Risteys · K11

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 — K71 Cause of death: ICD-10 — K71 2 out of 7 registries used, show all original rules.	541
4. Check minimum number of events None	541
5. Include endpoints None	541
6. Filter based on genotype QC (FinnGen only)	541

Summary Statistics

↥

-FinRegistry-

Key figures

	All	Female	Male
Number of individuals
Whole population	3897	2092	1772
Only index persons	3296	1812	1484
Unadjusted period prevalence (%)
Whole population	0.05	0.06	0.05
Only index persons	0.06	0.07	0.06
Median age at first event (years)
Whole population	56.47	57.86	54.71
Only index persons	55.21	56.21	53.98

-FinnGen-

Key figures

	All	Female	Male
Number of individuals	541	314	227
Unadjusted period prevalence (%)	0.10	0.11	0.10
Median age at first event (years)	54.98	54.18	56.09

-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)

↥

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
483: Matched controls
4832

Code

Vocabulary

Description

Odds Ratio

-log₁₀(p)

N matched cases

N matched controls

K71.2

ICD-10 Finland

Toxic liver disease with acute hepatitis

+∞

244.1

213

K71.9

ICD-10 Finland

Toxic liver disease, unspecified

1660.4

134.0

124

K71.0

ICD-10 Finland

Toxic liver disease with cholestasis

+∞

76.1

K75.9

ICD-10 Finland

Inflammatory liver disease, unspecified

+∞

75.0

JJ2AT

NOMESCO Finland

Biopsy of liver with ultrasound guidance

59.8

65.4

K76.9

ICD-10 Finland

Liver disease, unspecified

206.3

54.2

R17

ICD-10 Finland

Hyperbilirubinaemia, with or without jaundice, not elsewhere classified

44.2

50.5

JN1AE

NOMESCO Finland

Ultrasound examination of upper part of abdomen

6.9

39.9

108

193

JN3AE

NOMESCO Finland

Abdominal ultrasound examination

5.5

39.9

134

316

A05AA02

ATC

ursodeoxycholic acid; oral

41.7

39.6

R74.0

ICD-10 Finland

Elevation of levels of transaminase and lactic acid dehydrogenase [LDH]

32.2

39.6

K71.1

ICD-10 Finland

Toxic liver disease with hepatic necrosis

+∞

39.1

K72.0

ICD-10 Finland

Acute and subacute hepatic failure

+∞

28.4

K70.1

ICD-10 Finland

Alcoholic hepatitis

+∞

26.3

L04AX01

ATC

azathioprine; systemic

8.9

25.2

K71.6

ICD-10 Finland

Toxic liver disease with hepatitis, not elsewhere classified

+∞

24.2

K74.6

ICD-10 Finland

Other and unspecified cirrhosis of liver

+∞

22.0

K73.2

ICD-10 Finland

Chronic active hepatitis, not elsewhere classified

+∞

19.9

K72.9

ICD-10 Finland

Hepatic failure, unspecified

+∞

19.9

202

Kela drug reimbursment

Connective tissue diseases, rheumatoid arthritis and comparable disease

3.7

19.1

279

N05CF01

ATC

zopiclone; oral

2.5

18.2

193

1018

UJD10

NOMESCO Finland

Esophagoscopy, gastroscopy and duodenoscopy

2.5

17.6

171

859

JN1CG

NOMESCO Finland

Extensive MRI examination of upper part of abdomen with high intensity magnet

9.4

17.5

GD1AA

NOMESCO Finland

Thorax X-ray examination

2.3

17.4

237

1409

K71.3

ICD-10 Finland

Toxic liver disease with chronic persistent hepatitis

+∞

15.7

JJ1LE

NOMESCO Finland

Ultrasound elastography of liver

29.7

15.3

L04AA06

ATC

mycophenolic acid; systemic

12.4

15.2

K73.9

ICD-10 Finland

Chronic hepatitis, unspecified

+∞

14.7

K74.3

ICD-10 Finland

Primary biliary cirrhosis

+∞

14.7

JN3DE

NOMESCO Finland

Abdominal extensive ultrasoudn examination with blood flow measurements after transplantation

