HSD11B1 haplotype blocks and combinations: Two haplotypes

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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.
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