Table 3. Variance of sIL-6R level due to rs2228145, total heritability of sIL-6R level, and estimates from linkage analysis.
Observed variance due to rs2228145 genotype | ||||||||||||
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Genotype | Frequencya | sIL-6R level (10-8 g/mL)b | Genotypic Value | Frequency* sIL-6R | (deviation from μ)2 | Frequency*squared deviation | ||||||
CC | p2= 0.15 | 5.698 | + a | 0.15*5.698 = 0.87 | (5.698- μ)2 = 2.32 | 0.15*2.32 = 0.35 | ||||||
AC | 2pq=0.48 | 4.418 | d | 0.48*4.418 = 2.10 | (4.418- μ)2 = 0.06 | 0.48*0.06 = 0.03 | ||||||
AA | q2= 0.37 | 3.238 | - a | 0.37*3.238 = 1.20 | (3.238- μ)2 = 0.88 | 0.37*0.88 = 0.33 | ||||||
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Total | μ=0.87+2.10+1.20 = 4.17 | VSNP=0.35+0.03+0.33 = 0.71 | ||||||||||
(95% CI: 0.68-0.74) | ||||||||||||
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Extended twin family model estimates | ||||||||||||
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VsIL-6R | VA | VD | VC | VE | V/Vtotal | h2 | d2 | c2 | e2 | |||
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ACDE modelc | Vtotal= 1.35 | 0.89 | 0.08 | 0.00 | 0.38 | 1.00 | 0.66 | 0.06 | 0.00 | 0.28 | ||
ACDE + rs2228145d | Vresidual= 0.66 | 0.24 | 0.02 | 0.01 | 0.39 | Vresidual/Vtotal= 0.49 | 0.18 | 0.01 | 0.01 | 0.29 | ||
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Effect of rs2228145e | VSNP= 0.69 | 0.65 | 0.06 | -0.01 | -0.01 | VSNP/Vtotal= 0.51 | 0.48 | 0.05 | 0.01 | 0.01 | ||
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Linkage analysis estimates | ||||||||||||
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VsIL-6R | VA-linkage | VA-polygenic | VD | VC | VE | V/Vtotal | h2 | d2 | c2 | e2 | ||
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Linkage modeled at rs2228145 | Vtotal=1.39 | 0.96 | 0 | - | - | 0.43 | 1 | 0.69 | - | - | 0.31 | |
Linkage+ association modeled at rs2228145 | Vresidual=0.67 | 0.26 | 0 | - | - | 0.41 | Vresidual/Vtotal =0.48 | 0.19 | - | - | 0.30 |
p=minor allele frequency=0.39 and q=major allele frequency=0.61
Mean sIL-6R level, corrected for age and sex, for each genotype group.
μ= Mean sIL-6R level in the population, estimated from the genotype frequencies and corresponding sIL-6R levels for each genotype group.
ACDE model without SNP effects, in which Vtotal is decomposed into VA, VD, VC, and VE.
Model in which the additive effect of rs2228145 on sIL-6R level is modeled, and the residual variance of sIL-6R (Vresidual=Vtotal - VSNP) is decomposed into VA, VC, VD and VE.
The effect of rs2228145 was inferred from the difference between model c and model d Vtotal=Total (phenotypic) variance of age- and sex-adjusted sIL-6R levels. VSNP= Variance of sIL-6R level attributable to rs2228145, VSNP/Vtotal = Proportion of total (phenotypic) variance sIL-6R level explained by rs2228145, Vresidual/Vtotal= Proportion of total (phenotypic) variance sIL-6R level not explained by rs2228145, VA=Additive genetic variance, VD=Non-additive genetic variance, VC=Sibling-shared environmental variance, VE=Unique environmental variance, h2= VA/Vtotal, d2= VD/Vtotal, c2= VC/Vtotal, e2= VE/Vtotal.
VA-linkage =Variance due to linkage, which is based on the pi-hat measure at rs2228145, derived from the IBD matrix of relatives
VA-polygenic = Variance due to all additive genetic effects that are not captured within the linkage component (i.e. additive genetic variance that is not linked to the IL6R locus), which was estimated from the phenotypic covariance of relatives following the assumption that on average 50% of VA-polygenic is shared among first degree relatives.