Familial risks for amyotrophic lateral sclerosis and autoimmune diseases.
Population-level familial risks are not available for amyotrophic lateral sclerosis (ALS), and a few studies have analyzed familial association of ALS with other diseases. We used the Swedish Multigeneration Register to identify family members and link them to the Hospital Discharge Register to calculate standardized incidence ratios (SIRs) for familial association in ALS and 33 autoimmune diseases. Among 4,970 ALS patients, familial SIR for offspring of affected parents was 4.71, for singleton siblings, it was 29.83, and for members of multiplex families, it was 1,100; 1.1% of the offspring had an affected parent, and 2.2% an affected sibling. The high risks among siblings without affected parents may suggest recessive inheritance. The SIR for spouse correlation for ALS was 2.35 which may imply the influence of yet unknown environmental factors in ALS susceptibility. ALS associated with Behcet disease, multiple sclerosis, ulcerative colitis, and Wegener granulomatosis; however, chance associations cannot be excluded. In this first population level family study on ALS and 33 autoimmune and related conditions, we found high familial risks depending on the proband. These findings should guide future genomic studies. The high spouse correlation will be a challenge to environmental epidemiology of ALS.
Hemminki
Kari
K
Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 580, D-69120, Heidelberg, Germany. k.hemminki@dkfz.de
Li
Xinjun
X
Sundquist
Jan
J
Sundquist
Kristina
K
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics*; D001327:Autoimmune Diseases / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D005190:Family; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D012042:Registries; D012307:Risk Factors; D013548:Sweden; D055815:Young Adult