|| id:ebi-a-GCST006098
0.01391277
0.013048
39
0.364507
21
ebi-a-GCST006098
ukb-b-11349
Folate || id:ukb-b-11349
Vigorous physical activity 
|| id:ebi-a-GCST006098
-0.0065813
0.019005
84
0.743228
24
ebi-a-GCST006098
ukb-d-
30070_irnt
Red blood cell (erythrocyte) 
distribution width || id:ukb-d-
30070_irnt
Vigorous physical activity 
|| id:ebi-a-GCST006098
-0.0168346
0.016580
53
0.356535
74
ebi-a-GCST006098
ukb-d-
30830_irnt
SHBG || id:ukb-d-30830_irnt
Vigorous physical activity 
|| id:ebi-a-GCST006098
-0.0012295
0.018225
48
0.948828
18
Tests for horizontal pleiotropy
id.exposure
id.outcome
outcome
exposure
method
nsn
p
b
se
pval
ebi-a-
GCST006098
ukb-b-10217
Sweets intake || id:ukb-b-
10217
Vigorous physical activity || id:ebi-
a-GCST006098
MR Egger
7
-
0.0903539
1.5078935
0.95454
011
ebi-a-
GCST006098
ukb-b-10217
Sweets intake || id:ukb-b-
10217
Vigorous physical activity || id:ebi-
a-GCST006098
Weighted median
7
-
0.2367422
0.21224606
0.26467
304
ebi-a-
GCST006098
ukb-b-10217
Sweets intake || id:ukb-b-
10217
Vigorous physical activity || id:ebi-
a-GCST006098
Inverse variance weighted
7
-
0.1760505
0.17921106
0.32592
043
ebi-a-
GCST006098
ukb-b-10217
Sweets intake || id:ukb-b-
10217
Vigorous physical activity || id:ebi-
a-GCST006098
Simple mode
7
-
0.2770321
0.31802813
0.41719
033
ebi-a-
GCST006098
ukb-b-10217
Sweets intake || id:ukb-b-
10217
Vigorous physical activity || id:ebi-
a-GCST006098
Weighted mode
7
-
0.2596458
0.31161898
0.43662
814
ebi-a-
GCST006098
ukb-b-11679
Type of special diet 
followed: Vegetarian || 
id:ukb-b-11679
Vigorous physical activity || id:ebi-
a-GCST006098
MR Egger
6
0.3098933
2
0.88272515
0.74325
054
ebi-a-
GCST006098
ukb-b-11679
Type of special diet 
followed: Vegetarian || 
id:ukb-b-11679
Vigorous physical activity || id:ebi-
a-GCST006098
Weighted median
6
0.0220304
6
0.0642637
0.73173
884
ebi-a-
GCST006098
ukb-b-11679
Type of special diet 
followed: Vegetarian || 
id:ukb-b-11679
Vigorous physical activity || id:ebi-
a-GCST006098
Inverse variance weighted
6
0.0230808
9
0.04874316
0.63584
178
ebi-a-
GCST006098
ukb-b-11679
Type of special diet 
followed: Vegetarian || 
id:ukb-b-11679
Vigorous physical activity || id:ebi-
a-GCST006098
Simple mode
6
0.0214745
2
0.10369298
0.84410
404
ebi-a-
GCST006098
ukb-b-11679
Type of special diet 
followed: Vegetarian || 
id:ukb-b-11679
Vigorous physical activity || id:ebi-
a-GCST006098
Weighted mode
6
0.0245167
9
0.09506696
0.80677
012
ebi-a-
GCST006098
ukb-b-1996
Salad / raw vegetable 
intake || id:ukb-b-1996
Vigorous physical activity || id:ebi-
a-GCST006098
MR Egger
7
0.6661970
2
1.2339482
0.61244
007
ebi-a-
GCST006098
ukb-b-1996
Salad / raw vegetable 
intake || id:ukb-b-1996
Vigorous physical activity || id:ebi-
a-GCST006098
Weighted median
7
0.5139604
0.10299379
6.03E-
07
ebi-a-
GCST006098
ukb-b-1996
Salad / raw vegetable 
intake || id:ukb-b-1996
Vigorous physical activity || id:ebi-
a-GCST006098
Inverse variance weighted
7
0.5044851
7
0.13388668
0.00016
456
ebi-a-
GCST006098
ukb-b-1996
Salad / raw vegetable 
intake || id:ukb-b-1996
Vigorous physical activity || id:ebi-
a-GCST006098
Simple mode
7
0.6270295
4
0.14130406
0.00438
784
Table 6S. 2S-MR results with vigorous physical activity as exposure and blood biomarkers as outcomes
t lifestyle habits
S6.
