Associations between autoimmune diseases and amyotrophic lateral sclerosis: a register-based study

Figures & data

Table 1 Characteristics of patients with amyotrophic lateral sclerosis (ALS), their matched controls, and the respective relatives of both groups, a nested case-control study in Sweden, 1990–2013.

Characteristics	Patients with ALS	Controls	Siblings of ALS patients	Siblings of controls	Children of ALS patients	Children of controls
Total	3561	35,610	5013	48,751	6589	65,980
Sex, n (%)
Male	2136 (59.98)	21,360 (59.98)	2625 (52.36)	24,954 (51.19)	3378 (51.27)	33,755 (51.16)
Female	1425 (40.02)	14,250 (40.02)	2388 (47.64)	23,797 (48.81)	3211 (48.73)	32,225 (48.84)
Mean age at index date or cohort entry (SD)*	60.58 (11.22)	60.58 (11.21)	41.40 (10.17)	41.41 (10.20)	17.17 (9.74)	16.98 (9.95)
Education, n (%)
≤9 years	1164 (32.69)	11,683 (32.81)	1566 (31.24)	15,450 (31.69)	529 (8.03)	5069 (7.68)
10–12 years	1514 (42.52)	14,762 (41.45)	2232 (44.52)	21,255 (43.60)	3069 (46.58)	30,181 (45.74)
University+	839 (23.56)	8911 (25.02)	1181 (23.56)	11,682 (23.96)	2583 (39.20)	26,178 (39.68)
Missing	44 (1.24)	254 (0.71)	34 (0.68)	364 (0.75)	408 (6.19)	4552 (6.90)
Socioeconomic status, n (%)
Blue-collar	1253 (35.19)	12,770 (35.86)	2063 (41.15)	19,704 (40.42)	1772 (26.89)	17,305 (26.23)
White-collar	1508 (42.35)	15,084 (42.36)	1784 (35.59)	18,390 (37.72)	1006 (15.27)	10,277 (15.58)
Farmers/self-employed	240 (6.74)	2418 (6.79)	340 (6.78)	3122 (6.40)	62 (0.94)	761 (1.15)
Others	110 (3.09)	1185 (3.33)	204 (4.07)	1819 (3.73)	404 (6.13)	3931 (5.96)
Missing	450 (12.64)	4153 (11.66)	622 (12.41)	5716 (11.72)	3345 (50.77)	33,706 (51.09)

*Mean age at index date or cohort entry (SD): mean age at index date for patients with ALS and controls, and mean age at cohort entry for siblings and children of ALS patients and siblings and children of controls.

Table 2 Association of autoimmune diseases with the risk of amyotrophic lateral sclerosis (ALS), adjusted for age, sex, county of birth, education, and socioeconomic status, a nested case-control study in Sweden, 1990–2013.

Autoimmune diseases	Patients with ALS, n (%)	Controls, n (%)	OR (95% CI)^a	FDR^b
Any autoimmune disease	500 (14.04)	3743 (10.51)	1.47 (1.31–1.64)	5.041E–11
Myasthenia gravis	17 (0.48)	11 (0.03)	17.2 (7.66–38.6)	5.041E–11
Polymyositis/dermatomyositis	17 (0.48)	15 (0.04)	10.2 (4.82–21.4)	4.838E–09
Guillain-Barre syndrome	46 (1.29)	74 (0.21)	8.09 (5.24–12.5)	7.382E–20
Type 1 diabetes, any	87 (2.44)	844 (2.37)	1.01 (0.79–1.29)	0.944
Type 1 diabetes, <30y	14 (0.39)	56 (0.16)	2.44 (1.26–4.74)	0.024
Multiple sclerosis	25 (0.70)	107 (0.30)	2.28 (1.37–3.77)	0.004
Hypothyreosis	64 (1.80)	419 (1.18)	1.49 (1.11–2.01)	0.024
Ankylosing spondylitis	30 (0.84)	213 (0.60)	1.59 (1.04–2.44)	0.074
Polymyalgia rheumatica	19 (0.53)	143 (0.40)	1.59 (0.97–2.60)	0.124
Temporal arteritis	12 (0.34)	79 (0.22)	1.61 (0.85–3.07)	0.237
Adult rheumatoid arthritis	79 (1.96)	689 (1.93)	1.27 (0.99–1.64)	0.124
Crohn’s disease	19 (0.53)	171 (0.48)	1.25 (0.76–2.06)	0.512
Sarcoidosis	13 (0.37)	107 (0.30)	1.34 (0.75–2.41)	0.486
Sjögren’s syndrome	11 (0.31)	92 (0.26)	1.18 (0.59–2.36)	0.775
Ulcerative colitis	31 (0.87)	293 (0.82)	1.12 (0.75–1.66)	0.737
Hyperthyroidism	26 (0.73)	270 (0.76)	1.06 (0.69–1.63)	0.887
Psoriasis	54 (1.52)	546 (1.53)	1.03 (0.76–1.39)	0.899

