Risteys · L12_LOCALDCONNECTISSUEOTH

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 — L94 Cause of death: ICD-10 — L94 2 out of 7 registries used, show all original rules.	682
4. Check minimum number of events None	682
5. Include endpoints L12_LOCALSCLERODERMA L12_LINEARSCLERODERMA L12_CALCINOSISCUTIS L12_SCLERODACTYLY L12_GOTTRONPAPULES L12_POIKILODERMAVASCULAREATROPH L12_AINHUM L12_LOCALCONNECTISSUENAS	702
6. Filter based on genotype QC (FinnGen only)	702

Summary Statistics

↥

-FinRegistry-

Key figures

	All	Female	Male
Number of individuals
Whole population	4269	3191	1056
Only index persons	3949	2982	967
Unadjusted period prevalence (%)
Whole population	0.08	0.09	0.03
Only index persons	0.09	0.11	0.04
Median age at first event (years)
Whole population	53.91	55.68	48.45
Only index persons	53.10	55.18	46.69

-FinnGen-

Key figures

	All	Female	Male
Number of individuals	702	557	145
Unadjusted period prevalence (%)	0.16	0.19	0.06
Median age at first event (years)	55.86	55.95	55.55

-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
632: Matched controls
6318

Code

Vocabulary

Description

Odds Ratio

-log₁₀(p)

N matched cases

N matched controls

L94.0

ICD-10 Finland

Localized scleroderma [morphea]

+∞

323.0

452

TQX10

NOMESCO Finland

Biopsy of skin and subcutaneous tissue

15.9

142.4

253

254

L94.9

ICD-10 Finland

Localized connective tissue disorder, unspecified

+∞

62.5

L94.8

ICD-10 Finland

Other specified localized connective tissue disorders

+∞

52.9

L94.2

ICD-10 Finland

Calcinosis cutis

+∞

52.9

D07AD01

ATC

clobetasol; topical

4.6

47.6

194

554

D07AC01

ATC

betamethasone; topical

3.5

47.5

328

1484

M34.9

ICD-10 Finland

Systemic sclerosis, unspecified

99.1

42.4

D07AC13

ATC

mometasone; topical

3.4

42.2

275

1159

L97

ICD-10 Finland

Ulcer of lower limb, not elsewhere classified

31.6

41.6

L90.0

ICD-10 Finland

Lichen sclerosus et atrophicus

26.0

40.9

L30.9

ICD-10 Finland

Dermatitis, unspecified

3.8

38.9

195

657

E0000UV

ATC

3.0

37.5

339

1758

P01BA02

ATC

hydroxychloroquine; oral

5.1

36.8

127

296

L94.1

ICD-10 Finland

Linear scleroderma

+∞

35.8

L98.4

ICD-10 Finland

Chronic ulcer of skin, not elsewhere classified

40.8

33.8

L04AX03

ATC

methotrexate; systemic (immunosuppressants)

4.7

33.0

123

309

M34.1

ICD-10 Finland

CR(E)ST syndrome

49.6

27.7

70100

ICD-8 Finland

Other hypertrophic and atrophic conditions of the skin, Seleroderma circumscriptum NUD

