Testing a method to improve predictions of disease and mortality risk in western lowland gorillas (gorilla gorilla gorilla) using allostatic load

Figures & data

Figure 1. The full list of available biomarkers was refined into a final list of biomarkers to include in an allostatic load index using a combination of forward stepwise regression and independent biomarker associations. Biomarkers with a tolerance statistic >0.20 that associated independently with fewer than 25% of project variables were removed from the allostatic load index; those that met only one criterion also were considered for removal.

Table 1. High-risk quartile boundaries for biomarkers included in allostatic load indices combined using a one-tailed quartile approach and a multi-method, split quartile approach (top and bottom 12.5%) for cortisol.

Sample	Location	n	Albumin (g/dL)	CRH (pg/mL)	Cortisol (µg/dL)		Creatinine (mg/dL)	HOMA-IR	IL-6 (pg/mL)	TNF-α (pg/mL)
					one-tailed quartile approach	multi-method approach
Pooled Sample 1 (each zoo scored independently prior to pooling)	Columbus Zoo	27	M ≤ 3.65 F ≤ 3.08	≥4.35	M ≥ 11.10 F ≥ 19.55	M ≤ 8.98, ≥ 11.78 F ≤ 9.15, ≥ 25.94	≥1.80	≥2.11	M ≥ 3.48 F ≥ 14.38	≥0.98
	Louisville Zoo	22	≤3.30	M ≥ 6.10 F ≥ 5.57	M ≥ 14.50 F ≥ 23.80	M ≤ 5.83, ≥ 15.85 F ≤ 7.55, ≥ 29.23	≥1.26	≥1.45	M ≥ 13.42 F ≥ 6.84	≥0.53
	Omaha’s Henry Doorly Zoo	14	M ≤ 4.20 F ≤ 3.45	≥5.61	M ≥ 10.95 F ≥ 19.68	M ≤ 7.96, ≥ 11.22 F ≤ 10.31, ≥ 20.09	M ≥ 1.01 F ≥ 1.68	≥0.55	≥5.24	M ≥ 0.26 F ≥ 0.62
Pooled Sample 2 (all zoos pooled prior to scoring)	All	63	M ≤ 3.60 F ≤ 3.20	≥5.75	M ≥ 11.36 F ≥ 20.50	M ≤ 7.26, ≥ 14.31 F ≤ 8.60, ≥ 27.05	≥1.61	M ≥ 1.14 F ≥ 2.02	≥8.02	≥0.56

Pooled Sample 1 estimated allostatic load at each zoo independently prior to combining scores into a single sample, while Pooled Sample 2 combined biomarker values prior to estimating allostatic load.

Of the biomarkers included, there is evidence to demonstrate that cortisol quartile boundaries may need split between the lowest and highest values in the distribution and so a split quartile was used for the multi-method approach; traditional one-tailed quartile boundaries were used for all other biomarkers.

Table 2. Means, standard deviations, and ranges for each allostatic load index tested in western lowland gorillas (n = 63), as well as associations of allostatic load with age (linear regression) and sex (t-test).

				Age		Sex
ALI	$\overline{x}$	SD	Range	p Value	R^2	t	df	p Value
New ALIs
PS1 ALQ	2.03	1.69	0-6	0.014	0.090	0.600	61	0.551
PS2 ALQ	1.84	1.61	0-6	0.034	0.073	0.430	61	0.669
PS1 ALM	2.32	1.65	0-6	0.010	0.103	0.527	61	0.600
PS1 ALM	1.86	1.54	0-6	0.014	0.095	0.371	61	0.712
Original ALIs
PS1 ALQ	1.86	1.51	0-5	0.004	0.126	−0.784	61	0.436
PS2 ALQ	1.81	1.46	0-5	0.007	0.115	−0.393	61	0.696
PS1 ALM	1.92	1.50	0-5	0.002	0.149	−0.607	61	0.546
PS1 ALM	1.83	1.40	0-5	0.002	0.148	−0.496	61	0.622

ALI, allostatic load index; ALM, allostatic load index constructed with a multi-method approach; ALQ, allostatic load index constructed with traditional one-tailed quartiles; PS1, pooled sample 1; PS2, pooled sample 2.

Figure 2. Relative risk of developing at least one chronic condition in western lowland gorillas for each allostatic load index tested. Error bars represent 95% confidence intervals. ALI: allostatic load index; ALM: allostatic load index constructed with a multi-method approach; ALQ: allostatic load index constructed with traditional one-tailed quartiles; PS1: pooled sample 1; PS2: pooled sample 2.

