Risteys · E4_FLUIDOVER

Endpoint definition steps	FinnGen
Phenotype data	520210
1. Apply sex-specific rule None	520210
2. Check conditions None	520210
3. Check pre-conditions, main-only, mode, registry filters Registry filters: Hospital discharge: ICD-10 — E87.7 Cause of death: ICD-10 — E87.7 2 out of 7 registries used, show all original rules.	98
4. Check minimum number of events None	98
5. Include endpoints None	98
6. Filter based on genotype QC (FinnGen only)	98

Summary Statistics

↥

-FinRegistry-

Key figures

	All	Female	Male
Number of individuals
Whole population	582	293	287
Only index persons	524	263	261
Unadjusted period prevalence (%)
Whole population	0.01	0.01	0.01
Only index persons	0.01	0.01	0.01
Median age at first event (years)
Whole population	69.82	72.88	66.78
Only index persons	69.84	72.88	66.78

-FinnGen-

Key figures

	All	Female	Male
Number of individuals	98	46	52
Unadjusted period prevalence (%)	0.02	0.02	0.02
Median age at first event (years)	63.74	68.23	59.78

-FinRegistry-

Age distribution of first events

-FinnGen-

Age distribution of first events

-FinRegistry-

Year distribution of first events

-FinnGen-

Year distribution of first events

-FinRegistry-

Cumulative Incidence Function

-FinnGen-

Cumulative Incidence Function

No data

CodeWAS (R11)

↥

CodeWAS is a tool for exploring the associations between an endpoint and all of the medical codes and drug codes.

This is a new tool, please reach out using the contact form for feedback and improvement ideas.

First, a cohort is built by matching controls to the endpoint cases using year of birth and sex. Then, a Fisher test is done for all the medical codes and drug codes between the cases and controls of this cohort. Codes are reported in the table below if they have −log₁₀(p-value) ≥ 6.

Matched cohort

Matched cases
88: Matched controls
879

Code

Vocabulary

Description

Odds Ratio

-log₁₀(p)

N matched cases

N matched controls

E87.7

ICD-10 Finland

Fluid overload

+∞

126.7

Z49.1

ICD-10 Finland

Extracorporeal dialysis

247.0

33.2

N18.9

ICD-10 Finland

Chronic kidney disease, unspecified

35.2

32.1

C03CA01

ATC

furosemide; systemic

17.6

31.0

159

TK800

NOMESCO Finland

Hemodialysis

117.4

30.1

138

Kela drug reimbursment

Severe anaemia associated with chronic renal failure

73.8

30.0

123

Kela drug reimbursment

Chronic disorders of vitamin D metabolism

55.7

26.0

I50.9

ICD-10 Finland

Heart failure, unspecified

14.4

24.1

PBL10

NOMESCO Finland

Construction of arteriovenous fistula from radial artery

162.5

23.9

N18.8

ICD-10 Finland

Other chronic renal failure

37.0

23.8

E87.1

ICD-10 Finland

Hypo-osmolality and hyponatraemia

+∞

21.8

190

Kela drug reimbursment

Lanthanum carbonate, sevelamer and sucroferric oxyhydroxide

136.0

20.6

FM1EE

NOMESCO Finland

Extensive structural and functional ultrasound examination of heart

9.8

20.2

104

GD1UA

NOMESCO Finland

Thorax X-ray examination outside radiological department

10.9

19.1

TPX10

NOMESCO Finland

Implantation of vascular injection port

85.0

18.6

GD1AA

NOMESCO Finland

Thorax X-ray examination

8.7

18.3

271

A12AA04

ATC

calcium carbonate; oral

54.2

18.2

N18.0

ICD-10 Finland

End-stage renal disease

+∞

17.2

OAB74

NOMESCO Finland

Nutritional guidance related to treatment and rehabilitation for medical condition

207.8

17.1

A10AC01

ATC

insulin (human); parenteral (insulins and analog. for injection, intermediate-acting)