^aOR: Odds ratio; CI: confidence interval. Bold numbers indicate significant differences at p < 0.05. ^bFDR: false discovery rate. Bold numbers indicate significant differences at FDR < 0.05.

Table 3 Association of autoimmune diseases with the risk of amyotrophic lateral sclerosis (ALS), by years before diagnosis.

Autoimmune diseases	Years prior to diagnosis
	≥6	2–5	0–1
Any autoimmune diseases
No. of cases/controls	263/2594	113/891	124/258
OR (95% CI)^a	1.10 (0.95–1.27)	1.40 (1.13–1.72)	5.11 (4.05–6.46)
Myasthenia gravis
No. of cases/controls	2/7	3/3	12/1
OR (95% CI)^a	3.64 (0.70–18.8)	9.95 (2.01–49.3)	105 (13.6–808)
Polymyositis/dermatomyositis
No. of cases/controls	2/11	5/2	10/2
OR (95% CI)^a	1.77 (0.39–8.12)	18.4 (3.36–100)	76.0 (9.61–601)
Guillain-Barre syndrome
No. of cases/controls	14/64	8/5	24/5
OR (95% CI)^a	2.52 (1.25–5.08)	21.6 (5.58–83.6)	40.4 (15.3–107)
Type 1 diabetes, <30y
No. of cases/controls	14/55	0/1	0/0
OR (95% CI)^a	2.44 (1.26–4.74)	–	–
Multiple sclerosis
No. of cases/controls	12/89	5/16	8/2
OR (95% CI)^a	1.17 (0.56–2.44)	3.04 (0.98–9.44)	32.8 (6.81–158)
Hypothyreosis
No. of cases/controls	15/193	15/168	34/58
OR (95% CI)^a	0.81 (0.46–1.44)	0.83 (0.46–1.50)	5.14 (3.24–8.15)
Ankylosing spondylitis
No. of cases/controls	23/190	5/20	2/3
OR (95% CI)^a	1.30 (0.79–2.13)	3.30 (1.17–9.30)	6.42 (1.07–38.4)

^aOR: Odds ratio; CI: confidence interval. All results adjusted for age, sex, county of birth, education, and socioeconomic status. Bold numbers indicate significant differences at P < 0.05.

Table 4 Risk of autoimmune diseases among siblings of patients with amyotrophic lateral sclerosis (ALS), as compared to siblings of ALS-free controls, adjusted for age, sex, county of birth, education, and socioeconomic status.

