Genetic and environmental influences on circulating NK and T cells and their relation to bipolar disorder

International Journal of Bipolar Disorders

Table 2 Effect of genes and environmental factors on lymphoid subsets in relation of bipolar disorder

Cell population	A. Sources on variance on lymphoid subsets, irrespective of disease (n = 106), % (95% CI)			Phenotypic correlation
Cell population	h²	c²	e²	Rph	p
T helper 17 cells	0.79 (0.35–0.88)	0.009 (NA–0.37)	0.21 (0.11–0.38)	0.02 (− 0.17–0.22)	0.80
T regulator cells	0.69 (0.17–0.85)	0.029 (NA–0.39)	0.28 (0.14–0.55)	0.06 (− 0.13–0.25)	0.53
Total T helper cells	0.59 (0.04–0.87)	0.18 (0.00–0.63)	0.22 (0.12–0.42)	− 0.06 (−0.25–0.13)	0.54
Total T cells	0.57 (0.00–0.82)	0.11 (0.00–0.57)	0.32 (0.18–0.59)	− 0.21 (− 0.38–0.02)	0.03*
T helper 2 cells	0.51 (0.01–0.86)	0.27 (0.00–0.67)	0.22 (0.11–0.47)	0.10 (− 0.09–0.28)	0.30
NK cells	0.50 (0.00–0.82)	0.21 (0.00–0.62)	0.28 (0.14–0.54)	0.18 (0.00–0.34)	0.04*
Monocytes	0.25 (0.09–0.43)	0.30 (0.11–0.51)	0.45 (0.28–0.69)	0.15 (− 0.03–0.32)	0.10
T helper 1 cells	0.19 (0.00–0.74)	0.38 (0.00–0.69)	0.43 (0.24-0.69)	− 0.05 (− 0.23–0.13)	0.57

Cell population	B. Bipolar twins and their co-twins (n = 52)	Healthy control twins (n = 54)
Cell population	M (S.E.)^a	M (S.E)^a	P (MANCOVA/ANCOVA^b)
T helper 17 cells	0.29 (1.07)	0.27 (1.07)	0.349
T regulator cells	1.92 (1.04)	1.83 (1.04)	0.698
Total T helper cells	38.05 (1.18)	38.37 (1.18)	0.402
Total T cells	54.48 (1.18)	59.0 (1.17)	0.015/0.007*
T helper 2 cells	0.68 (1.06)	0.62 (1.6)	0.457
NK cells	12.62 (0.66)	10.01 (0.63)	0.009/0.006*
Monocytes	18.53 (0.81)	16.86 (0.81)	0.181
T helper 1 cells	5.47 (1.07)	5.97 (1.06)	0.553

The different lymphoid subsets and NK cells are displayed in order of highest to lowest source of genetic variance
T helper 17 cells: CD⁴⁺ IL17A. T regulatory cells: CD³⁺ CD25 highFoxP3+. Total T helper cells: CD³⁺ CD⁴⁺ CD⁸⁻;Total T-cells: CD³⁺; T helper 2 cells: CD⁴⁺ IL-4+; NK cells: CD³⁺–CD⁵⁶⁺; Monocytes: CD¹⁴⁺, T helper 1 cells: CD4+ IFN-y+
Monocytes, T cells, T helper cells and NK cells were expressed in the calculations as percentages of intact CD⁴⁵⁺ PBMC
The subsets of T helper cells (T helper 17, T helper 2, T helper 1 and T regulator cells) were expressed in the calculations as percentages of lymphocytes
* Significant at p = 0.05, uncorrected for multiple comparisons
^aTo normalize data some values were transformed, for interpretation the means and standard errors were back transformed
^bp value based on multivariate analysis (MANOVA). A follow-up univariate analysis with post hoc least significance difference (LSD) analysis was performed for NK cells and total T cells