HSD11B1 haplotype blocks and combinations: Two haplotypes blocks were observed from the seven studied HSD11B1 SNPs: rs846910-rs3753519 and rs12565406-rs10863782 (supplementary Figure 1). Regarding the former hapoltype block, by combining the 2 SNPs rs846910G>A and rs3753519G>A: 3 groups were formed, patients with wild-type genotype for both SNPs (rs846910GG/rs3753519GG), wild-type for rs846910 and carriers of the variant allele of rs3753519 (rs846910GG/rs3753519GA-AA) and carriers of the variant allele of both SNPs (rs846910GA-AA/rs3753519GA-AA). None of the patients were carriers of the variant allele of rs846910 and wild-type for rs3753519 (rs846910GA-AA /rs3753519GG). A small increase of the effect was observed in patients carrying the variant alleles of the 2 SNPs compared to the other genotypes and also as compared to the carriers of the variant allele of each SNP separately (Supplementary Table 9). This effect was mainly observed in the female subgroup, in which carriers of the variant allele of both SNPs (rs846910 and rs3753519) showing 4.2 kg/m2, 9.0 cm and 5.1 mmHg lower BMI, WC and diastolic blood pressure (DBP), respectively, as compared to patients with wild-type genotype explaining 5.05, 5.09 and 2.02% of BMI, WC and DBP variance, respectively. Haplotypes formed from the second block, rs12565406-rs10863782, did not show any significant association with the investigated components of the MetS and BMI (data not shown). Supplementary Table 9: Associations between the combination of HSD11B1 rs846910G>A and rs3753519G>A SNPs and BMI and MetS components during follow-up in the main psychiatric study sample and the 3 combined samples: n BMI GG/GG GG/GA-AA GA-AA/GA-AA Men E. Var. 450 n β (95% C.I.) Women p-value 193 ref -2.02 (-3.17 - (-)1.17) -2.50 (-3.59 - (-)1.38) Waist circumference GG/GG GG/GA-AA GA-AA/GA-AA <0.0001§ <0.0001§ 2.94 Diastolic pressure GG/GG GG/GA-AA GA-AA/GA-AA 386 Fasting glucose GG/GG GG/GA-AA GA-AA/GA-AA 294 Triglycerides GG/GG GG/GA-AA GA-AA/GA-AA 312 0.11 0.22 0.17 0.49 167 ref -2.37 (-4.10 - 0.80) -3.28 (-5.90 - 0.74) 0.39 0.46 123 ref -0.17 (-0.47 - (-)0.01) 0.03 (-0.30 - 0.21) 0.22 0.33 128 ref -0.05 (-0.28 – 0.22) 0.00 (-0.22 - 0.20) 0.57 0.38 126 NA 0.002 <0.0001§ 5.05 ref -7.04 (-11.81 - (-)1.69) -9.04 (-12.41 - (-)5.31) 0.007 <0.0001§ 5.09 ref 0.22 (-3.55 - 3.78) -2.99 (-6.60 - 2.18) 0.35 0.12 ref -3.45 (-5.45 - 0.08) -5.05 (-9.06 - (-)1.71) 0.028 0.002 ref -0.15 (-0.36 - 0.01) -0.11 (-0.40 - 0.10) 0.06 0.19 ref -0.07 (-0.44 - 0.35) 0.04 (-0.34 - 0.20) 0.39 0.34 ref 0.02 (-0.13 - 0.17) 0.06 (-0.03 - 0.21) 0.42 0.15 184 ref -0.03 (-0.56 - 0.52) 0.06 (-0.19 - 0.29) 0.45 0.46 ref -2.33 (-3.69 - (-)0.83) -4.21 (-6.04 - (-)2.97) 171 ref -0.22 (-0.83 - 0.22) 0.11 (-0.64 - 0.69) 0.02 0.42 E. Var 219 ref -1.20 (-4.99 - 3.31) -1.01 (-3.96 - 2.79) 0.07 0.05 p-value 219 ref -3.12 (-9.13 - 2.59) -0.49 (-3.99 - 3.76) 0.33 0.29 β (95% C.I.) 255 ref -3.34 (-6.15 - 2.44) -2.72 (-6.99 - 2.95) 167 ref -0.86 (-3.31 - 2.29) -1.72 (-4.40 - 2.37) n 0.007 0.31 204 386 E. Var. 257 ref -1.68 (-2.73 - (-)0.65) -0.43 (-1.88 - 1.00) NA Systolic pressure GG/GG GG/GA-AA GA-AA/GA-AA HDL-cholesterol GG/GG GG/GA-AA GA-AA/GA-AA main psychiatric sample p-value β (95% C.I.) 185 ref -0.01 (-0.14 - 0.10) -0.03 (-0.17 - 0.10) 0.40 0.41 2.02 Combined psychiatric sample Men Women BMI 802 396 406 GG/GG ref ref ref GG/GA-AA -2.16 (-2.92 - (-)1.45) <0.0001§ -1.93 (-2.97 - (-)1.26) <0.0001§ -2.39 (-3.27 - (-)1.32) 0.0001 GA-AA/GA-AA -1.65 (-2.34 - (-)0.65) 0.0002 1.97 -0.46 (-1.41 - 0.43) 0.25 -2.69 (-3.79 - (-)1.58) <0.0001§ 2.96 Genotype combinations: GG/GG: wild-type genotype for both SNPs (rs846910 and rs3753519), GG/GA-AA: wild-type for rs846910 and carriers of the variant allele of rs3753519, GA-AA/GAAA: carriers of the variant allele of both SNPs (rs846910 and rs3753519) Results were obtained by fitting Generalized Additive Mixed Models for patients, controlling for age, sex (whenever appropriate), smoking status, current psychotropic drug and comedications possibly causing weight-gain for BMI and waist circumference analyses, antihypertensive intake for blood pressure analyses, antidiabetic agent for fasting glucose analyses and hypolipidemic agents for triglycerides and HDL-cholesterol analyses. § 10000 bootstraps were used for this analysis. 1000 bootstraps were done for the rest of the rest of the analyses. E. Var.: explained variance by the polymorphism (%), only calculated for significant tests ref: reference, NA: non-applicable.