37.3

14.5

TPH04

NOMESCO Finland

Cathetrisation of vein

2.6

14.4

123

564

H02AB06

ATC

prednisolone; systemic

2.1

14.3

250

1616

N05AH04

ATC

quetiapine; oral

2.8

14.3

105

442

T36

ICD-10 Finland

Poisoning by systemic antibiotics

4.8

14.0

106

ZX120

NOMESCO Finland

Intravenous

3.3

13.5

244

GD1UA

NOMESCO Finland

Thorax X-ray examination outside radiological department

2.8

13.3

386

WX892

NOMESCO Finland

Monitored bed care

3.7

12.5

160

A12AX

ATC

Calcium, combinations with vitamin D and/or other drugs

2.2

12.5

170

973

A06AD11

ATC

lactulose; oral

2.7

12.4

378

R94.5

ICD-10 Finland

Abnormal results of liver function studies

12.9

12.2

Z94.4

ICD-10 Finland

Liver transplant status

47.9

11.9

X69

ICD-10 Finland

Intentional self-poisoning by and exposure to other and unspecified chemicals and noxious substances

5.2

11.7

N05CD07

ATC

temazepam; oral

2.9

11.6

283

JJ9AE

NOMESCO Finland

Ultrasound examination of liver transplant

+∞

11.5

I85.9

ICD-10 Finland

Oesophageal varices without bleeding

+∞

11.5

JJC00

NOMESCO Finland

Allogenic transplantation of liver

+∞

11.5

K70.3

ICD-10 Finland

Alcoholic cirrhosis of liver

122.8

11.5

N07BB01

ATC

disulfiram; oral

4.5

11.4

D97

ICPC

Liver disease NOS

44.4

11.0

H02AB04

ATC

methylprednisolone; systemic

2.6

11.0

372

R50.9

ICD-10 Finland

Fever, unspecified

2.6

10.9

360

JN3CD

NOMESCO Finland

Abdominal CT examination both without and with contrast

5.9

10.9

N06AX11

ATC

mirtazapine; oral

2.0

10.7

169

1013

K83.0

ICD-10 Finland

Cholangitis

13.3

10.7

N02AX02

ATC

tramadol; systemic, rectal

1.9

10.6

218

1446

K75.2

ICD-10 Finland

Nonspecific reactive hepatitis

+∞

10.5

N17.9

ICD-10 Finland

Acute renal failure, unspecified

4.8

10.4

JKE98

NOMESCO Finland

Other transduodenal endoscopic operation on bile duct or ampulla of Vater

9.9

10.3

C10AC01

ATC

colestyramine; oral

5.6

10.3

F10.1

ICD-10 Finland

Mental and behavioural disorders due to use of alcohol, Harmful use

3.4

10.2

154

A02BC02

ATC

pantoprazole; systemic

1.9

10.2

317

2421

UJF32

NOMESCO Finland

Coloscopy

2.1

10.0

134

750

N05BA04

ATC

oxazepam; oral

2.1

10.0

135

758

K76.0

ICD-10 Finland

Fatty (change of) liver, not elsewhere classified

17.2

9.9

F32.9

ICD-10 Finland

Depressive episode, unspecified

2.7

9.8

292

XF400

NOMESCO Finland

ECG with 12 standard connections

2.4

9.8

428

A07EA06

ATC

budesonide; oral, local oral

5.1

9.8

127

Kela drug reimbursment

Transplant complication

9.4

9.6

N05BA01

ATC

diazepam; systemic, rectal

2.5

9.5

366

L04AD01

ATC

ciclosporin; systemic

7.8

9.5

Z3231

NOMESCO Finland

Registered nurse

2.0

9.4

143

837

K75.4

