Risteys · E4_GRAVES_OPHT

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 — H06.2E05.9 Cause of death:* ICD-10 — H06.2*E05.9 2 out of 7 registries used, show all original rules.	786
4. Check minimum number of events None	786
5. Include endpoints None	786
6. Filter based on genotype QC (FinnGen only)	786

Summary Statistics

↥

-FinRegistry-

Key figures

	All	Female	Male
Number of individuals
Whole population	3679	2975	690
Only index persons	3569	2906	663
Unadjusted period prevalence (%)
Whole population	0.07	0.09	0.02
Only index persons	0.09	0.11	0.03
Median age at first event (years)
Whole population	51.38	51.28	51.88
Only index persons	51.22	51.20	51.31

-FinnGen-

Key figures

	All	Female	Male
Number of individuals	786	643	143
Unadjusted period prevalence (%)	0.19	0.22	0.06
Median age at first event (years)	52.41	51.98	54.33

-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
675: Matched controls
6749

Code

Vocabulary

Description

Odds Ratio

-log₁₀(p)

N matched cases

N matched controls

E05.9

ICD-10 Finland

Thyrotoxicosis, unspecified

89.3

323.0

356

H06.2*E05.9

ICD-10 Finland

Dysthyroid exophthalmos

4503599627370496.0

323.0

668

H03BB01

ATC

carbimazole; oral

160.3

323.0

527

146

E05.0

ICD-10 Finland

Thyrotoxicosis with diffuse goitre

461.6

323.0

580

H03AA01

ATC

levothyroxine sodium; systemic

22.1

257.5

562

1240

BAA60

NOMESCO Finland

Total thyroidectomy

47.4

196.9

241

H06.2

ICD-10 Finland

Dysthyroid exophthalmos

2197.1

176.0

163

H062, E050

ICD-10 Finland

499.3

162.9

156

104

Kela drug reimbursment

Thyroid insufficiency

14.1

140.7

265

296

E89.01

ICD-10 Finland

Postsurgical hypothyroidism

36.3

129.5

168

S01XA20

ATC

artificial tears and other indifferent preparations; ophthalmic

7.9

125.0

530

2127

CA1BG

NOMESCO Finland

Eye and orbita MRI examination with high intensity magnet

163.8

106.7

110

E89.00

ICD-10 Finland

Postirradiation hypothyroidism

56.3

85.7

101

A12AX

ATC

Calcium, combinations with vitamin D and/or other drugs

4.9

81.8

415

1650

H53.2

ICD-10 Finland

Diplopia

20.9

77.2

117

E05

ICD-10 Finland

Thyrotoxicosis [hyperthyroidism]

44.0

76.9

H05.2

ICD-10 Finland

Exophthalmic conditions

97.8

71.7

C07AA05

ATC

propranolol; systemic

4.9

69.2

287

880

H50.2

ICD-10 Finland

Vertical strabismus

81.4

65.6

CA1CG

NOMESCO Finland

Eye and orbita extensive MRI examination with high intensity magnet

42.2

58.0

XCW99

NOMESCO Finland

Other investigative procedure of eye

5.4

49.6

166

381

XCK00

NOMESCO Finland

Perimetry

7.1

49.5

131

222

CAC30

NOMESCO Finland

Decompression of orbit to sinuses

+∞

48.5

H02AB06

ATC

prednisolone; systemic

3.2

45.5

430

2376

CAC44

NOMESCO Finland

Combined decompression of orbit

+∞

34.7

CEC00

NOMESCO Finland

Recession of extraocular muscle

68.8

34.4

CA1AD

NOMESCO Finland

Orbita CT

184.2

34.1

ZX120

NOMESCO Finland

Intravenous

4.5

34.0

132

344

EP1AE

NOMESCO Finland

Neck ultrasound examination

5.5

31.9

100

206

ZXA10

NOMESCO Finland

Bilateral

3.2

31.5

197

761

Z01.0

ICD-10 Finland

Examination of eyes and vision

3.4

31.4

181

659

BA1AE

NOMESCO Finland

Thyroiid ultrasound examination

12.9

30.3

H50.6

ICD-10 Finland

Mechanical strabismus

304.3

29.0

E06.2

ICD-10 Finland

Chronic thyroiditis with transient thyrotoxicosis

156.7

28.9

H50.8

ICD-10 Finland

Other specified strabismus

151.2

27.8

E05.2

ICD-10 Finland

Thyrotoxicosis with toxic multinodular goitre

14.4

27.2

H50.0

ICD-10 Finland

Convergent concomitant strabismus

29.1

26.9

A02BC02

ATC

pantoprazole; systemic

2.6

26.8

501

3563

TPH04

NOMESCO Finland

Cathetrisation of vein

2.9

26.8

195

825

XCD10

NOMESCO Finland

Electrophysiological examination of eye

9.7

26.7

WF099

NOMESCO Finland

Other radiotherapy

54.0

26.4

CAC20

NOMESCO Finland

Lateral decompression of orbit

+∞

26.2

CBK00

NOMESCO Finland

Myotomy or resection of tarsal muscle or levator muscle of eyelid for correction of retraction