+∞

25.2

202

Kela drug reimbursment

Connective tissue diseases, rheumatoid arthritis and comparable disease

3.6

23.7

118

379

L95.9

ICD-10 Finland

Vasculitis limited to skin, unspecified

+∞

22.0

H02AB06

ATC

prednisolone; systemic

2.3

21.9

335

2088

E000001

ATC

2.7

21.4

173

772

GD1AA

NOMESCO Finland

Thorax X-ray examination

2.3

21.3

301

1800

M34.0

ICD-10 Finland

Progressive systemic sclerosis

62.2

21.0

XQ848

NOMESCO Finland

Dermatological photography

9.1

19.9

R21

ICD-10 Finland

Rash and other nonspecific skin eruption

5.4

19.7

123

NK4XE

NOMESCO Finland

Joint ultrasound examination not elsewhere classified

4.2

19.4

197

XX9XE

NOMESCO Finland

Other ultrasound examination

12.8

18.8

L04AA01

ATC

[U] ciclosporin; systemic

11.5

18.4

L04AA06

ATC

mycophenolic acid; systemic

9.3

17.9

L04AX01

ATC

azathioprine; systemic

5.2

17.7

116

C08CA05

ATC

nifedipine; systemic

4.0

17.7

198

QDG20

NOMESCO Finland

Operation for chronic ulcer or fistula of skin of lower limb

32.5

17.1

D07AB08

ATC

desonide; topical

3.2

17.1

350

D02AE01

ATC

carbamide; topical

4.0

17.0

195

M34.8

ICD-10 Finland

Other forms of systemic sclerosis

65.2

16.8

ND2AA

NOMESCO Finland

Hand and fingers X-ray examination

3.4

16.5

277

UJD10

NOMESCO Finland

Esophagoscopy, gastroscopy and duodenoscopy

2.2

16.3

210

1165

QDB10

NOMESCO Finland

Major dressing of wound of skin of lower limb

5.2

15.6

101

A46

ICD-10 Finland

Erysipelas

2.9

15.3

371

TQW80

NOMESCO Finland

Local dermatologic skincare

7.1

15.2

138

Kela drug reimbursment

Severe anaemia associated with chronic renal failure

9.8

15.1

M35.9

ICD-10 Finland

Systemic involvement of connective tissue, unspecified

8.9

14.4

M32.9

ICD-10 Finland

Systemic lupus erythematosus, unspecified

22.9

14.3

D02AX

ATC

Other emollients and protectives

5.5

13.9

L98.9

ICD-10 Finland

Disorder of skin and subcutaneous tissue, unspecified

34.9

13.6

L93.0

ICD-10 Finland

Discoid lupus erythematosus

143.0

13.5

L92.0

ICD-10 Finland

Granuloma annulare

143.0

13.5

TK800

NOMESCO Finland

Hemodialysis

8.4

13.4

I73.0

ICD-10 Finland

Raynaud syndrome

7.5

13.4

ZXD30

NOMESCO Finland

Difficulties in perfomrming procedure

4.7

13.2

102

J01FF01

ATC

clindamycin; systemic

2.1

13.2

186

1055

L04AD01

ATC

ciclosporin; systemic

9.0

13.1

190

Kela drug reimbursment

Lanthanum carbonate, sevelamer and sucroferric oxyhydroxide

14.4

12.8

NK6QA

NOMESCO Finland

Measurement of bone density from tow or more locations with X-ray

3.2

12.7

234

XQ841

NOMESCO Finland

Examination of dermatosis with microscope

32.8

12.6

127

Kela drug reimbursment

Transplant complication

11.3

12.6

D07AB02

ATC

hydrocortisone butyrate; topical

2.0

12.4

197

1169

XPX99

NOMESCO Finland

Other diagnostic examination of periferal vessel

3.8

12.3

150

S97

ICPC

Chronic ulcer skin

4.0

11.4

118

PBL10

NOMESCO Finland

Construction of arteriovenous fistula from radial artery

12.1

11.4

QDB05

NOMESCO Finland

Revision of wound of skin of lower limb

7.5

11.3

A49.9

ICD-10 Finland

Bacterial infection, unspecified

2.8

11.1

274

Z49.1

ICD-10 Finland

Extracorporeal dialysis

10.8

C03CA01

ATC

furosemide; systemic

2.0

10.7

164

952

JN1AE

NOMESCO Finland

Ultrasound examination of upper part of abdomen

2.8

10.6

280

123

Kela drug reimbursment

Chronic disorders of vitamin D metabolism

7.0

10.5

L95.8

ICD-10 Finland

Other vasculitis limited to skin

111.8

10.4

M34

ICD-10 Finland

Systemic sclerosis

111.8

10.4

L95.0

ICD-10 Finland

Livedoid vasculitis

+∞

10.4

L94.3

ICD-10 Finland

Sclerodactyly

+∞

10.4

NH3AA

NOMESCO Finland

Foot and toes X-ray examination

2.8

10.3

262

XPX04

NOMESCO Finland

Angioscopy

19.2

10.3

I83.0

ICD-10 Finland

Varicose veins of lower extremities with ulcer

7.7

10.3

M13.9

ICD-10 Finland

Arthritis, unspecified

3.0

10.2

209

D05AX02

ATC

calcipotriol; topical

4.7

10.2

A12AX

ATC

Calcium, combinations with vitamin D and/or other drugs

1.8

10.1

239

1605

S18

ICPC

Laceration/cut

1.8

10.0

259

1790

L01BA01

ATC

methotrexate; systemic (folic acid analog.)