17.1

16.8

B03XA02

ATC

darbepoetin alfa; parenteral

30.1

16.0

Z71.3

ICD-10 Finland

Dietary counselling and surveillance

18.9

15.7

J18.9

ICD-10 Finland

Pneumonia, unspecified

7.0

15.3

123

JN3AE

NOMESCO Finland

Abdominal ultrasound examination

8.8

15.2

I15.1

ICD-10 Finland

Hypertension secondary to other renal disorders

51.8

14.7

N17.9

ICD-10 Finland

Acute renal failure, unspecified

23.0

14.2

A10AB05

ATC

insulin aspart; parenteral (insulins and analog. for injection, fast-acting)

14.5

14.1

A10AE04

ATC

insulin glargine; parenteral

10.9

14.0

E10.7

ICD-10 Finland

Type 1 diabetes mellitus, With multiple complications

48.1

13.7

PH2AE

NOMESCO Finland

Ultrasound examination of lower leg veins

9.8

13.6

A11CC03

ATC

alfacalcidol; systemic

27.8

13.5

TPH15

NOMESCO Finland

Insertion of central venous catheter through external or internal jugular vein

14.4

13.5

SPAT1262

SPAT

Handing over of treatment supplies

7.0

13.4

TPH90

NOMESCO Finland

Removal of fixed intravenous catheter

59.5

13.3

E11.2

ICD-10 Finland

Type 2 diabetes mellitus, with renal complications

59.5

13.3

E11.7

ICD-10 Finland

Type 2 diabetes mellitus, with multiple complications

16.8

13.3

A49.9

ICD-10 Finland

Bacterial infection, unspecified

8.3

13.0

E87.5

ICD-10 Finland

Hyperkalaemia

+∞

12.8

320

Kela drug reimbursment

Lanthanum carbonate, sevelamer and sucroferric oxyhydroxide

150.6

12.8

ZXM10

NOMESCO Finland

Intraoperative use of conventional X-ray imaging

18.2

12.5

SPAT1148

SPAT

Treatment of chronic ulcer or burn

7.3

12.4

215

Kela drug reimbursment

Diabetes, non-insulin-treated

5.8

12.4

130

103

Kela drug reimbursment

Diabetes, insulin-treated

5.5

12.2

146

N19

ICD-10 Finland

Unspecified kidney failure

24.0

11.6

NH3AA

NOMESCO Finland

Foot and toes X-ray examination

10.0

11.3

TPH20

NOMESCO Finland

Insertion of central venous catheter through subclavian or brachiocephalic vein

32.8

11.1

GD1QA

NOMESCO Finland

Supine thorax X-ray examination

6.2

11.1

A46

ICD-10 Finland

Erysipelas

6.8

11.0

M04AA01

ATC

allopurinol; systemic

6.6

11.0

C07AB07

ATC

bisoprolol; oral

4.9

11.0

308

XF600

NOMESCO Finland

Bloodpressure measurement

10.1

11.0

M10.9

ICD-10 Finland

Gout, unspecified

11.4

10.7

N08.39*E10.2

ICD-10 Finland

Insulin-dependent diabetes mellitus - Diabetic nephropathy

124.2

10.7

V03AE01

ATC

polystyrene sulfonate; oral

124.2

10.7

XPX99

NOMESCO Finland

Other diagnostic examination of periferal vessel

12.4

10.7

PH1AE

NOMESCO Finland

Ultrasound examination of upper extremity veins

30.1

10.1

A10AE05

ATC

insulin detemir; parenteral

13.7

10.1

L97

ICD-10 Finland

Ulcer of lower limb, not elsewhere classified

17.8

9.9

L04AD02

ATC

tacrolimus; systemic (calcineurin inhibitors)

