Rheumatic diseases Task Force Refined phenotypes

This data includes 1) curated phenotypes with adjusted disease onset from Rheumatic diseases Task Force diseases of interest: Rheumatoid arthritis (RA, seropositive and negative), Ankylosing spondylitis, Psoriatic arthritis (PsA), Systemic lupus erythematous (SLE), Systemic scleroderma (SSc), Mixed connective tissue diseases (MCTD) and Sjögren’s syndrome; 2) Rheumatoid arthritis severity class defined by medication usage

The data is available in the following Sandbox directory:

/finngen/library-red/task_force_data/Rheumatic_diseases/Refined_phenotypes/

## Data fields for curated phenotypes

Field Description

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FINNGENID FINNGENID of the subject

[PHENOTYPE] Name of each phenotype and specification of inclusion criteria (e.g. MIN2DX = minimum of 2 diagnosis required from hospital records). 1= cases, 0 = controls (same control definition used as for corresponding core endpoint), NA

[PHENOTYPE]_EVENT_AGE Age at diagnosis

[PHENOTYPE]_APPROX_EVENT_DAY Approximate diagnosis date (randomized +/- 1-15 days from

the exact date)

##Data specifics for curated phenotypes

Phenotypes have been curated by Examining the effect of published variants for different phenotype definitions for each disease and selected single definition that maximised the explanatory power of those published variants. Expanded source data to primary care to identify earliest relevant event in each disease to capture more realistic first diagnosis dates.

For Rheumatoid arthritis, more specific curation has been conducted:

Phenotype includes patients with at least three RA diagnoses (ICD-8 codes 7121, 7122, 7123, ICD-9 codes 7140, 7141, 7142 and ICD-10 codes M05, M06) made during internal medicine or rheumatology inpatient or outpatient visits at the age of 16 years or older.

Exclusions:

Patients with recorded juvenile arthritis diagnoses (ICD-8 7120, ICD-9 7143, ICD-10 M08) have been excluded.

Adjusted disease onset date:

For included patients, the disease onset date was redefined as the earliest event date of any of the following events:

- Diagnosis of RA (ICD-8 codes 7121, 7122, 7123, ICD-9 codes 7140, 7141, 7142 and ICD-10 codes M05, M06), other arthritis (ICD-10 code M13), palindromic rheumatism (ICD-10 code M12.3) or alia definita including palindromic arthritis (ICD-9 code 7148) on a hospital inpatient or outpatient visit or on a primary health care visit.

- Any medical reimbursement granted with the previously mentioned diagnoses.

- Reimbursement code 202 (diffuse connective tissue diseases, rheumatic arthritis and similar conditions), with any diagnosis.

Additional exclusion after onset adjustment:

Patients whose earliest qualifying event occurred before age 16 years were excluded.

## Data fields for Rheumatoid arthritis severity phenotypes

Field Description

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FINNGENID FINNGENID of the subject

SEVERITY Defined severity class (MILD_RA, MODERATE_RA, SEVERE_RA)

APPROX_EVENT_DAY First qualifying event for severity class (MILD_RA = first DMARD purchase, MODERATE_RA = first biologic/JAK inhibitor, SEVERE_RA = third biologic/JAK inhibitor. Dates are randomized as usual ( +/- 1-15 days from the exact date)

##Data specifics for Rheumatoid arthritis severity phenotypes

Curated Rheumatoid arthritis phenotype (minimum of 3 diagnosis from specialty) has been used as basis for defining severity classes. Disease severity has been defined by medication usage.

Mild RA: Controlled with conventional DMARDs, no biologics or JAK inhibitors used. Limited to diagnosis 2000 onwards and minimum 5 year of follow-up time. N = 4622

Moderate RA: Required 1–2 biologic DMARDs or JAK inhibitors in addition to DMARDs. Minimum 5 year of follow-up time. N = 2267

Severe / Refractory RA: Needed ≥3 different bDMARDs or JAK inhibitors over time. No minimum follow-up time. N = 1009