Autoimmune diseases	Siblings of patients with ALS, n (%)	Siblings of controls, n (%)	HR (95% CI)^a
Any autoimmune disease	642 (12.81)	6434 (13.2)	0.91 (0.91–1.08)
Myasthenia gravis	2 (0.04)	18 (0.04)	1.29 (0.29–5.64)
Polymyositis/dermatomyositis	6 (0.12)	25 (0.05)	2.17 (0.83–5.72)
Guillain-Barre syndrome	3 (0.06)	57 (0.12)	0.60 (0.19–1.94)
Type 1 diabetes, any	119 (2.37)	1232 (2.53)	0.96 (0.78–1.17)
Type 1 diabetes, <30y	1 (0.02)	8 (0.02)	9.46 (0.59–152)
Multiple sclerosis	12 (0.24)	137 (0.28)	0.85 (0.44–1.61)
Hypothyreosis	147 (2.93)	1200 (2.46)	1.30 (1.09–1.56)
Ankylosing spondylitis	16 (0.32)	143 (0.29)	1.00 (0.57–1.78)
Polymyalgia rheumatica	48 (0.96)	353 (0.72)	1.46 (1.06–2.00)
Temporal arteritis	17 (0.34)	150 (0.31)	1.21 (0.72–2.03)
Adult rheumatoid arthritis	71 (1.42)	819 (1.68)	0.86 (0.66–1.11)
Crohn’s disease	16 (0.32)	187 (0.38)	0.85 (0.49–1.46)
Sarcoidosis	14 (0.28)	140 (0.29)	0.97 (0.53–1.73)
Sjögren’s syndrome	26 (0.52)	204 (0.42)	1.17 (0.75–1.83)
Ulcerative colitis	26 (0.52)	387 (0.79)	0.70 (0.46–1.06)
Hyperthyroidism	51 (1.02)	498 (1.02)	0.92 (0.67–1.28)
Psoriasis	111 (2.21)	1244 (2.55)	0.92 (0.76–1.13)

^aHR: Hazad ratio; CI: confidence interval. Bold numbers indicate significant differences at p < 0.05.

Table 5 Risk of autoimmune diseases among children of patients with amyotrophic lateral sclerosis (ALS), as compared to siblings of ALS-free controls, adjusted for age, sex, county of birth, education, and socioeconomic status.

Autoimmune diseases	Children of patients with ALS, n (%)	Children of Controls, n (%)	HR (95% CI)^a
Any autoimmune disease	491 (7.45)	4670 (7.08)	1.03 (0.91–1.17)
Myasthenia gravis	1 (0.02)	9 (0.01)	5.02 (0.45–55.4)
Polymyositis/dermatomyositis	2 (0.03)	9 (0.01)	–
Guillain-Barre syndrome	0 (0.00)	26 (0.04)	–
Type 1 diabetes, any	47 (0.71)	466 (0.71)	1.06 (0.69–1.63)
Type 1 diabetes, <30y	23 (0.35)	220 (0.33)	0.24 (0.03–1.72)
Multiple sclerosis	14 (0.21)	174 (0.26)	0.67 (0.33–1.37)
Hypothyreosis	72 (1.09)	707 (1.07)	0.97 (0.68–1.38)
Ankylosing spondylitis	14 (0.21)	144 (0.22)	1.00 (0.51–1.99)
Polymyalgia rheumatica	4 (0.06)	20 (0.03)	2.47 (0.83–7.36)
Temporal arteritis	1 (0.02)	14 (0.02)	–
Adult rheumatoid arthritis	40 (0.61)	341 (0.52)	1.21 (0.81–1.80)
Crohn’s disease	32 (0.49)	286 (0.43)	1.08 (0.63–1.84)
Sarcoidosis	17 (0.26)	157 (0.24)	0.71 (0.34–1.45)
Sjögren’s syndrome	8 (0.12)	56 (0.08)	1.19 (0.47–3.00)
Ulcerative colitis	48 (0.73)	509 (0.77)	1.11 (0.76–1.62)
Hyperthyroidism	53 (0.80)	377 (0.57)	1.45 (1.02–2.06)
Psoriasis	117 (1.78)	1024 (1.55)	1.10 (0.85–1.42)

^a HR: Hazad ratio; CI: confidence interval. Bold numbers indicate significant differences at p < 0.05.