62.1

9.9

137

Kela drug reimbursment

Uraemia requiring dialysis

62.1

9.9

Z94.0

ICD-10 Finland

Kidney transplant status

62.1

9.9

GD1PA

NOMESCO Finland

X-ray examination of the lungs in one projection

8.3

9.8

I50.0

ICD-10 Finland

Congestive heart failure

8.3

9.8

ZXD05

NOMESCO Finland

Urgent procedure

4.5

9.7

173

E11.9

ICD-10 Finland

Type 2 diabetes mellitus, without complications

4.9

9.7

113

L04AA06

ATC

mycophenolic acid; systemic

34.3

9.7

S97

ICPC

Chronic ulcer skin

11.0

9.6

J01FF01

ATC

clindamycin; systemic

4.6

9.5

141

D64.9

ICD-10 Finland

Anaemia, unspecified

7.1

9.5

B01AB10

ATC

tinzaparin; parenteral

10.5

9.4

R50.9

ICD-10 Finland

Fever, unspecified

5.3

9.3

C08CA01

ATC

amlodipine; oral

4.2

9.3

208

Z49.2

ICD-10 Finland

Other dialysis

41.4

9.3

WX204

NOMESCO Finland

Axillary plexus blockaced

12.7

9.2

R06.0

ICD-10 Finland

Dyspnoea

4.4

9.1

146

A10AA02

ATC

16.3

9.0

A10AB01

ATC

insulin (human); parenteral (insulins and analog. for injection, fast-acting)