S6 Table.
ebi-a-
GCST006098
ukb-b-1996
Salad / raw vegetable 
intake || id:ukb-b-1996
Vigorous physical 
activity || id:ebi-a-
GCST006098
Weighted mode
7
0.58940834
0.14675
62
0.00698
862
ebi-a-
GCST006098
ukb-b-2209
Oily fish intake || id:ukb-b-
2209
Vigorous physical 
activity || id:ebi-a-
GCST006098
MR Egger
7
0.95472369
2.00996
591
0.65481
403
ebi-a-
GCST006098
ukb-b-2209
Oily fish intake || id:ukb-b-
2209
Vigorous physical 
activity || id:ebi-a-
GCST006098
Weighted median
7
0.53975424
0.15310
124
0.00042
273
ebi-a-
GCST006098
ukb-b-2209
Oily fish intake || id:ukb-b-
2209
Vigorous physical 
activity || id:ebi-a-
GCST006098
Inverse variance weighted
7
0.48170818
0.21898
245
0.02782
414
ebi-a-
GCST006098
ukb-b-2209
Oily fish intake || id:ukb-b-
2209
Vigorous physical 
activity || id:ebi-a-
GCST006098
Simple mode
7
0.82403974
0.20581
323
0.00708
805
ebi-a-
GCST006098
ukb-b-2209
Oily fish intake || id:ukb-b-
2209
Vigorous physical 
activity || id:ebi-a-
GCST006098
Weighted mode
7
0.78663663
0.29210
032
0.03590
724
ebi-a-
GCST006098
ukb-b-3881
Fresh fruit intake || id:ukb-
b-3881
Vigorous physical 
activity || id:ebi-a-
GCST006098
MR Egger
7
1.30879467
1.11224
869
0.29227
451
ebi-a-
GCST006098
ukb-b-3881
Fresh fruit intake || id:ukb-
b-3881
Vigorous physical 
activity || id:ebi-a-
GCST006098
Weighted median
7
0.46001672
0.08901
784
2.37E-
07
ebi-a-
GCST006098
ukb-b-3881
Fresh fruit intake || id:ukb-
b-3881
Vigorous physical 
activity || id:ebi-a-
GCST006098
Inverse variance weighted
7
0.38633487
0.12863
774
0.00267
088
ebi-a-
GCST006098
ukb-b-3881
Fresh fruit intake || id:ukb-
b-3881
Vigorous physical 
activity || id:ebi-a-
GCST006098
Simple mode
7
0.59733916
0.11693
25
0.00220
313
ebi-a-
GCST006098
ukb-b-3881
Fresh fruit intake || id:ukb-
b-3881
Vigorous physical 
activity || id:ebi-a-
GCST006098
Weighted mode
7
0.58037912
0.12022
717
0.00291
812
ebi-a-
GCST006098
ukb-b-4616
Nap during day || id:ukb-b-
4616
Vigorous physical 
activity || id:ebi-a-
GCST006098
MR Egger
7
-1.8168346
0.85758
58
0.08766
702
ebi-a-
GCST006098
ukb-b-4616
Nap during day || id:ukb-b-
4616
Vigorous physical 
activity || id:ebi-a-
GCST006098
Weighted median
7
-0.3203349
0.09563
435
0.00080
934
ebi-a-
GCST006098
ukb-b-4616
Nap during day || id:ukb-b-
4616
Vigorous physical 
activity || id:ebi-a-
GCST006098
Inverse variance weighted
7
-0.1836272
0.12240
112
0.13356
03
ebi-a-
GCST006098
ukb-b-4616
Nap during day || id:ukb-b-
4616
Vigorous physical 
activity || id:ebi-a-
GCST006098
Simple mode
7
-0.3872459
0.12727
48
0.02272
693
ebi-a-
GCST006098
ukb-b-4616