4.1

10.0

E000006

ATC

2.9

9.9

224

E000007

ATC

3.2

9.6

165

SPAT1262

SPAT

Handing over of treatment supplies

2.1

9.6

115

603

V03AE02

ATC

sevelamer; oral

17.9

9.4

N03AX16

ATC

pregabalin; oral

1.9

9.4

159

952

H02AB04

ATC

methylprednisolone; systemic

2.2

9.3

105

533

A12AA04

ATC

calcium carbonate; oral

7.5

9.3

SPAT1148

SPAT

Treatment of chronic ulcer or burn

2.3

9.3

406

TNX10

NOMESCO Finland

Arthrocentesis, unspecified region, unspecified region

2.8

9.1

230

196

Kela drug reimbursment

Paricalcitol and cinacalcet

15.9

9.1

A11CC03

ATC

alfacalcidol; systemic

5.6

9.0

PG1DE

NOMESCO Finland

Other extensive ultrasound examination of artery

3.7

8.9

108

M04AA01

ATC

allopurinol; systemic

2.5

8.8

306

E000002

ATC

2.2

8.7

434

V03AE01

ATC

polystyrene sulfonate; oral

10.2

8.6

NH3DA

NOMESCO Finland

Bilateral foot X-ray examination

5.0

8.5

N18.0

ICD-10 Finland

End-stage renal disease

13.0

8.4

D01AC20

ATC

imidazoles/triazoles in combination with corticosteroids; topical

1.9

8.4

148

896

7101A

ICD-9 Finland

Diffuse diseases of connective tissue, Systemic sclerosis[SCLERODERMA]

+∞

8.3

WXQ10

NOMESCO Finland

Psoralen - Ultraviolet A therapy with systemic sensitivisation

+∞

8.3

N18.8

ICD-10 Finland

Other chronic renal failure

5.3

8.2

ZXD10

NOMESCO Finland

Scheduled procedure

1.7

8.2

248

1766

GD1DD

NOMESCO Finland

High resolution CT examination of lungs

3.4

8.2

116

NHQ40

NOMESCO Finland

Amputation of toe

11.9

8.1

L89

ICD-10 Finland

Decubitus ulcer and pressure area

33.8

8.1

E03.9

ICD-10 Finland

Hypothyroidism, unspecified

2.1

8.1

464

Z3226

NOMESCO Finland

Physiotherapist

1.9

8.0

124

714

ZXE10

NOMESCO Finland

More than one and less than three hours

1.7

8.0

230

1610

Z2221

NOMESCO Finland

Medical doctor

1.7

8.0

186

1224

M25.5

ICD-10 Finland

Pain in joint

1.7

8.0

190

1263

I70.2

ICD-10 Finland

Atherosclerosis of arteries of extremities

2.9

8.0

164

E000003

ATC

3.3

8.0

119

J01MA02

ATC

ciprofloxacin; systemic

1.7

7.9

225

1570

E10.2

ICD-10 Finland

Type 1 diabetes mellitus, With renal complications

11.0

7.8

M32.0

ICD-10 Finland

Drug-induced systemic lupus erythematosus

45.5

7.7

WXQ12

NOMESCO Finland

Psoralen - Ultraviolet A therapy with local sensitivisation

18.6

7.6

R06AE07

ATC

cetirizine; oral

1.6

7.6

287

2156

137

Kela drug reimbursment

Uraemia requiring dialysis

10.2

7.6

Z94.0

ICD-10 Finland

Kidney transplant status

10.2

7.6

TPH30

NOMESCO Finland

Insertion of central venous catheter through periferal vein

7.2

7.5

QBA99

NOMESCO Finland

Other local destruction of skin of trunk

13.6

7.4

GD1PA

NOMESCO Finland

X-ray examination of the lungs in one projection

2.6

7.4

211

L94

ICD-10 Finland

Other localized connective tissue disorders

+∞

7.3

TQW11

NOMESCO Finland

Vacuum treatment of wound

6.4

7.3

320

Kela drug reimbursment

Lanthanum carbonate, sevelamer and sucroferric oxyhydroxide

16.0

7.2

ND2DA

NOMESCO Finland

Bilateral hand X-ray examination

4.8

7.1

KAS10

NOMESCO Finland

Allogenic transplantation of kidney from cadaver donor

10.2

7.1

JN3AE

NOMESCO Finland

Abdominal ultrasound examination

2.0

6.9

453

I10

ICD-10 Finland

Essential (primary) hypertension

1.6

6.9

322

2531

I15.1

ICD-10 Finland

Hypertension secondary to other renal disorders

8.4

6.9

R4120

NOMESCO Finland

Occupational therapy

2.7

6.8

176

L04AD02

ATC

tacrolimus; systemic (calcineurin inhibitors)

9.5

6.8

RJ411

NOMESCO Finland

40.5

6.8

NHQ30

NOMESCO Finland

Amputation of foot, transmetatarsal

40.5

6.8

QXA05

NOMESCO Finland

Skin division, unspecified location

40.5

6.8

ZXE00

NOMESCO Finland

One hour or less

1.6

6.7

248

1837

B03XA03

ATC

methoxy polyethylene glycol-epoetin beta; parenteral

22.8

6.7

PF1AT

NOMESCO Finland

Intravascular dilatation of arteries of knee, lower leg and ankle (PTA)

22.8

6.7

R4110

NOMESCO Finland

Physiotherapy

1.7

6.7

164

1089

M35.0

ICD-10 Finland

Sicca syndrome [Sjögren]