Table 3 Risk of all-cause morbidity in western lowland gorillas (n = 63) was analyzed using binomial generalized linear models (GLMs) with logit links for a baseline model with age and sex only, a model with each allostatic load index only, and a full model with allostatic load and significant variables from the baseline model.

		Allostatic Load			Age			Sex
	ALI	p Value	OR	95% CI	p Value	OR	95% CI	p Value	OR	95% CI	AICc
Baseline					0.0002	1.15	1.08–1.25	0.001	10.78	2.78–54.49	61.7
New ALIs	PS1 ALQ	0.080	1.33	0.98–1.88							87.4
		0.697	1.08	0.73–1.63	0.0003	1.15	1.07–1.25	0.002	10.51	2.70–55.17	63.8
	PS2 ALQ	0.573	1.10	0.80–1.52							90.4
		0.471	0.85	0.53–1.32	0.0001	1.15	1.08–1.26	0.001	11.59	2.91–61.59	63.5
	PS1 ALM	0.073	1.35	0.99–1.92							87.3
		0.718	1.08	0.72–1.63	0.0003	1.15	1.07–1.25	0.002	10.49	2.70–53.13	63.9
	PS2 ALM	0.509	1.12	0.81–1.58							90.3
		0.406	0.82	0.50–1.30	0.0001	1.16	1.08–1.26	0.001	12.01	2.97–66.05	63.3
Original ALIs	PS1 ALQ	0.068	1.39	0.99–2.02							87.2
		0.251	1.32	0.84–2.18	0.0004	1.15	1.07–1.25	0.001	12.51	3.08–68.14	62.6
	PS2 ALQ	0.641	1.09	0.77–1.55							90.5
		0.498	0.84	0.50–1.37	0.0001	1.15	1.08–1.26	0.002	10.66	2.74–54.12	63.5
	PS1 ALM	0.049	1.44	1.01–2.12							86.6
		0.305	1.28	0.81–2.13	0.0005	1.14	1.07–1.25	0.001	11.72	2.95–61.29	62.9
	PS2 ALM	0.570	1.11	0.77–1.62							90.4
		0.423	0.81	0.46–1.35	0.0001	1.16	1.08–1.26	0.002	10.80	2.75–55.43	63.3

The same analyses using the original allostatic load indices are provided for comparative purposes. The best fit model, as determined by the lowest AICc score, is the baseline model and is in bold.

Reference groups: all-cause morbidity, 1 = affected; sex: male; AICc: Akaike’s information criterion; adjusted for small sample size; ALI: allostatic load index; ALM: allostatic load index constructed with a multi-method approach; ALQ: allostatic load index constructed with traditional one-tailed quartiles; PS1: pooled sample 1; PS2: pooled sample 2.

Figure 3. Relative risk of developing cardiac disease in western lowland gorillas for each allostatic load index tested. Error bars represent 95% confidence intervals. ALI: allostatic load index; ALM: allostatic load index constructed with a multi-method approach; ALQ: allostatic load index constructed with traditional one-tailed quartiles; PS1: pooled sample 1; PS2: pooled sample 2.

Table 4. Risk of cardiac disease in western lowland gorillas (n = 63) was analyzed using binomial generalized linear models (GLMs) with logit links for a baseline model with age and sex only, a model with each allostatic load index only, and a full model with allostatic load and significant variables from the baseline model.

