Mortality among family members of patients with amyotrophic lateral sclerosis – a Swedish register-based study

Figures & data

Table 1 Characteristics of the partners, parents and siblings of persons with and without ALS.

	Partners of				Parents of				Siblings of
	ALS-free individuals (N = 4,085,294)		ALS patients (N = 2,650)		ALS-free individuals (N = 5,420,670)		ALS patients (N = 4,512)		ALS-free individuals (N = 4,954,186)		ALS patients (N = 4,542)
Characteristics	N	%	N	%	N	%	N	%	N	%	N	%
Sex
Men	2,103,629	51.49	1,083	40.87	2,629,210	48.50	2,062	45.71	2,537,794	51.24	2,346	51.65
Women	1,981,665	48.51	1,567	59.13	2,791,460	51.50	2,449	54.29	2,411,419	48.76	2,196	48.35
Socio-economic status
Blue-collar	1,920,055	47.00	1,362	51.40	2,024,148	37.34	879	19.49	2,371,072	47.95	2,418	53.24
White-collar	1,036,353	25.37	567	21.40	915,068	16.88	372	8.25	1,131,145	22.87	870	19.15
Farmers	97,030	2.38	69	2.60	132,015	2.44	100	2.22	104,460	2.11	160	3.52
Self-employed/Other	778,108	19.05	417	15.74	1,337,771	24.68	1,966	43.58	878,348	17.76	706	15.54
Unemployed	244,136	5.98	233	8.79	956,002	17.64	1164	25.80	388,748	7.86	379	8.34
Unknown	9,612	0.24	2	0.08	55,666	1.03	30	0.67	71,413	1.44	9	0.20
Country of birth
Sweden	3,798,856	92.99	2,516	94.94	4,877,500	89.98	4,319	95.74	4,864,979	98.38	4,530	99.74
Denmark, Finland, Iceland or Norway	103,389	2.53	76	2.87	256,294	4.73	103	2.28	35,598	0.72	8	0.18
Other	181,784	4.45	56	2.11	259,858	4.79	60	1.33	42,760	0.86	3	0.07
Unknown	1,265	0.03	2	0.08	27,018	0.50	29	0.64	1,849	0.04	1	0.02

Table 2 Mortality among partners of ALS patients after ALS diagnosis in the proband patient, compared with partners of ALS-free individuals, a nationwide cohort study of Sweden, 1961–2013.

Cause of death	Partners		Male partners		Female partners
	No. of deaths	HR (95% CI)	No. of deaths	HR (95% CI)	No. of deaths	HR (95% CI)
All-cause mortality	357,313	0.98 (0.85–1.12)	255,199	1.03 (0.86–1.23)	102,114	0.91 (0.72–1.14)
Cause-specific mortality
Infectious and  parasitic diseases	4,014	1.41 (0.53–3.77)	2,870	2.40 (0.90–6.44)*	1,144	NA
Neoplasms	141,689	0.84 (0.67–1.06)	86,940	0.94 (0.69–1.28)	54,749	0.75 (0.53–1.06)
Diseases of the blood	708	NA	484	NA	224	NA
Endocrine, nutritional and  metabolic disease	7,940	0.83 (0.31–2.22)	5,942	1.29 (0.48–3.44)	1,998	NA
Psychiatric disorders,  excluding dementias	4,657	0.82 (0.12–5.83)	3,816	1.31 (0.18–9.32)	841	NA
Diseases of the nervous system, excluding ALS  and dementias	5,521	0.84 (0.27–2.60)	3,569	0.51 (0.07–3.63)	1,952	1.25 (0.31–5.01)
Dementias	6,203	1.17 (0.58–2.37)	4,605	0.98 (0.37–2.63)	1,598	1.49 (0.54–4.12)
Diseases of the  circulatory system	107,856	0.95 (0.74–1.22)	88,771	0.93 (0.69–1.25)	19,085	1.02 (0.65–1.59)
Diseases of the  respiratory system	15,588	1.16 (0.69–1.97)	10,735	1.15 (0.57–2.31)	4,853	1.18 (0.53–2.64)
Diseases of the  digestive system	13,315	0.62 (0.23–1.66)	9,763	0.56 (0.14–2.24)	3,552	0.69 (0.17–2.78)
Disease of the skin and  subcutaneous tissue	224	NA	165	NA	59	NA
Diseases of the  musculoskeletal system	1,413	2.07 (0.52–8.31)	727	2.82 (0.40–20.09)	686	1.65 (0.23–11.74)
Diseases of the  genitourinary system	2,251	NA	1,743	NA	508	NA
Unclassified	4,366	1.81 (0.75–4.36)	3,186	1.91 (0.61–5.96)	1,180	1.67 (0.42–6.74)
External causes	38,611	2.14 (1.35–3.41)***	29,616	2.10 (1.16–3.80)**	8,995	2.21 (1.05–4.65)**
- Suicide	15,721	2.44 (1.09–5.44)**	11,773	2.70 (1.01–7.23)**	3,948	2.02 (0.50–8.09)
- Accidents	17,134	2.09 (1.12–3.90)**	13,810	2.24 (1.06–4.72)**	3,324	1.82 (0.59–5.67)
- External all other	5756	1.74 (0.43–6.98)	4,033	NA	1,723	3.81 (0.95–15.33)*

