<p>Brain Structure & Function</p><p>Additive sex-specific influence of common non-synonymous DISC1 variants on amygdala, basal ganglia, and white cortical surface area in healthy young adults</p><p>Christiane Mühle1*, Jakob Kreczi1, Cosima Rhein1, Tanja Richter-Schmidinger1, Panagiotis Alexopoulos1,2, Arnd Doerfler3, Bernd Lenz1§, Johannes Kornhuber1§</p><p>§BL and JK contributed equally.</p><p>*Correspondence Christiane Mühle, Department of Psychiatry and Psychotherapy, Friedrich-Alexander University Erlangen- Nürnberg, Schwabachanlage 6, D-91054 Erlangen, Germany, Tel.: #49-9131-85-44738, Fax: #49-9131-85- 36381, e-mail: [email protected], [email protected]</p><p>Online Resource 1: Demographic and raw volumetric data of the study population for male and female participants (p values for the sex difference of raw or standardized data, p < 0.05 in bold). Values represent the mean ± standard deviation.</p><p> male (n = 51) female (n = 94) p (male-female) p (male-female per ICV) age (years) 25.71 ± 3.36 24.23 ± 3.32 0.005 - intracranial volume (mm³) 1739543 ± 140008 1513508 ± 114566 2 × 10-14 - hippocampus (mm³) 9377 ± 703 8604 ± 729 6 × 10-9 5 × 10-4 caudate (mm³) 8016 ± 955 7364 ± 802 2 × 10-5 0.003 putamen (mm³) 11852 ± 1094 10415 ± 1062 2 × 10-12 0.573 pallidum (mm³) 3709 ± 368 3257 ± 330 4 × 10-12 0.654 nucleus accumbens (mm³) 1201 ± 162 1076 ± 162 2 × 10-5 0.287 amygdala (mm³) 3503 ± 344 3051 ± 260 3 × 10-12 0.977 white cortical surface (mm²) 95890 ± 7494 84572 ± 6539 9 × 10-17 0.120 cortical thickness (mm) 2.61 ± 0.09 2.62 ± 0.09 0.515 -</p><p>Online Resource 2: Standardized brain volumes and surface areas (per ICV) differentiated by sex and genotype for the analyzed SNPs in DISC1.</p><p> male female rs3738401 (p.R264Q) GG (19) AG (26) AA (6) GG (37) AG (44) AA (13) caudate nucleus 4.58 ± 0.46 4.71 ± 0.50 4.33 ± 0.43 4.85 ± 0.50 4.83 ± 0.44 5.11 ± 0.58 putamen 6.62 ± 0.63 7.02 ± 0.57 6.69 ± 0.59 6.77 ± 0.70 6.94 ± 0.63 7.15 ± 0.86 pallidum 2.05 ± 0.20 2.21 ± 0.21 2.15 ± 0.22 2.09 ± 0.18 2.19 ± 0.18 2.23 ± 0.32 nucleus accumbens 0.66 ± 0.07 0.73 ± 0.11 0.68 ± 0.08 0.71 ± 0.11 0.72 ± 0.08 0.71 ± 0.13 amygdala 2.03 ± 0.15 2.06 ± 0.21 1.85 ± 0.17 1.97 ± 0.15 2.05 ± 0.15 2.06 ± 0.25 white cortical surface (1/mm) 55.98 ± 2.19 55.06 ± 2.82 53.33 ± 1.77 55.38 ± 3.04 55.96 ± 1.88 