		Allostatic Load			Age			Sex
	ALI	p Value	OR	95% CI	p Value	OR	95% CI	p Value	OR	95% CI	AICc
Baseline					0.033	1.06	1.01–1.12	0.0003	10.72	3.21–44.59	73.6
New ALIs	PS1 ALQ	0.355	1.15	0.86–1.57							89.4
		0.951	1.01	0.69–1.47	0.043	1.06	1.00–1.12	0.0004	10.68	3.18–44.68	75.9
	PS2 ALQ	0.785	0.96	0.69–1.31							90.2
		0.245	0.78	0.50–1.16	0.019	1.07	1.01–1.13	0.0003	12.00	3.48–52.30	74.5
	PS1 ALM	0.402	1.14	0.84–1.56							89.5
		0.950	0.99	0.67–1.44	0.042	1.06	1.00–1.12	0.0003	10.77	3.20–45.19	75.9
	PS2 ALM	0.722	0.94	0.67–1.31							90.1
		0.177	0.73	0.44–1.12	0.016	1.07	1.02–1.14	0.0003	12.56	3.58–56.28	73.9
Original ALIs	PS1 ALQ	0.514	1.12	0.80–1.57							89.8
		0.630	1.11	0.73–1.71	0.056	1.05	1.00–1.11	0.0003	11.12	3.28–47.47	75.7
	PS2 ALQ	0.395	0.86	0.59–1.21							89.5
		0.129	0.70	0.43–1.09	0.013	1.07	1.02–1.13	0.0003	11.34	3.13–48.48	73.4
	PS1 ALM	0.478	1.13	0.81–1.60							89.7
		0.720	1.08	0.71–1.67	0.057	1.05	1.00–1.12	0.0003	10.92	3.24–46.06	75.8
	PS2 ALM	0.335	0.83	0.56–1.20							89.3
		0.082	0.64	0.36–1.03	0.010	1.08	1.02–1.15	0.0003	11.64	3.36–50.51	72.5

The same analyses using the original allostatic load indices are provided for comparative purposes. Models with better goodness of fit than the baseline model, as determined by the lowest AICc score, are in bold.

Reference groups: cardiac disease, 1 = affected; sex: male; AICc: Akaike’s information criterion, adjusted for small sample size; ALI: allostatic load index; ALM: allostatic load index constructed with a multi-method approach; ALQ: allostatic load index constructed with traditional one-tailed quartiles; PS1: pooled sample 1; PS2: pooled sample 2.

Figure 4. Relative risk of mortality in western lowland gorillas for each allostatic load index tested. Error bars represent 95% confidence intervals. ALI: allostatic load index; ALM: allostatic load index constructed with a multi-method approach; ALQ: allostatic load index constructed with traditional one-tailed quartiles; PS1: pooled sample 1; PS2: pooled sample 2.

Table 5. Risk of mortality in western lowland gorillas (n = 63) was analyzed using binomial generalized linear models (GLMs) with logit links for a baseline model with age and sex only, a model with each allostatic load index only, and a full model with allostatic load and significant variables from the baseline model.

		Allostatic Load			Age			Sex
	ALI	p Value	OR	95% CI	p Value	OR	95% CI	p Value	OR	95% CI	AICc
Baseline					0.003	1.07	1.03–1.13	0.872	0.91	0.28-2.94	76.3
New ALIs	PS1 ALQ	0.040	1.40	1.02–1.97							79.9
		0.195	1.26	0.89–1.82	0.010	1.07	1.02–1.12				74.6
	PS2 ALQ	0.015	1.56	1.11–2.28							77.8
		0.068	1.43	0.98–2.14	0.011	1.07	1.02–1.12				72.8
	PS1 ALM	0.135	1.28	0.93–1.79							82.1
		0.581	1.11	0.77–1.59	0.007	1.07	1.02–1.13				76.0
	PS2 ALM	0.031	1.49	1.05–2.20							79.3
		0.164	1.32	0.90–2.00	0.011	1.06	1.02–1.12				74.3
Original ALIs	PS1 ALQ	0.016	1.58	1.10–2.35							78.1
		0.126	1.37	0.92–2.08	0.016	1.06	1.01–1.12				73.9
	PS2 ALQ	0.009	1.71	1.17–2.63							76.6
		0.062	1.50	0.99–2.36	0.018	1.06	1.01–1.12				72.7
	PS1 ALM	0.061	1.42	0.99–2.10							80.7
		0.445	1.17	0.78–1.78	0.012	1.07	1.02–1.12				75.7
	PS2 ALM	0.031	1.56	1.06–2.40							79.3
		0.248	1.30	0.83–2.06	0.015	1.06	1.01–1.12				75.0

The same analyses using the original allostatic load indices are provided for comparative purposes. Each full model tested has a better goodness of fit than the baseline model, as determined by the lowest AICc score, and is in bold.

Reference groups: all-cause mortality, 1 = deceased; sex: male; AICc: Akaike’s information criterion, adjusted for small sample size; ALI: allostatic load index; ALM: allostatic load index constructed with a multi-method approach; ALQ: allostatic load index constructed with traditional one-tailed quartiles; PS1: pooled sample 1; PS2: pooled sample 2.

Data availability

Data supporting the findings of this study are available on request from the corresponding author, ANE. Individually identifiable data are not publicly available due to confidential agreements made between the corresponding author, ANE, and each cooperating zoological institution.