Heritability of vasculopathy, autoimmune disease, and fibrosis in systemic sclerosis: a population-based study.
OBJECTIVE
To investigate the familiality of systemic sclerosis (SSc) in relation to Raynaud's phenomenon (RP) (a marker of vasculopathy), other autoimmune inflammatory disease, and fibrotic interstitial lung disease (ILD).


METHODS
A genealogic resource, the Utah Population Database (UPDB), was used to test heritability of RP, other autoimmune disease, and ILD. Diseases were defined by International Classification of Diseases, Ninth Revision codes and identified from statewide discharge data, the University of Utah Health Science Center Enterprise Data Warehouse, and death certificates and were linked to the UPDB for analysis. Familial standardized incidence ratio (FSIR), relative risks (RRs) to first-, second-, third-, and fourth-degree relatives for SSc, RP, other autoimmune disease, and ILD (with 95% confidence intervals [95% CIs]), and population attributable risk (PAR) were calculated.


RESULTS
A software kinship analysis tool was used to analyze 1,037 unique SSc patients. Fifty SSc families had significant FSIRs, ranging from 2.07 to 17.60. The adjusted PAR was approximately 8%. The RRs were significant for other autoimmune disease in the first-degree relatives (2.49 [95% CI 1.99-3.41], P = 2.42 x 10(-15)) and second-degree relatives (1.48 [95% CI 1.34-2.39], P = 0.002), for RP in first-degree relatives (6.38 [95% CI 3.44-11.83], P = 4.04 x 10(-9)) and second-degree relatives (2.39 [95% CI 1.21-4.74], P = 0.012), and for ILD in first-degree relatives (1.53 [95% CI 1.04-2.26], P = 0.03), third-degree relatives (1.47 [95% CI 1.18-1.82], P = 0.0004), and fourth-degree relatives (1.2 [95% CI 1.06-1.35], P = 0.004).


CONCLUSIONS
These data suggest that SSc pedigrees include more RP, autoimmune inflammatory disease, and ILD than would be expected by chance. In SSc pedigrees, genetic predisposition to vasculopathy is the most frequent risk among first-degree relatives.
Frech
Tracy
T
University of Utah, Division of Rheumatology, Department of Medicine, Salt Lake City, UT 84132, USA. tracy.frech@hsc.utah.edu
Khanna
Dinesh
D
Markewitz
Boaz
B
Mineau
Geraldine
G
Pimentel
Richard
R
Sawitzke
Allen
A
D001327:Autoimmune Diseases / Q000453:epidemiology / Q000235:genetics*; D002423:Cause of Death; D015897:Comorbidity; D005192:Family Health; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D017563:Lung Diseases, Interstitial / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D010375:Pedigree; D011928:Raynaud Disease / Q000453:epidemiology / Q000235:genetics*; D012595:Scleroderma, Systemic / Q000150:complications / Q000235:genetics*; D014589:Utah / Q000453:epidemiology