J Clin Med Res

Journal of Clinical Medicine Research, ISSN 1918-3003 print, 1918-3011 online, Open Access

Article copyright, the authors; Journal compilation copyright, J Clin Med Res and Elmer Press Inc

Journal website https://jocmr.elmerjournals.com

Original Article

Volume 16, Number 10, October 2024, pages 472-482

Bridging Three Years of Insights: Examining the Association Between Depression and Gallstone Disease

Figure 1. Flowchart on the stages of sample selection in this study. PHQ-9: Patient Health Questionnaire-9.

Figure 2. Independent effect of depression on the risk of gallstone disease using multivariable Mendelian randomization analysis. Model 1: independent effect of depression on gallstone disease after adjusting for cigarettes per day. Model 2: independent effect of depression on gallstone disease after adjusting for drinking. Model 3: independent effect of depression on gallstone disease after adjusting for education attainment (EA). Cigday: Heaviness of smoking was measured with cigarettes per day; OR: odds ratio; CI: confidence interval.

Figure 3. Results from the leave-one-out analysis which excluded each single nucleotide polymorphism to estimate the effects of depression-related traits on gallstone disease.

**Table 1.** Characteristics of the Participants With and Without Gallstone
	Non-gallstone (4,787)	Gallstone (516)	Statistics	P value
Data were presented as median (interquartile range) or n (%). ^at-test for continuous variables. ^bPearson’s Chi-squared test for categorical variables.
Age (years)	47 (33, 62)	57 (43, 69)	205.455	< 0.001^a
Smoker status			9.473	0.002^b
No	2,841 (59.35%)	270 (52.33%)
Yes	1,946 (40.65%)	246 (47.67%)
Alcohol intake			8.504	0.004^b
No	3,982 (83.18%)	455 (88.18%)
Yes	805 (16.82%)	61 (11.82%)
Gender			103.958	< 0.001^b
Male	2,429 (50.74%)	140 (27.13%)
Female	2,358 (49.26%)	376 (72.87%)
Race			29.312	< 0.001^b
Mexican American	502 (10.49%)	65 (12.60%)
Other Hispanic	441 (9.21%)	55 (10.66%)
Non-Hispanic White	1,725 (36.04%)	231 (44.77%)
Non-Hispanic Black	1,291 (26.97%)	96 (18.60%)
Another race	828 (17.30%)	69 (13.37%)
Marital status			27.823	< 0.001^b
Married/living with partner	2,813 (58.76%)	312 (60.47%)
Widowed/divorced/separated	959 (20.03%)	139 (26.94%)
Never married	1,014 (21.18%)	65 (12.60%)
Depressive symptoms			26.935	< 0.001^b
No	4,412 (92.17%)	441 (85.47%)
Yes	375 (7.83%)	75 (14.53%)
Body mass index			47.153	< 0.001^b
< 30	3,040 (63.51%)	248 (48.06%)
≥ 30	1,747 (36.49%)	268 (51.94%)
Physical activity (metabolic equivalent of task (min/week))			22.817	< 0.001^b
< 600	1,585 (33.11%)	225 (43.60%)
≥ 600	3,202 (66.89%)	291 (56.40%)
Education level			0.005	0.945^b
≤ high school	664 (13.87%)	71 (13.76%)
> high school	4,123 (86.13%)	445 (86.24%)
Poverty income ratio	2.46 (1.26, 4.62)	2.24 (1.28, 4.27)	115.317	< 0.001^a
Hypertension history			56.773	< 0.001^b
Without hypertension	3,157 (65.95%)	254 (49.22%)
With hypertension	1,630 (34.05%)	262 (50.78%)
Diabetes history			53.902	< 0.001^b
Without diabetes	4,095 (85.54%)	383 (74.22%)
With diabetes	567 (11.84%)	120 (23.26%)
Prediabetes	125 (2.61%)	13 (2.52%)

Table 1. Characteristics of the Participants With and Without Gallstone

Non-gallstone (4,787)

Gallstone (516)

Statistics

P value

Data were presented as median (interquartile range) or n (%). ^at-test for continuous variables. ^bPearson’s Chi-squared test for categorical variables.