Nap during day || id:ukb-b-
4616
Vigorous physical 
activity || id:ebi-a-
GCST006098
Weighted mode
7
-0.3872459
0.11249
117
0.01375
948
ebi-a-
GCST006098
ukb-b-6324
Processed meat intake || 
id:ukb-b-6324
Vigorous physical 
activity || id:ebi-a-
GCST006098
MR Egger
7
0.06859678
1.00946
468
0.94845
629
ebi-a-
GCST006098
ukb-b-6324
Processed meat intake || 
id:ukb-b-6324
Vigorous physical 
activity || id:ebi-a-
GCST006098
Weighted median
7
-0.6292381
0.13853
861
5.57E-
06
ebi-a-
GCST006098
ukb-b-6324
Processed meat intake || 
id:ukb-b-6324
Vigorous physical 
activity || id:ebi-a-
GCST006098
Inverse variance weighted
7
-0.5496216
0.11346
205
1.27E-
06
ebi-a-
GCST006098
ukb-b-6324
Processed meat intake || 
id:ukb-b-6324
Vigorous physical 
activity || id:ebi-a-
GCST006098
Simple mode
7
-0.6879646
0.21816
478
0.01972
901
ebi-a-
GCST006098
ukb-b-6324
Processed meat intake || 
id:ukb-b-6324
Vigorous physical 
activity || id:ebi-a-
GCST006098
Weighted mode
7
-0.6939066
0.21655
974
0.01850
116
id.exposure
id.outcome
outcome
exposure
Egger intercept se
pval
ebi-a-
GCST006098
ukb-b-10217
Sweets intake || id:ukb-b-
10217
Vigorous physical 
activity || id:ebi-a-
GCST006098
-0.000797
0.01392
445
0.95657
282
ebi-a-
GCST006098
ukb-b-11679
Type of special diet 
followed: Vegetarian || 
id:ukb-b-11679
Vigorous physical 
activity || id:ebi-a-
GCST006098
-0.0025594
0.00786
299
0.76112
246
ebi-a-
GCST006098
ukb-b-1996
Salad / raw vegetable intake 
|| id:ukb-b-1996
Vigorous physical 
activity || id:ebi-a-
GCST006098
-0.0015039
0.01139
436
0.90014
308
ebi-a-
GCST006098
ukb-b-2209
Oily fish intake || id:ukb-b-
2209
Vigorous physical 
activity || id:ebi-a-
GCST006098
-0.0043991
0.01856
093
0.82205
339
ebi-a-
GCST006098
ukb-b-3881
Fresh fruit intake || id:ukb-
b-3881
Vigorous physical 
activity || id:ebi-a-
GCST006098
-0.0085789
0.01027
085
0.44163
822
ebi-a-
GCST006098
ukb-b-4616
Nap during day || id:ukb-b-
4616
Vigorous physical 
activity || id:ebi-a-
GCST006098
0.01518897
0.00791
926
0.11322
178
ebi-a-
GCST006098
ukb-b-6324
Processed meat intake || 
id:ukb-b-6324
Vigorous physical 
activity || id:ebi-a-
GCST006098
-0.0057496
0.00932
2
0.56437
631
Tests for horizontal pleiotropy
id.exposure
id.outcome
outcome
exposure
method
nsn
p
b
se
pval
ukb-b-1996
ebi-a-
GCST006098
Vigorous physical activity 
|| id:ebi-a-GCST006098
Salad / raw vegetable intake || 
id:ukb-b-1996
MR Egger
2
0
0.3848011
0.33578299
0.26681
018
ukb-b-1996
ebi-a-
GCST006098
Vigorous physical activity 
|| id:ebi-a-GCST006098
Salad / raw vegetable intake || 
id:ukb-b-1996
Weighted median
2
0
0.2725700
2
