Familial associations of rheumatoid arthritis with autoimmune diseases and related conditions.
OBJECTIVE
In the era of genome-wide association studies, familial risks are used to estimate disease heritability and the likelihood of candidate-gene identification. This study was undertaken to estimate associations of rheumatoid arthritis (RA) with any of 33 autoimmune diseases and related conditions among parents and offspring, singleton siblings, twins, and spouses.


METHODS
The Multigeneration Register in Sweden was used as a reliable source of information on Swedish families throughout the last century. Data on autoimmune diseases in individual family members were obtained through linkage to the Hospital Discharge Register. The standardized incidence ratio (SIR) was calculated as a measure of the relative risk of RA in family members of patients with RA or any of 33 other autoimmune diseases or related conditions, as compared with the relative risk of RA in those lacking an affected family member.


RESULTS
Among a total of 447,704 patients, 47,361 were diagnosed as having RA. The SIRs for RA were 3.02 in offspring of affected parents, 4.64 in siblings, 9.31 in multiplex families, 6.48 in twins, and 1.17 in spouses. Significant associations with the familial risk of RA in offspring according to parental proband were observed for ankylosing spondylitis (SIR 2.96), localized scleroderma (SIR 2.40), Sjögren's syndrome (SIR 2.25), systemic lupus erythematosus (SIR 2.13), systemic sclerosis (SIR 1.65), Hashimoto thyroiditis/hypothyroidism (SIR 1.54), pernicious anemia (SIR 1.53), sarcoidosis (SIR 1.40), psoriasis (SIR 1.36), Wegener's granulomatosis (SIR 1.34), and asthma or polymyalgia rheumatica (SIR 1.32).


CONCLUSIONS
This is the first study to compare the familial risks of RA in relation to a large number of autoimmune diseases and related conditions using data from a single population. The high discordant familial risks in this population suggest that there is extensive genetic sharing between RA and the associated diseases.
Hemminki
Kari
K
German Cancer Research Center, Heidelberg, Germany, and Karolinska Institute, Huddinge, Sweden. k.hemminki@dkfz.de
Li
Xinjun
X
Sundquist
Jan
J
Sundquist
Kristina
K
D000752:Anemia, Pernicious / Q000208:ethnology / Q000235:genetics; D001172:Arthritis, Rheumatoid / Q000208:ethnology* / Q000235:genetics*; D001249:Asthma / Q000208:ethnology / Q000235:genetics; D001327:Autoimmune Diseases / Q000208:ethnology* / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000208:ethnology* / Q000235:genetics*; D014890:Granulomatosis with Polyangiitis / Q000208:ethnology / Q000235:genetics; D050031:Hashimoto Disease / Q000208:ethnology / Q000235:genetics; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000208:ethnology / Q000235:genetics; D008297:Male; D010375:Pedigree; D011111:Polymyalgia Rheumatica / Q000208:ethnology / Q000235:genetics; D011565:Psoriasis / Q000208:ethnology / Q000235:genetics; D012042:Registries; D012507:Sarcoidosis / Q000208:ethnology / Q000235:genetics; D012594:Scleroderma, Localized / Q000208:ethnology / Q000235:genetics; D035781:Siblings / Q000208:ethnology; D012859:Sjogren's Syndrome / Q000208:ethnology / Q000235:genetics; D013167:Spondylitis, Ankylosing / Q000208:ethnology / Q000235:genetics; D013548:Sweden; D014427:Twins / Q000208:ethnology / Q000235:genetics