16.3

9.0

FN1AC

NOMESCO Finland

Angiography of heart and/or coronary arteries

4.9

8.9

NA3AA

NOMESCO Finland

Lumbar spine X-ray examination without contrast

7.2

8.9

KAS10

NOMESCO Finland

Allogenic transplantation of kidney from cadaver donor

55.7

8.9

A10AA01

ATC

22.8

8.7

H04AA01

ATC

glucagon; nasal, parenteral

31.0

8.7

127

Kela drug reimbursment

Transplant complication

31.0

8.7

E10.2

ICD-10 Finland

Type 1 diabetes mellitus, With renal complications

99.2

8.6

V03AE02

ATC

sevelamer; oral

99.2

8.6

JAK10

NOMESCO Finland

Laparotomy and insertion of peritoneal dialysis catheter

99.2

8.6

ZXE00

NOMESCO Finland

One hour or less

3.9

8.6

221

A10BH05

ATC

linagliptin; oral

16.7

8.5

V03AE03

ATC

lanthanum carbonate; oral

+∞

8.5

N08.39*E11.2

ICD-10 Finland

Non-insulin-dependent diabetes mellitus - Diabetic nephropathy

37.1

8.3

PG1DE

NOMESCO Finland

Other extensive ultrasound examination of artery

24.8

8.2

A12AX

ATC

Calcium, combinations with vitamin D and/or other drugs

3.9

8.2

187

I25.1

ICD-10 Finland

Atherosclerotic heart disease

4.5

8.2

NH1AA

NOMESCO Finland

Ankle X-ray examination without contrast

8.9

8.1

PA6DE

NOMESCO Finland

Neck artery ultrasound examination with Doppler method

12.5

8.1

I70.2

ICD-10 Finland

Atherosclerosis of arteries of extremities

7.5

8.1

ZXE10

NOMESCO Finland

More than one and less than three hours

3.8

8.0

197

E11.8

ICD-10 Finland

Type 2 diabetes mellitus, with unspecified complications

6.9

8.0

UJD10

NOMESCO Finland

Esophagoscopy, gastroscopy and duodenoscopy

3.9

8.0

161

DM1QA

NOMESCO Finland

Paranasal sinuses X-ray examination in one projection

10.4

7.9

H02AB06

ATC

prednisolone; systemic

3.7

7.9

282

X59

ICD-10 Finland

Exposure to unspecified factor

4.4

7.8

QXB99

NOMESCO Finland

Other procedure to treat skin wound, unspecified location

27.8

7.8

TPH07

NOMESCO Finland

Cathetrisation of artery

5.9

7.7

WX892

NOMESCO Finland

Monitored bed care

6.8

7.6

EBA15

NOMESCO Finland

Extraction of large number of teeth

10.9

7.6

NHQ40

NOMESCO Finland

Amputation of toe

87.1

7.5

KA9AE

NOMESCO Finland

Ultrasound examination transplanted kidney

+∞

7.4

H05BX01

ATC

cinacalcet; oral

+∞

7.4

196

Kela drug reimbursment

Paricalcitol and cinacalcet

+∞

7.4

B03XA03

ATC

methoxy polyethylene glycol-epoetin beta; parenteral

+∞

7.4

WX408

NOMESCO Finland

General anesthesy, balanced

3.8

7.2

142

WW500

NOMESCO Finland

Blood transfusion

9.6

7.1

E78.5

ICD-10 Finland

Hyperlipidaemia, unspecified

15.5

7.1

I48.0

ICD-10 Finland

Paroxysmal atrial fibrillation

12.4

7.0

J01MA12

ATC

levofloxacin; systemic

4.0

7.0

111

H3603, E103

ICD-10 Finland

43.5

6.9

B05DB

ATC

Hypertonic solutions

43.5

6.9

B05DA

ATC

Isotonic solutions

43.5

6.9

JN4AD

NOMESCO Finland

Body CT examination

7.3

6.9

J20.9

ICD-10 Finland

Acute bronchitis, unspecified

4.2

6.8

T89

ICPC

Diabetes insulin dependent

11.4

6.8

C03DA01

ATC

spironolactone; oral

5.2

6.7

J01MA14

ATC

moxifloxacin; systemic

5.4

6.7

WYA30

NOMESCO Finland

Preparations for expected poor cooperation

7.0

6.7

A10AD01

ATC

insulin (human); parenteral (insulins and analog. for injection, intermediate- or long-acting comb. with fast-acting)

15.9

6.6

Z2446

NOMESCO Finland

Social worker

8.1

6.5

E10.8

ICD-10 Finland

Type 1 diabetes mellitus, With unspecified complications

75.1

6.5

E86

ICD-10 Finland

Volume depletion

75.1

6.5

OAB73

NOMESCO Finland

Prevention and treatment of malnutrition

75.1

6.5

E10.1

ICD-10 Finland

Type 1 diabetes mellitus, With ketoacidosis

75.1

6.5

A02BC02

ATC

pantoprazole; systemic

3.5

6.5

433

E10.9

ICD-10 Finland

Type 1 diabetes mellitus, Without complications

12.4

6.5

R60.9

ICD-10 Finland

Oedema, unspecified

12.4

6.5

T90

ICPC

Diabetes non-insulin dependent

3.7

6.5

123

L03.1

ICD-10 Finland

Cellulitis of other parts of limb

19.8

6.4

JN1AE

NOMESCO Finland

Ultrasound examination of upper part of abdomen

5.7

6.4

N10

ICD-10 Finland

Acute tubulo-interstitial nephritis

4.5

6.4

N18.5

ICD-10 Finland

Chronic kidney disease, stage 5

+∞

6.3

QXA20

NOMESCO Finland

Skin abrasion, unspecified location

+∞

6.3

WX213

NOMESCO Finland

Lower leg blockade

+∞

6.3

N25.8

ICD-10 Finland

Other disorders resulting from impaired renal tubular function

+∞

6.3

M10.3

ICD-10 Finland

Gout due to impairment of renal function

+∞

6.3

PB1AC

NOMESCO Finland

Angiography of upper extremity with X-ray

+∞

6.3

ZX108

NOMESCO Finland

Inhalation

+∞

6.3

KA2AT

NOMESCO Finland

Biopsy of transplanted kidney with ultrasound guidance

+∞

6.3

206

Kela drug reimbursment

Chronic coronary artery disease and dyslipidaemia associated with chronic coronary artery disease

4.2

6.3

A41.9

ICD-10 Finland

Sepsis, unspecified

13.9

6.3

R4110

NOMESCO Finland

Physiotherapy

3.5

6.2

141

SPAT1255

SPAT

Intravenous administration of medicine

8.3

6.2

B01AA03

ATC

warfarin; systemic

3.7

6.2

109

C09AA02

ATC

enalapril; systemic

3.9

6.1

SPAT1222

SPAT

Counselling/guidance promoting independent living

3.9

6.1

JN3AD

NOMESCO Finland

Abdominal CT examination

6.1

I50.1

ICD-10 Finland

Left ventricular failure

9.1

6.1

WX002

NOMESCO Finland

Sedation and analgesia

3.8

6.1

C07AB02

ATC

metoprolol; systemic

3.7

6.0

104

A41.0

ICD-10 Finland

Sepsis due to Staphylococcus aureus

16.5

6.0

Mortality – FinRegistry

↥

Association

Association between endpoint E4_FLUIDOVER and mortality.