HR: hazard ratio; CI: confidence interval; estimates were adjusted for attained age, sex, socio-economic status, and country of birth of the partners as well as age and sex of the index person. NA: not available due to zero deaths among partners of ALS patients. ***p < 0.001; **p < 0.05; *p < 0.1. Bold font indicates associations with two-sided p < 0.05.

Table 3 Mortality among parents of ALS patients, compared with parents of ALS-free individuals, a nationwide cohort study of Sweden, 1961–2013.

Cause of death	Parents		Fathers		Mothers
	No. of deaths	HR (95% CI)	No. of deaths	HR (95% CI)	No. of deaths	HR (95% CI)
All-cause mortality	2,199,548	1.03 (1.00–1.07)**	1,169,906	1.00 (0.95–1.05)	1,029,642	1.07 (1.02–1.12)***
Cause-specific mortality
Infectious and parasitic  diseases	24,468	1.02 (0.74–1.41)	11,689	1.28 (0.82–1.99)	12,779	0.84 (0.53–1.33)
Neoplasms	574,303	0.90 (0.83–0.97)***	300,354	0.88 (0.79–0.97)**	273,949	0.92 (0.83–1.02)
Diseases of the blood	5,451	0.79 (0.38–1.67)	2,467	1.44 (0.60–3.49)	2,984	0.37 (0.09–1.50)
Endocrine, nutritional and  metabolic disease	45,230	0.94 (0.74–1.19)	21,602	0.65 (0.41–1.01)*	23,628	1.14 (0.86–1.51)
Psychiatric disorders,  excluding dementias	12,318	1.29 (0.79–2.12)	8,504	1.10 (0.55–2.22)	3,814	1.56 (0.78–3.13)
Diseases of the nervous  system, excluding ALS  and dementias	21,690	1.32 (0.95–1.82)*	11,169	1.20 (0.73–1.96)	10,521	1.42 (0.93–2.18)
Dementias	81,177	1.35 (1.17–1.56)***	26,842	1.35 (1.03–1.78)**	54,335	1.35 (1.14–1.61)***
Diseases of the circulatory  system	983,554	1.06 (1.02–1.11)***	536,465	1.05 (0.98–1.12)	447,089	1.08 (1.01–1.15)**
Diseases of the respiratory  system	132,851	1.14 (1.01–1.29)**	70,890	0.98 (0.81–1.17)	61,961	1.32 (1.13–1.55)***
Diseases of the digestive  system	68,101	0.90 (0.74–1.10)	36,188	0.75 (0.55–1.04)*	31,913	1.04 (0.80–1.35)
Disease of the skin and  subcutaneous tissue	2,519	2.29 (1.26–4.18)***	930	3.42 (1.41–8.31)***	1,589	1.79 (0.79–4.03)
Diseases of the  musculoskeletal system	10,569	1.23 (0.81–1.88)	3,346	0.78 (0.29–2.08)	7,223	1.42 (0.89–2.25)
Diseases of the  genitourinary system	26,753	1.03 (0.78–1.35)	14,654	1.00 (0.68–1.47)	12,099	1.06 (0.71–1.57)
Unclassified	32,821	1.30 (1.03–1.63)**	12,353	1.61 (1.09–2.37)**	20,468	1.16 (0.87–1.56)
External causes	107,082	0.98 (0.81–1.17)	68,461	1.03 (0.82–1.31)	38,621	0.90 (0.68–1.19)
- Suicide	32,160	0.77 (0.50–1.18)	22,061	0.85 (0.51–1.42)	10,099	0.61 (0.28–1.37)
- Accidents	61,095	1.03 (0.83–1.28)	37,904	1.06 (0.79–1.42)	23,191	1.00 (0.73–1.37)
- External all other	13,827	1.06 (0.62–1.83)	8,496	1.34 (0.69–2.58)	5,331	0.72 (0.27–1.93)

