Causal relationship between feelings and cognitive decline: An univariable and multivariable Mendelian randomization study

Table 1 Detailed information on data sources

Trait	n	Case	Control	ID	Cohort(s)	Population
Intelligence	269867			ebi-a-GCST006250	Meta-analysis of 14 cohorts	European
Happiness	152348			ukb-b-4062	UK Biobank	European
Fed-up feelings	453071	184258	268813	ukb-b-19809	UK Biobank	European
Worrier/anxious feelings	450765	255812	194953	ukb-b-6519	UK Biobank	European
Guilty feelings	450704	129383	321321	ukb-b-10169	UK Biobank	European
Nervous feelings	450700	106635	344065	ukb-b-20544	UK Biobank	European
Sensitivity/hurt feelings	449419	249799	199620	ukb-b-9981	UK Biobank	European
Miserableness	454982	195435	259547	ukb-b-18994	UK Biobank	European
Loneliness, isolation	455364	82436	372928	ukb-b-8476	UK Biobank	European

Table 2 Sensitivity analysis of feelings and cognition

Risk factors	Pleiotropy test			Heterogeneity test
	Intercept	P value1	P value2 (distortion)	Cochran’s Q	P Value
Fed-up feelings	0.007	0.428	0.387	61.73	< 0.001
Worrier/anxious feelings	0.026	0.018	0.012	87.97	< 0.001
Guilty feelings	0.0003	0.761	0.257	47.46	< 0.001
Nervous feelings	-0.006	0.242	0.317	46.51	< 0.001
Sensitivity/hurt feelings	-0.002	0.816	NA	23.06	0.017
Miserableness	0.018	0.246	0.553	28.44	< 0.001
Loneliness, isolation	0.003	0.946	NA	14.31	< 0.001

¹P values assessing pleiotropy were obtained using the MR-Egger test, and a P value < 0.05 suggests a potential pleiotropic effect.

²P values for distortion were obtained through the MR-PRESSO test, where a P value < 0.05 indicates a significant distinction between estimates before and after removing outliers. Notably, the distortion test P value was not applicable for loneliness/isolation and sensitivity/hurt feelings analysis.