ICD-10 Finland

Autoimmune hepatitis

+∞

9.4

C03DA01

ATC

spironolactone; oral

2.8

9.4

235

JL5BG

NOMESCO Finland

MRI examinaiton of bile and pancreas ducts with high intesity magnet

6.3

9.3

N05AH03

ATC

olanzapine; systemic

3.6

9.3

126

ZXD05

NOMESCO Finland

Urgent procedure

1.9

9.3

157

957

A49.9

ICD-10 Finland

Bacterial infection, unspecified

2.7

9.2

257

112

Kela drug reimbursment

Severe psychotic and other severe mental disorders

3.0

8.8

177

H02AB07

ATC

prednisone; oral

2.4

8.6

363

L04AX03

ATC

methotrexate; systemic (immunosuppressants)

2.8

8.6

223

TNX10

NOMESCO Finland

Arthrocentesis, unspecified region, unspecified region

3.1

8.5

153

K70.0

ICD-10 Finland

Alcoholic fatty liver

91.6

8.4

F10.21

ICD-10 Finland

Alcohol dependence currently abstinent, but staying in restrictive environment

13.1

8.4

R10.4

ICD-10 Finland

Other and unspecified abdominal pain

1.8

8.4

177

1158

K71.8

ICD-10 Finland

Toxic liver disease with other disorders of liver

+∞

8.4

K70.9

ICD-10 Finland

Alcoholic liver disease, unspecified

+∞

8.4

ZXE20

NOMESCO Finland

More than three and less than five hours

2.4

8.2

327

K85

ICD-10 Finland

Acute pancreatitis

7.7

8.2

UJK02

NOMESCO Finland

ERCP

6.0

8.1

TPH15

NOMESCO Finland

Insertion of central venous catheter through external or internal jugular vein

3.3

8.1

124

J18.9

ICD-10 Finland

Pneumonia, unspecified

2.0

8.0

118

675

C03CA01

ATC

furosemide; systemic

1.9

8.0

136

824

N06AX12

ATC

bupropion; oral

3.4

8.0

119

R53

ICD-10 Finland

Malaise and fatigue

2.0

7.9

110

617

ZXE00

NOMESCO Finland

One hour or less

1.8

7.8

189

1287

ND2AA

NOMESCO Finland

Hand and fingers X-ray examination

2.7

7.4

205

N06AB04

ATC

citalopram; systemic

2.0

7.4

108

616

K71.4

ICD-10 Finland

Toxic liver disease with chronic lobular hepatitis

+∞

7.3

K71.7

ICD-10 Finland

Toxic liver disease with fibrosis and cirrhosis of liver

+∞

7.3

JJ5AT

NOMESCO Finland

+∞

7.3

N03AX16

ATC

pregabalin; oral

1.9

7.3

119

705

L04AA01

ATC

[U] ciclosporin; systemic

7.5

7.2

WX700

NOMESCO Finland

Respiratory and circulatory monitoring

2.1

7.2

444

J01MA02

ATC

ciprofloxacin; systemic

1.7

7.2

178

1211

TK800

NOMESCO Finland

Hemodialysis

5.2

7.2

AA1AD

NOMESCO Finland

CT of head and brain

1.9

7.1

113

664

J01MA12

ATC

levofloxacin; systemic

2.0

7.1

502

F29

ICD-10 Finland

Unspecified nonorganic psychosis

3.9

7.0

ZY010

NOMESCO Finland

Hospital outpatient

3.4

6.8

100

M05BA04

ATC

alendronic acid; oral

2.7

6.8

170

K83.1

ICD-10 Finland

Obstruction of bile duct

9.5

6.8

JN1DG

NOMESCO Finland

Very extensive MRI examination of upper part of abdomen with high intensity magnet