HR: hazard ratio; CI: confidence interval; estimates were adjusted for attained age, sex, socio-economic status, and country of birth of the parents as well as age and sex of the index person. NA: not available due to zero deaths among parents of ALS patients. ***p < 0.001; ** p < 0.05; *p < 0.1. Bold font indicates associations with two-sided p < 0.05.

Table 4 Mortality among full siblings of ALS patients, compared with full siblings of ALS-free individuals, a nationwide cohort study of Sweden, 1961–2013.

Cause of death	Siblings		Brothers		Sisters
	No. of deaths	HR (95% CI)	No. of deaths	HR (95% CI)	No. of deaths	HR (95% CI)
All-cause mortality	300,016	1.06 (0.98–1.15)	184,999	1.11 (1.00–1.22)**	115,017	1.00 (0.87–1.14)
Cause-specific mortality
Infectious and parasitic  diseases	3,747	1.16 (0.58–2.32)	2,270	1.47 (0.66–3.28)	1,477	0.70 (0.17–2.84)
Neoplasms	103,535	0.94 (0.82–1.08)	52,011	1.02 (0.85–1.22)	51,524	0.86 (0.70–1.05)
Diseases of the blood	669	NA	380	NA	289	NA
Endocrine, nutritional  and metabolic disease	7,397	1.38 (0.89–2.14)	4,865	1.54 (0.92–2.55)*	2,532	1.06 (0.44–2.54)
Psychiatric disorders,  excluding dementias	4,872	1.15 (0.62–2.14)	3,916	1.00 (0.48–2.10)	956	1.77 (0.57–5.51)
Diseases of the nervous  system, excluding ALS  and dementias	6,843	1.37 (0.83–2.28)	3,935	1.14 (0.54–2.39)	2,908	1.68 (0.83–3.37)
Dementias	2,872	2.30 (1.44–3.67)***	1,430	2.64 (1.45–4.82)***	1,442	1.91 (0.91–4.03)*
Diseases of the  circulatory system	64,912	0.97 (0.82–1.14)	46,363	0.90 (0.74–1.10)	18,549	1.13 (0.85–1.50)
Diseases of the  respiratory system	11,683	1.29 (0.92–1.82)	6,342	1.35 (0.86–2.13)	5,341	1.21 (0.72–2.05)
Diseases of the digestive  system	10,559	1.74 (1.27–2.38)***	6,973	1.96 (1.36–2.82)***	3,586	1.31 (0.70–2.45)
Disease of the skin and  subcutaneous tissue	181	4.37 (1.05–18.18)**	106	8.28 (1.98–34.73)***	75	NA
Diseases of the  musculoskeletal system	1,263	1.12 (0.36–3.49)	469	1.96 (0.49–7.90)	794	0.60 (0.08–4.30)
Diseases of the  genitourinary system	1,475	0.63 (0.16–2.54)	858	1.01 (0.25–4.05)	617	NA
Unclassified	5,524	1.29 (0.69–2.40)	3,574	0.95 (0.39–2.28)	1,950	2.02 (0.84–4.88)
External causes	47,581	1.14 (0.89–1.46)	35,287	1.25 (0.95–1.64)	12,294	0.85 (0.48–1.49)
- Suicide	17,536	1.39 (0.97–1.99)*	12,756	1.50 (1.01–2.25)**	4,780	1.06 (0.47–2.36)
- Accidents	23,391	1.07 (0.73–1.56)	17,812	1.19 (0.79–1.80)	5,579	0.67 (0.25–1.78)
- External all other	6,654	0.73 (0.33–1.64)	4,719	0.70 (0.26–1.87)	1,935	0.81 (0.20–3.23)

HR: hazard ratio; CI: confidence interval; estimates were adjusted for attained age, sex, socio-economic status, and country of birth of the siblings as well as age and sex of the index person. NA: not available due to zero deaths among siblings of ALS patients. ***p < 0.001; ** p < 0.05; *p < 0.1. Bold font indicates associations with two-sided p < 0.05.

Data availability statement

The data are not publicly available due to privacy or ethical restrictions.