Table 3.

Linear regression analyses investigating the association between the GAD‐2 polygenic score and higher anxiety symptoms (GAD‐2) as a continuous measure in the Canadian and UKB samples, including participants with MS, anxiety, and no immune disease and healthy controls.

	Canada			UKB			Meta‐analyses
	All (N = 334)	Sex‐stratified		All (N = 45,195)	Sex‐stratified		All (N = 45,529)	Sex‐stratified
		Female	Male		Female	Male		Female	Male
GAD‐2 PGS	0.15 (0.09); 0.09	0.12 (0.10); 0.25	0.27 (0.21); 0.27	0.08 (0.01), <0.001	0.09 (0.01), <0.001	0.07 (0.01), <0.001	0.08 (0.01), <0.001, 0%	0.09 (0.01), <0.001, 0%	0.07 (.01), <0.001, 0%
Disease group: multiple sclerosis	1.64 (0.26), <0.001	1.64 (0.32); <0.001	1.51 (0.47); <0.001	0.56 (0.07), <0.001	0.62 (0.01), <0.001	0.42 (0.14), <0.01	0.63 (0.07), <0.001, 94% 1	0.62 (0.01), <0.001, 90.1%	0.51 (.13), <0.001, 79.3%
Disease group: anxiety	3.64 (0.29), <0.001	3.52 (0.36); <0.001	4.14 (0.59); <0.001	1.10 (0.02). <0.001	1.09 (0.02), <0.001	1.11 (0.02), <0.001	1.11 (0.02), <0.001, 98.7% 1	1.09 (0.02), <0.001, 97%	1.11 (0.02), <0.001, 96.2%

The outcome in all models is the GAD‐2 as a continuous measure. The exposures include all factors listed in addition to the first five genetic ancestry principal components, age, and sex. Results are reported as beta estimate (SE), P‐value. Bolded P‐value indicates P ≤ 0.05. PGS, polygenic score.

¹ Random‐effect inverse variance‐weighted model, whereas others used a fixed effect. For the disease group variable, the reference category is the healthy controls. We also included the following interaction terms to the full model in the Canada sample: GAD‐2 PGS × anxiety (β = −0.01, P = 0.9), GAD‐2 PGS × MS (β = −0.07, P = 0.7), GAD‐2 PGS × sex (β = 0.17, P = 0.4), and in UKB sample: GAD‐2 PGS × anxiety (β = 0.07, P =< 0.001), GAD‐2 PGS × MS (β = 0.14, P = 0.06), GAD‐2 PGS × sex (β = 0.01, P = 0.5).