RESEARCH - Familial associations of RA with autoimmune diseases and related conditions

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Arthritis Rheum. 2009 Feb 26;60(3):661-668. [Epub ahead of print]

Familial associations of rheumatoid arthritis with autoimmune diseases

and related conditions.

Hemminki K, Li X, Sundquist J, Sundquist K.

German Cancer Research Center, Heidelberg, Germany, and Karolinska

Institute, Huddinge, Sweden.

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).

CONCLUSION: 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.

PMID: 19248111

http://www.ncbi.nlm.nih.gov/pubmed/19248111

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