+∞

25.2

H02AB07

ATC

prednisone; oral

3.1

24.4

151

567

H04.10

ICD-10 Finland

Dry eye syndrome

3.5

24.3

124

405

E03.9

ICD-10 Finland

Hypothyroidism, unspecified

3.2

24.1

143

522

2AB04

NOMESCO Finland

90.0

23.8

T86

ICPC

Hypothyroidism/myxoedema

5.6

21.7

126

E03.89

ICD-10 Finland

Other specified hypothyroidism

5.8

21.3

116

T85

ICPC

Hyperthyroidism/thyrotoxicosis

18.0

20.2

C07AB07

ATC

bisoprolol; oral

2.2

20.0

334

2111

L04AX03

ATC

methotrexate; systemic (immunosuppressants)

3.3

19.6

107

363

E05.1

ICD-10 Finland

Thyrotoxicosis with toxic single thyroid nodule

31.0

18.4

H02.5

ICD-10 Finland

Other disorders affecting eyelid function

45.3

18.3

DM1AD

NOMESCO Finland

CT of paranasal sinuses and face area

5.2

18.3

120

Z03.80

ICD-10 Finland

Observation for other suspected diseases and conditions

6.3

18.2

E05.5

ICD-10 Finland

Thyroid crisis or storm

184.6

17.6

CEW99

NOMESCO Finland

Other operation on extraocular muscle

51.4

17.1

XCK10

NOMESCO Finland

Photography of fundus of eye

3.1

16.8

347

CEC90

NOMESCO Finland

Total transposition of extraocular muscle or muscles

+∞

16.7

CEC10

NOMESCO Finland

Recession and resection of extraocular muscle

18.5

16.6

CS444

NOMESCO Finland

Visual field testing with Octopus automated perimetry

5.8

16.2

CA1CM

NOMESCO Finland

Eye and orbita extensive MRI examination with 3 Tesla magnet

34.3

15.8

E03

ICD-10 Finland

Other hypothyroidism

3.5

15.5

238

YA1BD

NOMESCO Finland

Extensive CT examination of head and neck for dose design of radiotherapy

18.3

15.2

CEC60

NOMESCO Finland

Transposition of extraocular muscle with adjustable suture

46.1

15.1

GD1AA

NOMESCO Finland

Thorax X-ray examination

1.9

14.6

298

1953

WX408

NOMESCO Finland

General anesthesy, balanced

2.1

14.6

217

1259

CA1BM

NOMESCO Finland

Eye and orbita MRI examination with 3 Tesla magnet

153.1

14.5

E89.2

ICD-10 Finland

Postprocedural hypoparathyroidism

16.2

14.0

S01CA01

ATC

dexamethasone and antiinfectives; ophthalmic (ophth., corticosteroids and antiinfectives in comb.)

2.0

13.5

241

1492

E03.2

ICD-10 Finland

Hypothyroidism due to medicaments and other exogenous substances

18.7

13.4

CK2X4

NOMESCO Finland

Optical coherence tomography (OCT) of ocular fundus

3.0

13.3

289

XX7CT

NOMESCO Finland

Radioiodine therapy of thydoid tissue

10.8

12.8

N05CF01

ATC

zopiclone; oral

1.9

12.5

233

1457

ZX012

NOMESCO Finland

Radiotherapy with large shaped fields - isocentric therapy

3.4

12.3

188

CK2S4

NOMESCO Finland

Plain photography of ocular fundus

3.4

12.2

194

O99.2

ICD-10 Finland

Endocrine, nutritional and metabolic diseases complicating pregnancy, childbirth and the puerperium