57.47 ± 4.13 rs66752881 (p.L607F) CC (35) CT (14) TT (2) CC (74) CT (18) TT (2) caudate nucleus 4.53 ± 0.47 4.78 ± 0.50 4.95 ± 0.30 4.86 ± 0.47 4.91 ± 0.61 4.97 ± 0.25 putamen 6.80 ± 0.67 6.92 ± 0.49 6.85 ± 0.34 6.83 ± 0.66 7.07 ± 0.72 7.89 ± 1.10 pallidum 2.12 ± 0.21 2.17 ± 0.23 2.26 ± 0.43 2.13 ± 0.17 2.25 ± 0.31 2.27 ± 0.07 nucleus accumbens 0.69 ± 0.10 0.70 ± 0.09 0.70 ± 0.10 0.72 ± 0.10 0.68 ± 0.11 0.77 ± 0.01 amygdala 2.02 ± 0.20 2.03 ± 0.20 2.04 ± 0.16 2.01 ± 0.15 2.07 ± 0.23 2.00 ± 0.22 white cortical surface (1/mm) 55.3 ± 2.75 54.85 ± 2.37 55.76 ± 1.35 55.83 ± 2.55 56.66 ± 3.68 53.6 ± 2.01 rs821616 (p.S704C) AA (26) AT (23) TT (2) AA (50) AT (37) TT (7) caudate nucleus 4.53 ± 0.41 4.74 ± 0.52 4.36 ± 0.83 4.83 ± 0.49 4.91 ± 0.49 5.03 ± 0.50 putamen 6.80 ± 0.54 6.86 ± 0.72 6.96 ± 0.23 6.88 ± 0.63 6.94 ± 0.83 6.83 ± 0.42 pallidum 2.13 ± 0.19 2.14 ± 0.25 2.37 ± 0.19 2.16 ± 0.17 2.16 ± 0.26 2.10 ± 0.17 nucleus accumbens 0.70 ± 0.08 0.69 ± 0.11 0.72 ± 0.18 0.72 ± 0.09 0.71 ± 0.12 0.73 ± 0.05 amygdala 1.95 ± 0.16 2.08 ± 0.19 2.33 ± 0.08 1.99 ± 0.14 2.06 ± 0.20 2.03 ± 0.15 white cortical surface (1/mm) 55.21 ± 2.24 55.29 ± 2.98 53.93 ± 3.02 55.35 ± 2.2 56.58 ± 3.47 56.75 ± 2.01</p><p>1 Online Resource 3: Standardized brain volumes and surface areas (per ICV) differentiated by sex and the combined cumulative genotype score of the three analyzed SNPs (rs3738401, rs6675281 and rs821616) in DISC1 (number of subjects in brackets).</p><p> female combined DISC1 genotype score (n) 4 (22) 5 (13) 6 (9) 7 (2) 3 (16) 4 (32) 5 (30) 6 (13) 7 (3) caudate nucleus 4.60 ± 0.45 4.53 ± 0.55 4.80 ± 0.60 4.84 ± 0.14 4.74 ± 0.54 4.84 ± 0.43 4.91 ± 0.46 4.95 ± 0.57 5.25 ± 0.75 putamen 6.69 ± 0.67 6.88 ± 0.72 7.12 ± 0.36 6.79 ± 0.26 6.68 ± 0.62 6.89 ± 0.75 6.84 ± 0.51 7.14 ± 0.78 7.75 ± 1.30 pallidum 2.05 ± 0.20 2.15 ± 0.22 2.32 ± 0.22 2.17 ± 0.31 2.11 ± 0.17 2.14 ± 0.19 2.14 ± 0.17 2.20 ± 0.22 2.51 ± 0.56 nucleus accumbens 0.67 ± 0.09 0.71 ± 0.12 0.74 ± 0.10 0.65 ± 0.03 0.71 ± 0.10 0.72 ± 0.12 0.71 ± 0.07 0.69 ± 0.10 0.75 ± 0.22 amygdala 2.00 ± 0.14 2.04 ± 0.27 2.11 ± 0.21 1.90 ± 0.05 1.99 ± 0.14 1.99 ± 0.17 2.01 ± 0.13 2.09 ± 0.14 2.30 ± 0.43 white cortical surface (1/mm) 55.18 ± 2.37 55.64 ± 3.46 54.03 ± 2.06 53.83 ± 1.38 54.85 ± 2.95 55.93 ± 2.64 55.68 ± 1.99 56.5 ± 1.96 62.09 ± 6.55</p><p>2</p>