5.8

6.8

C07AA05

ATC

propranolol; systemic

1.9

6.8

564

F10.29

ICD-10 Finland

Addiction caused by alcohol UNS

4.8

6.8

TJJ00

NOMESCO Finland

Percutaneous needle biopsy of liver

40.6

6.8

A02BC05

ATC

esomeprazole; systemic

1.7

6.7

190

1342

N05AX12

ATC

aripiprazole; systemic

3.7

6.6

K92.0

ICD-10 Finland

Haematemesis

5.5

6.5

N03AE01

ATC

clonazepam; systemic

3.1

6.5

116

A07EC02

ATC

mesalazine; oral, rectal

3.1

6.5

116

GD1QA

NOMESCO Finland

Supine thorax X-ray examination

2.1

6.5

381

K76.89

ICD-10 Finland

Other specified diseases of liver

70.7

6.4

R56.8

ICD-10 Finland

Other and unspecified convulsions

3.4

6.4

JL5AG

NOMESCO Finland

Simple MRI examinaiton of bile and pancreas ducts with high intesity magnet

9.4

6.3

N02AE01

ATC

buprenorphine; parenteral, sublingual, transdermal

2.2

6.3

294

JN3BD

NOMESCO Finland

Extensive abdominal CT

2.3

6.3

259

K71.5

ICD-10 Finland

Toxic liver disease with chronic active hepatitis

+∞

6.3

K72.1

ICD-10 Finland

Chronic hepatic failure

+∞

6.3

N10

ICD-10 Finland

Acute tubulo-interstitial nephritis

2.2

6.2

301

R4110

NOMESCO Finland

Physiotherapy

1.8

6.2

133

858

F32.2

ICD-10 Finland

Severe depressive episode without psychotic symptoms

3.0

6.2

123

F05.9

ICD-10 Finland

Delirium, unspecified

5.9

6.2

P76

ICPC

Depressive disorder

3.0

6.2

124

L88

ICPC

Rheumatoid/seropositive arthritis

3.8

6.2

P01BA02

ATC

hydroxychloroquine; oral

2.5

6.2

193

L04AA13

ATC

leflunomide; oral

4.5

6.1

X44

ICD-10 Finland

Accidental poisoning by and exposure to other and unspecified drugs, medicaments and biological substances

5.7

6.0

WX882

NOMESCO Finland

High dependency care

4.7

6.0

Z2446

NOMESCO Finland

Social worker

2.8

6.0

134

Mortality – FinRegistry

↥

Association

Association between endpoint K11_TOXLIV and mortality.

Females

Parameter	HR [95% CI]	p-value
K11_TOXLIV	2.305 [1.95, 2.72]	< 0.001
Birth year	0.995 [0.99, 1.0]	0.287

During the follow-up period (1.1.1998 — 31.12.2019), 482 out of 1710 females with K11_TOXLIV died.

Males

Parameter	HR [95% CI]	p-value
K11_TOXLIV	3.07 [2.52, 3.74]	< 0.001
Birth year	0.99 [0.98, 1.0]	0.036

During the follow-up period (1.1.1998 — 31.12.2019), 519 out of 1402 males with K11_TOXLIV died.

Mortality risk

Mortality risk for people of age

years, who have K11_TOXLIV.

N-year risk	Females	Males
1	0.296%	0.643%
5	1.451%	3.723%
10	3.399%	8.851%
15	6.4%	17.475%
20	11.149%	28.193%

Relationships between endpoints

↥

Index endpoint: K11_TOXLIV – Toxic liver disease

GWS hits: 1

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	K11_TOXLIV
CONTROL_EXCLUDE	K11_LIVER
CONTROL_PRECONDITIONS
CONTROL_CONDITIONS
SEX
INCLUDE
PRE_CONDITIONS
CONDITIONS
OUTPAT_ICD
OUTPAT_OPER
HD_MAINONLY
HD_ICD_10_ATC
HD_ICD_10	K71
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	K71
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

Toxic liver disease

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