0.06073408
7.19E-
06
ukb-b-1996
ebi-a-
GCST006098
Vigorous physical activity 
|| id:ebi-a-GCST006098
Salad / raw vegetable intake || 
id:ukb-b-1996
Inverse variance weighted
2
0
0.3160797
5
0.0657002
1.50E-
06
ukb-b-1996
ebi-a-
GCST006098
Vigorous physical activity 
|| id:ebi-a-GCST006098
Salad / raw vegetable intake || 
id:ukb-b-1996
Simple mode
2
0
0.3937231
5
0.14841231
0.01570
282
ukb-b-1996
ebi-a-
GCST006098
Vigorous physical activity 
|| id:ebi-a-GCST006098
Salad / raw vegetable intake || 
id:ukb-b-1996
Weighted mode
2
0
0.3979305
4
0.16695029
0.02773
826
ukb-b-6324
ebi-a-
GCST006098
Vigorous physical activity 
|| id:ebi-a-GCST006098
Processed meat intake || id:ukb-b-
6324
MR Egger
2
3
0.1350953
3
0.17451244
0.44748
219
ukb-b-6324
ebi-a-
GCST006098
Vigorous physical activity 
|| id:ebi-a-GCST006098
Processed meat intake || id:ukb-b-
6324
Weighted median
2
3
-
0.0754533
0.03693307
0.04105
493
ukb-b-6324
ebi-a-
GCST006098
Vigorous physical activity 
|| id:ebi-a-GCST006098
Processed meat intake || id:ukb-b-
6324
Inverse variance weighted
2
3
-
0.1085666
0.03736846
0.00366
899
ukb-b-6324
ebi-a-
GCST006098
Vigorous physical activity 
|| id:ebi-a-GCST006098
Processed meat intake || id:ukb-b-
6324
Simple mode
2
3
-
0.0569462
0.08563101
0.51295
016
ukb-b-6324
ebi-a-
GCST006098
Vigorous physical activity 
|| id:ebi-a-GCST006098
Processed meat intake || id:ukb-b-
6324
Weighted mode
2
3
-
0.0357803
0.07544894
0.64000
771
ukb-b-4616
ebi-a-
GCST006098
Vigorous physical activity 
|| id:ebi-a-GCST006098
Nap during day || id:ukb-b-4616
MR Egger
8
9
-
0.1310942
0.09139345
0.15504
488
ukb-b-4616
ebi-a-
GCST006098
Vigorous physical activity 
|| id:ebi-a-GCST006098
Nap during day || id:ukb-b-4616
Weighted median
8
9
-
0.0537114
0.0279262
0.05443
828
ukb-b-4616
ebi-a-
GCST006098
Vigorous physical activity 
|| id:ebi-a-GCST006098
Nap during day || id:ukb-b-4616
Inverse variance weighted
8
9
-
0.0652623
0.02490192
0.00877
309
ukb-b-4616
ebi-a-
GCST006098
Vigorous physical activity 
|| id:ebi-a-GCST006098
Nap during day || id:ukb-b-4616
Simple mode
8
9
-
0.0625663
0.0649349
0.33792
525
ukb-b-4616
ebi-a-
GCST006098
Vigorous physical activity 
|| id:ebi-a-GCST006098
Nap during day || id:ukb-b-4616
Weighted mode
8
9
-
0.0482764
0.05502095
0.38264
819
ukb-b-3881
ebi-a-
GCST006098
Vigorous physical activity 
|| id:ebi-a-GCST006098
Fresh fruit intake || id:ukb-b-3881
MR Egger
5
3
-
0.0277245
0.12616196
0.82694
037
Table 7S. 2S-MR with healthy/unhealthy dietary habits as exposures and vigorous physical activity as outcome to assess 
reverse causality
S7 Table.
