Familial association between type 1 diabetes and other autoimmune and related diseases.
OBJECTIVE
In the era of genome-wide association studies, familial risks are used to estimate disease heritability and success in gene identification. We wanted to estimate associations between type 1 diabetes mellitus and 33 autoimmune and related diseases in parents, offspring, singleton siblings and twins.


METHODS
The availability of a Multigeneration Register in Sweden provides reliable access to families throughout the last century. The diseases in individual family members were obtained through linkage to the Hospital Discharge Register. Standardised incidence ratios (SIRs) were calculated as relative risks of contracting type 1 diabetes in family members of affected patients compared with those lacking affected family members.


RESULTS
Among a total of 450,899 patients, 21,168 were diagnosed with type 1 diabetes. Familial cases amounted to 10.3% of all type 1 diabetes patients. SIR for type 1 diabetes was 8.23 in offspring of affected parents, 11.92 in singleton siblings, 39.22 in multiplex families and 21.88 in twins; the calculated risk for monozygotic twins was 32.33. Type 1 diabetes in offspring was associated with 13 diseases in parents, including Addison's disease (SIR 2.41), asthma (1.38), coeliac disease (2.73), Graves' disease/hyperthyroidism (1.86), Hashimoto disease/hypothyroidism (2.35), pernicious anaemia (3.09), primary biliary cirrhosis (3.63), rheumatoid arthritis (2.12), sarcoidosis (1.62), systemic lupus erythematosus (2.04), ulcerative colitis (1.23) and Wegener's granulomatosis (2.12).


CONCLUSIONS
The concordant familial risks for type 1 diabetes were high and the calculated risk for multiplex families and monozygotic twins may be explained by epistatic gene x gene or gene x environment interactions. Familial associations with several autoimmune and related diseases suggest genetic sharing and challenge to gene identification.
Hemminki
K
K
Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 580, 69120, Heidelberg, Germany. k.hemminki@dkfz.de
Li
X
X
Sundquist
J
J
Sundquist
K
K
D000293:Adolescent; D001327:Autoimmune Diseases / Q000453:epidemiology / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000453:epidemiology / Q000235:genetics*; D005190:Family; D005220:Fathers; D005260:Female; D055106:Genome-Wide Association Study; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D007223:Infant; D008297:Male; D009035:Mothers; D012042:Registries; D012727:Sex Characteristics; D013548:Sweden; D014430:Twins, Monozygotic; D055815:Young Adult