Age (years)

47 (33, 62)

57 (43, 69)

205.455

< 0.001^a

Smoker status

9.473

0.002^b

2,841 (59.35%)

270 (52.33%)

Yes

1,946 (40.65%)

246 (47.67%)

Alcohol intake

8.504

0.004^b

3,982 (83.18%)

455 (88.18%)

Yes

805 (16.82%)

61 (11.82%)

Gender

103.958

< 0.001^b

Male

2,429 (50.74%)

140 (27.13%)

Female

2,358 (49.26%)

376 (72.87%)

Race

29.312

< 0.001^b

Mexican American

502 (10.49%)

65 (12.60%)

Other Hispanic

441 (9.21%)

55 (10.66%)

Non-Hispanic White

1,725 (36.04%)

231 (44.77%)

Non-Hispanic Black

1,291 (26.97%)

96 (18.60%)

Another race

828 (17.30%)

69 (13.37%)

Marital status

27.823

< 0.001^b

Married/living with partner

2,813 (58.76%)

312 (60.47%)

Widowed/divorced/separated

959 (20.03%)

139 (26.94%)

Never married

1,014 (21.18%)

65 (12.60%)

Depressive symptoms

26.935

< 0.001^b

4,412 (92.17%)

441 (85.47%)

Yes

375 (7.83%)

75 (14.53%)

Body mass index

47.153

< 0.001^b

< 30

3,040 (63.51%)

248 (48.06%)

≥ 30

1,747 (36.49%)

268 (51.94%)

Physical activity (metabolic equivalent of task (min/week))

22.817

< 0.001^b

< 600

1,585 (33.11%)

225 (43.60%)

≥ 600

3,202 (66.89%)

291 (56.40%)

Education level

0.005

0.945^b

≤ high school

664 (13.87%)

71 (13.76%)

> high school

4,123 (86.13%)

445 (86.24%)

Poverty income ratio

2.46 (1.26, 4.62)

2.24 (1.28, 4.27)

115.317

< 0.001^a

Hypertension history

56.773

< 0.001^b

Without hypertension

3,157 (65.95%)

254 (49.22%)

With hypertension

1,630 (34.05%)

262 (50.78%)

Diabetes history

53.902

< 0.001^b

Without diabetes

4,095 (85.54%)

383 (74.22%)

With diabetes

567 (11.84%)

120 (23.26%)

Prediabetes

125 (2.61%)

13 (2.52%)

**Table 2.** Association Between Depressive and Gallstone
	Gallstone, OR (95% CI), P value
Model 1 did not include any adjustments. Model 2 was adjusted for: gender, age, and race. Model 3 was adjusted for: gender, age, race, education level, marital status, poverty income ratio, body mass index, physical activity, smoking status, alcohol intake, diabetes history and hypertension history. OR: odds ratio; CI: confidence interval.
Without depressive symptoms	Reference	Reference	Reference
With depressive symptoms	2.001(1.523, 2.598), P < 0.001	1.928 (1.455, 2.528), P < 0.001	1.687 (1.261, 2.234), P < 0.001

Table 2. Association Between Depressive and Gallstone

Gallstone, OR (95% CI), P value

Model 1

Model 2

Model 3

Model 1 did not include any adjustments. Model 2 was adjusted for: gender, age, and race. Model 3 was adjusted for: gender, age, race, education level, marital status, poverty income ratio, body mass index, physical activity, smoking status, alcohol intake, diabetes history and hypertension history. OR: odds ratio; CI: confidence interval.

Without depressive symptoms

Reference

With depressive symptoms

2.001(1.523, 2.598), P < 0.001

1.928 (1.455, 2.528), P < 0.001

1.687 (1.261, 2.234), P < 0.001

**Table 3.** Causal Effects of Depression on Gallstone Disease
Exposure	Method	nSNP	OR (95% CI)	P value
MR: Mendelian randomization; SNP: single-nucleotide polymorphism; OR: odds ratio; CI: confidence interval; MR-PRESSO: Mendelian randomization pleiotropy residual sum and outlier.
Depression	Inverse variance weighted	87	1.164 (1.053 - 1.286)	0.003
	MR Egger	87	1.218 (0.684 - 2.169)	0.5
	Weighted median	87	1.142 (1.022 - 1.277)	0.019
	MR-PRESSO (3 outlier-corrected)	84	1.113 (1.020 - 1.215)	0.018
	Excluding palindromic SNPs	82	1.180 (1.064 - 1.308)	0.002
	Excluding pleiotropic SNPs	63	1.143 (1.023 - 1.278)	0.018

Table 3. Causal Effects of Depression on Gallstone Disease

Exposure

Method

nSNP

OR (95% CI)

P value

MR: Mendelian randomization; SNP: single-nucleotide polymorphism; OR: odds ratio; CI: confidence interval; MR-PRESSO: Mendelian randomization pleiotropy residual sum and outlier.

Depression

Inverse variance weighted

1.164 (1.053 - 1.286)

0.003

MR Egger

1.218 (0.684 - 2.169)

0.5

Weighted median

1.142 (1.022 - 1.277)

0.019

MR-PRESSO (3 outlier-corrected)

1.113 (1.020 - 1.215)

0.018

Excluding palindromic SNPs

1.180 (1.064 - 1.308)

0.002

Excluding pleiotropic SNPs

1.143 (1.023 - 1.278)

0.018