Females

Parameter	HR [95% CI]	p-value
E4_FLUIDOVER	3.281 [1.98, 5.44]	< 0.001
Birth year	0.993 [0.98, 1.0]	0.135

During the follow-up period (1.1.1998 — 31.12.2019), 103 out of 212 females with E4_FLUIDOVER died.

Males

Parameter	HR [95% CI]	p-value
E4_FLUIDOVER	6.861 [3.77, 12.48]	< 0.001
Birth year	0.992 [0.98, 1.0]	0.098

During the follow-up period (1.1.1998 — 31.12.2019), 127 out of 212 males with E4_FLUIDOVER died.

Mortality risk

Mortality risk for people of age

years, who have E4_FLUIDOVER.

N-year risk	Females	Males
1	0.229%	1.763%
5	1.508%	9.368%
10	4.476%	22.161%
15	8.006%	39.888%
20	13.834%	56.64%

Relationships between endpoints

↥

Index endpoint: E4_FLUIDOVER – Fluid overload

GWS hits: -

Endpoint

Case Overlap

Survival Analysis

Genetic Correlations

Genetic Signals

N (Jaccard index)

HR [CI]

Extremity

rg [CI]

Extremity

Hits

Coloc Hits

FinRegistry

FinnGen

FinRegistry

FinnGen

Loading data

NAME	E4_FLUIDOVER
CONTROL_EXCLUDE	E4_METABOLIA
CONTROL_PRECONDITIONS
CONTROL_CONDITIONS
SEX
INCLUDE
PRE_CONDITIONS
CONDITIONS
OUTPAT_ICD
OUTPAT_OPER
HD_MAINONLY
HD_ICD_10_ATC
HD_ICD_10	E877
HD_ICD_9	$!$	The FinnGen clinical team has checked and no code can be used for this rule.
HD_ICD_8	$!$	The FinnGen clinical team has checked and no code can be used for this rule.
HD_ICD_10_EXCL
HD_ICD_9_EXCL
HD_ICD_8_EXCL
COD_MAINONLY
COD_ICD_10	E877
COD_ICD_9	$!$	The FinnGen clinical team has checked and no code can be used for this rule.
COD_ICD_8	$!$	The FinnGen clinical team has checked and no code can be used for this rule.
COD_ICD_10_EXCL
COD_ICD_9_EXCL
COD_ICD_8_EXCL
OPER_NOM
OPER_HL
OPER_HP1
OPER_HP2
KELA_REIMB
KELA_REIMB_ICD
KELA_ATC_NEEDOTHER
KELA_ATC
KELA_VNRO_NEEDOTHER
KELA_VNRO
CANC_TOPO
CANC_TOPO_EXCL
CANC_MORPH
CANC_MORPH_EXCL
CANC_BEHAV

Fluid overload

Endpoint definition

Endpoint definition steps

FinnGen

Phenotype data

1. Apply sex-specific rule

2. Check conditions

3. Check pre-conditions, main-only, mode, registry filters

4. Check minimum number of events

5. Include endpoints

6. Filter based on genotype QC (FinnGen only)

Similar endpoints

Case counts by codes

Summary Statistics

-FinRegistry-

Key figures

-FinnGen-

Key figures

-FinRegistry-

Age distribution of first events

-FinnGen-

Age distribution of first events

-FinRegistry-

Year distribution of first events

-FinnGen-

Year distribution of first events

-FinRegistry-

Cumulative Incidence Function

-FinnGen-

Cumulative Incidence Function

CodeWAS (R11)

Matched cohort

Mortality – FinRegistry

Association

Females

Males

Mortality risk

Relationships between endpoints