4.1

6.7

J01DB01

ATC

cefalexin; oral

1.7

6.6

505

4446

R06AX27

ATC

desloratadine; oral

1.7

6.6

179

1219

N18.9

ICD-10 Finland

Chronic kidney disease, unspecified

3.0

6.6

125

A02BC02

ATC

pantoprazole; systemic

1.6

6.6

395

3271

H02AB07

ATC

prednisone; oral

1.9

6.6

548

J01DA01

ATC

[U] cefalexin; systemic

1.5

6.6

375

3073

QDA10

NOMESCO Finland

Incision of skin of lower limb

10.2

6.6

H04.10

ICD-10 Finland

Dry eye syndrome

2.1

6.5

354

QAA25

NOMESCO Finland

Destruction of lesion of head or neck

5.8

6.5

NG4AA

NOMESCO Finland

Lower leg X-ray examination

4.0

6.4

E10.5

ICD-10 Finland

Type 1 diabetes mellitus, With peripheral circulatory complications

70.5

6.4

G73.7*M34.8

ICD-10 Finland

Myopathy in scleroderma

70.5

6.4

L91.0

ICD-10 Finland

Hypertrophic scar

14.5

6.4

N08.39*E10.2

ICD-10 Finland

Insulin-dependent diabetes mellitus - Diabetic nephropathy

14.5

6.4

E10.7

ICD-10 Finland

Type 1 diabetes mellitus, With multiple complications

5.3

6.4

S99

ICPC

Skin disease other

5.3

6.4

7100A

ICD-9 Finland

Diffuse diseases of connective tissue, Systemic lupus erythematosus

+∞

6.3

L94.4

ICD-10 Finland

Gottron papules

+∞

6.3

RJ412

NOMESCO Finland

+∞

6.3

L84

ICD-10 Finland

Corns and callosities

4.2

6.3

DM1QA

NOMESCO Finland

Paranasal sinuses X-ray examination in one projection

2.8

6.2

143

L71.8

ICD-10 Finland

Other rosacea

5.8

6.2

A10AC01

ATC

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

2.6

6.2

180

N02AX02

ATC

tramadol; systemic, rectal

1.5

6.1

244

1828

N08.39*E11.2

ICD-10 Finland

Non-insulin-dependent diabetes mellitus - Diabetic nephropathy

8.7

6.1

FM1AE

NOMESCO Finland

Standard cardiac ultrasound examination

1.8

6.1

572

Mortality – FinRegistry

↥

Association

Association between endpoint L12_LOCALDCONNECTISSUEOTH and mortality.

Females

Parameter	HR [95% CI]	p-value
L12_LOCALDCONNECTISSUEOTH	1.609 [1.39, 1.87]	< 0.001
Birth year	0.987 [0.98, 1.0]	0.004

During the follow-up period (1.1.1998 — 31.12.2019), 414 out of 2658 females with L12_LOCALDCONNECTISSUEOTH died.

Males

Parameter	HR [95% CI]	p-value
L12_LOCALDCONNECTISSUEOTH	1.885 [1.5, 2.36]	< 0.001
Birth year	0.985 [0.98, 0.99]	0.003

During the follow-up period (1.1.1998 — 31.12.2019), 166 out of 878 males with L12_LOCALDCONNECTISSUEOTH died.

Mortality risk

Mortality risk for people of age

years, who have L12_LOCALDCONNECTISSUEOTH.

N-year risk	Females	Males
1	0.132%	0.253%
5	0.812%	1.947%
10	1.838%	5.043%
15	3.557%	9.345%
20	6.019%	15.559%

Relationships between endpoints

↥

Index endpoint: L12_LOCALDCONNECTISSUEOTH – Other localized connective tissue disorders

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	L12_LOCALDCONNECTISSUEOTH
CONTROL_EXCLUDE	L12_OTHERSKINSUBCUTIS
CONTROL_PRECONDITIONS
CONTROL_CONDITIONS
SEX
INCLUDE	L12_LOCALSCLERODERMA\|L12_LINEARSCLERODERMA\|L12_CALCINOSISCUTIS\|L12_SCLERODACTYLY\|L12_GOTTRONPAPULES\|L12_POIKILODERMAVASCULAREATROPH\|L12_AINHUM\|L12_LOCALCONNECTISSUENAS
PRE_CONDITIONS
CONDITIONS
OUTPAT_ICD
OUTPAT_OPER
HD_MAINONLY
HD_ICD_10_ATC
HD_ICD_10	L94
HD_ICD_9
HD_ICD_8
HD_ICD_10_EXCL
HD_ICD_9_EXCL
HD_ICD_8_EXCL
COD_MAINONLY
COD_ICD_10	L94
COD_ICD_9
COD_ICD_8
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

Other localized connective tissue disorders

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