7.8

11.2

CE2W4

NOMESCO Finland

Eye movement mapping

44.1

10.9

YX8BD

NOMESCO Finland

Stereotactic extensive CT examination for dose design of radiotherapy

28.5

10.8

A11CC03

ATC

alfacalcidol; systemic

5.6

10.5

WX002

NOMESCO Finland

Sedation and analgesia

2.0

10.4

142

784

1XC02

NOMESCO Finland

10.8

10.3

AAG50

NOMESCO Finland

Stereotactic intracranial radiotherapy

19.1

10.3

CS494

NOMESCO Finland

Other visual field testing

5.0

10.2

E89.09

ICD-10 Finland

Postprocedural hypothyroidism, other or several procedures

26.4

9.8

E89.0

ICD-10 Finland

Postprocedural hypothyroidism

55.8

9.7

C03EA01

ATC

hydrochlorothiazide and potassium-sparing agents; oral

2.0

9.0

119

647

CS424

NOMESCO Finland

Visual field testing with Goldmann perimetry

12.7

8.9

E03.80

ICD-10 Finland

Hypothyroidism caused by autoimmune thyroiditis

4.5

8.8

WF002

NOMESCO Finland

Radical radiotherapy

3.4

8.8

125

H03BA02

ATC

propylthiouracil; oral

50.6

8.7

J38.0

ICD-10 Finland

Paralysis of vocal cords and larynx

4.8

8.2

WX402

NOMESCO Finland

General anaesthesia

1.9

8.1

123

699

106

Kela drug reimbursment

Hypoparathyroidism

11.9

8.1

TCC40

NOMESCO Finland

Closure of lacrimal canaliculus with plug

22.3

8.0

S01KA02

ATC

hypromellose; ophthalmic

5.0

8.0

E05.80

ICD-10 Finland

Subacute thyrotoxicosis

8.6

7.8

CD2S4

NOMESCO Finland

Photography of eye

18.6

7.6

ZX050

NOMESCO Finland

Stereotactic radiotherapy

12.0

7.6

CB9S4

NOMESCO Finland

Photography of eyelids and eyebrows

25.3

7.6

E05.89

ICD-10 Finland

Other thyrotoxicosis

10.2

7.6

A11CC02

ATC

dihydrotachysterol; oral

13.5

7.4

H57.1

ICD-10 Finland

Ocular pain

3.3

7.3

110

E83.51

ICD-10 Finland

Hypocalcemia

11.0

7.3

CS434

NOMESCO Finland

Visual field testing with Humphrey automated perimetry

4.6

6.8

H50.1

ICD-10 Finland

Divergent concomitant strabismus

9.4

6.8

H50.9

ICD-10 Finland

Strabismus, unspecified

40.4

6.8

2420A

ICD-9 Finland

Thyrotoxicosis with or without goitre, Toxic diffuse goitre

40.4

6.8

H01CB02

ATC

octreotide; parenteral

22.8

6.7

S01EE01

ATC

latanoprost; ophthalmic

2.8

6.6

149

YA1AD

NOMESCO Finland

CT examination of head and neck for dose design of radiotherapy

6.9

6.5

H50.52

ICD-10 Finland

Exophoria

6.9

6.5

ZXC95

NOMESCO Finland

Use of surgical navigator

5.8

6.5

ZXA00

NOMESCO Finland

Right side

1.6

6.5

174

1178

CBK99

NOMESCO Finland

Other operation for retraction of eyelid

70.5

6.4

CAB00

NOMESCO Finland

Anterior orbitotomy with excision of lesion

70.5

6.4

E03.0

ICD-10 Finland

Congenital hypothyroidism with diffuse goitre

7.5

6.4

J44.8

ICD-10 Finland

Other specified chronic obstructive pulmonary disease

2.4

6.4

209

H02AB09

ATC

hydrocortisone; systemic

3.9

6.3

WX140

NOMESCO Finland

Parabulbar anesthesy

3.2

6.3

101

H50.50

ICD-10 Finland

Alternating hyperphoria

+∞

6.3

E50.0

ICD-10 Finland

Vitamin A deficiency with conjunctival xerosis

+∞

6.3

G73.0*E05.9

ICD-10 Finland

Myasthenic syndromes in thyrotoxicosis [hyperthyroidism]

+∞

6.3

N07BA03

ATC

varenicline; oral

2.7

6.2

152

R5110

NOMESCO Finland

Evaluation of the need for aids, the testing, fitting and choice of the aid, instruction in use and delivery of it

2.0

6.2

444

XX3DW

NOMESCO Finland

Time consuming IT work

2.0

6.2

391

S01GX01

ATC

cromoglicic acid; ophthalmic

1.7

6.2

153

1012

R00.0

ICD-10 Finland

Tachycardia, unspecified

3.0

6.0

110

Mortality – FinRegistry

↥

Association

Association between endpoint E4_GRAVES_OPHT_STRICT and mortality.

Females

Parameter	HR [95% CI]	p-value
E4_GRAVES_OPHT_STRICT	1.019 [0.88, 1.18]	0.809
Birth year	0.997 [0.99, 1.01]	0.467

During the follow-up period (1.1.1998 — 31.12.2019), 232 out of 2730 females with E4_GRAVES_OPHT_STRICT died.

Males

Parameter	HR [95% CI]	p-value
E4_GRAVES_OPHT_STRICT	0.955 [0.75, 1.22]	0.706
Birth year	0.988 [0.98, 1.0]	0.021

During the follow-up period (1.1.1998 — 31.12.2019), 86 out of 636 males with E4_GRAVES_OPHT_STRICT died.

Mortality risk

Mortality risk for people of age

years, who have E4_GRAVES_OPHT_STRICT.

N-year risk	Females	Males
1	0.132%	0.18%
5	0.714%	1.192%
10	1.575%	3.121%
15	2.786%	5.749%
20	5.019%	9.82%

Relationships between endpoints

↥

Index endpoint: E4_GRAVES_OPHT_STRICT – Graves ophthalmopathy, strict

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_GRAVES_OPHT_STRICT
CONTROL_EXCLUDE
CONTROL_PRECONDITIONS
CONTROL_CONDITIONS
SEX
INCLUDE
PRE_CONDITIONS
CONDITIONS
OUTPAT_ICD
OUTPAT_OPER
HD_MAINONLY
HD_ICD_10_ATC
HD_ICD_10	H062&E059
HD_ICD_9
HD_ICD_8
HD_ICD_10_EXCL
HD_ICD_9_EXCL
HD_ICD_8_EXCL
COD_MAINONLY
COD_ICD_10	H062&E059
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

Graves ophthalmopathy, strict

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