ukb-b-3881
ebi-a-
GCST006098
Vigorous physical activity || 
id:ebi-a-GCST006098
Fresh fruit intake || 
id:ukb-b-3881
Weighted median
53
0.16136177
0.03846
63
2.73E-
05
ukb-b-3881
ebi-a-
GCST006098
Vigorous physical activity || 
id:ebi-a-GCST006098
Fresh fruit intake || 
id:ukb-b-3881
Inverse variance weighted
53
0.2103584
0.03697
867
1.28E-
08
ukb-b-3881
ebi-a-
GCST006098
Vigorous physical activity || 
id:ebi-a-GCST006098
Fresh fruit intake || 
id:ukb-b-3881
Simple mode
53
0.16760638
0.09363
947
0.07929
148
ukb-b-3881
ebi-a-
GCST006098
Vigorous physical activity || 
id:ebi-a-GCST006098
Fresh fruit intake || 
id:ukb-b-3881
Weighted mode
53
0.14738639
0.08743
063
0.09783
589
id.exposure
id.outcome
outcome
exposure
Egger intercept se
pval
ukb-b-1996
ebi-a-
GCST006098
Vigorous physical activity || 
id:ebi-a-GCST006098
Salad / raw vegetable 
intake || id:ukb-b-
1996
-0.0007564
0.00362
056
0.83686
113
ukb-b-6324
ebi-a-
GCST006098
Vigorous physical activity || 
id:ebi-a-GCST006098
Processed meat 
intake || id:ukb-b-
6324
-0.0037415
0.00262
036
0.16803
755
ukb-b-4616
ebi-a-
GCST006098
Vigorous physical activity || 
id:ebi-a-GCST006098
Nap during day || 
id:ukb-b-4616
0.00064846
0.00086
601
0.45600
425
ukb-b-3881
ebi-a-
GCST006098
Vigorous physical activity || 
id:ebi-a-GCST006098
Fresh fruit intake || 
id:ukb-b-3881
0.00227091
0.00115
335
0.05440
223
Tests for horizontal pleiotropy
Figure 1S.  Assumptions of Mendelian randomization: (1)  the genetic instrument is associated with 
the exposure. (2) the genetic instrument should not associate with a confounder. (3) the genetic 
instrument should affect the outcome only via the exposure.
S1 Fig. 
Figure 2S.  Blood biomarker levels with respect to self-reported running volume and professional 
athletes in males (m) and females (f).
Fig. S2.
S2 Fig. 
Figure 3S. 2S-MR scatter plot showing effects of vigorous physical activity as the exposure on (A) 
SHBG (B) Red blood cell count (C) Folate (D) Triglycerides (E) Ferritin (F) LDL as outcomes (see Table 
5S for statistical significance). 
A
B
C
D
E
F
Fig. S3.
S3 Fig. 
Figure 4S. 2S-MR scatter plot showing effects of vigorous physical activity as the exposure on (A) oily
fish consumption (B) salad intake(C) fresh fruit intake (D) processed meat intake (E) daytime 
napping (F) sweets intake (G) vegetarian diet (see Table 6S for statistical significance). 
E
F
G
Fig. S4.
S4 Fig. 
Figure 5S. 2S-MR scatter plot showing effects of dietary behaviors as the exposures on vigorous 
physical activity: (A) salad intake (B) processed meat intake (C) daytime napping (D) fresh fruit intake 
(see Table 7S for statistical significance).
A
B
C
D
S5 Fig. 

Dose response of running on blood biomarkers of wellness in generally healthy individuals.
Nogal, Bartek,Vinogradova, Svetlana,Jorge, Milena,Torkamani, Ali,Fabian, Paul,Blander, Gil