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. 2021 Jul 23;11:406. doi: 10.1038/s41398-021-01518-0

Table 1.

Details of the 30 most significant associations between APOE-ε4, APOE-ε2, polygenic risk (AD PRS) and AD familial risk and traits in the UK Biobank.

Phenotype Category APOE-ε4 APOE-ε2 Familial risk Polygenic score
Est (SE) P r2 Est (SE) P r2 Est (SE) P r2 Est (SE) P r2
Apolipoprotein B Blood biochemistry 0.24 (0.0039) <1 × 10−308 0.025 −0.69 (0.0055) <1 × 10−308 0.09 0.007 (0.0064) 0.28 9.5 × 10−4 −0.2 (0.82) 0.8 2.9 × 10−7
C reactive protein Blood biochemistry −0.26 (0.0041) <1 × 10−308 0.02 0.039 (0.0057) 1.1 × 10−11 0.0023 5.2 × 10−4 (0.0068) 0.94 −9.8 × 10−5 1.2 (0.83) 0.14 3.3 × 10−5
Cholesterol Blood biochemistry 0.17 (0.0039) <1 × 10−308 0.013 −0.42 (0.0055) <1 × 10−308 0.036 0.0075 (0.0065) 0.25 5.3 × 10−4 0.048 (0.8) 0.95 1.1 × 10−5
LDL direct Blood biochemistry 0.19 (0.0039) <1 × 10−308 0.015 −0.54 (0.0055) <1 × 10−308 0.058 0.0046 (0.0065) 0.48 9.1 × 10−4 −0.089 (0.82) 0.91 5.4 × 10−8
Apolipoprotein A Blood biochemistry −0.092 (0.0039) 5.4 × 10−121 0.0021 0.099 (0.0055) 4.6 × 10−73 5.8 × 10−4 −3.2 × 10−4 (0.0065) 0.96 −8.4 × 10−4 0.57 (0.79) 0.47 2.6 × 10−6
Triglycerides Blood biochemistry 0.073 (0.004) 2.4 × 10−75 −0.001 0.12 (0.0056) 2.4 × 10−99 0.0022 0.0039 (0.0066) 0.55 7.1 × 10−4 0.62 (0.8) 0.44 2.8 × 10−6
HDL cholesterol Blood biochemistry −0.064 (0.0038) 5.5 × 10−63 9.4 × 10−4 0.054 (0.0053) 6.1 × 10−24 −0.0012 0.0027 (0.0063) 0.66 −0.001 0.51 (0.77) 0.51 2.0 × 10−6
RDW Blood cell traits −0.05 (0.0045) 8.5 × 10−29 5.8 × 10−4 0.1 (0.0063) 1.0 × 10−57 0.0023 −0.0011 (0.0074) 0.88 −3.8 × 10−5 −0.48 (0.88) 0.59 1.4 × 10−6
Illness, injury...* Psychosocial health −0.015 (0.0086) 0.093 −0.0011 0.005 (0.012) 0.68 9.0 × 10−5 0.22 (0.014) 1.4 × 10−55 0.0012 −0.51 (1.7) 0.77 2.5 × 10−7
Lipoprotein A Blood biochemistry −0.024 (0.0048) 6.9 × 10−7 4.1 × 10−4 −0.11 (0.0068) 2.5 × 10−54 0.001 −0.0081 (0.008) 0.31 −3.1 × 10−4 −1.9 (0.98) 0.053 2.1 × 10−5
Direct bilirubin Blood biochemistry −0.029 (0.0044) 2.0 × 10−11 0.0018 0.081 (0.006) 1.1 × 10−40 0.0015 −0.017 (0.0072) 0.022 5.3 × 10−4 0.11 (0.87) 0.9 5.9 × 10−7
Immature retic. fraction Blood cell traits −0.023 (0.0046) 5.6 × 10−7 5.1 × 10−5 −0.076 (0.0064) 1.7 × 10−32 9.9 × 10−4 0.0048 (0.0076) 0.52 3.7 × 10−5 3 (0.9) 8.1 × 10−4 1.5 × 10−4
HL retic. percentage Blood cell traits −0.0066 (0.0046) 0.15 −3.2 × 10−6 −0.071 (0.0064) 1.1 × 10−28 8.5 × 10−4 0.0023 (0.0075) 0.76 2.2 × 10−5 4.1 (0.9) 6.6 × 10−6 1.0 × 10−4
HL retic. count Blood cell traits −0.0072 (0.0046) 0.12 8.5 × 10−5 −0.069 (0.0064) 9.1 × 10−27 7.9 × 10−4 0.0018 (0.0076) 0.81 4.8 × 10−5 4.1 (0.9) 5.7 × 10−6 1.0 × 10−4
Alanine aminotransferase Blood biochemistry −0.04 (0.0039) 4.3 × 10−24 −7.8 × 10−4 0.018 (0.0055) 0.0014 −4.4 × 10−4 0.0066 (0.0065) 0.31 0.0011 0.79 (0.79) 0.32 1.1 × 10−6
Neuroticism score Psychosocial health 0.0042 (0.014) 0.77 2.3 × 10−4 0.045 (0.02) 0.028 4.7 × 10−4 0.23 (0.024) 9.3 × 10−22 5.3 × 10−4 0.078 (2.9) 0.98 3.8 × 10−9
Freq. of tiredness...* Psychosocial health −0.0067 (0.0033) 0.041 4.9 × 10−4 0.011 (0.0046) 0.016 6.0 × 10−4 0.051 (0.0054) 1.6 × 10−21 −5.4 × 10−06 0.35 (0.65) 0.59 1.3 × 10−6
Glycated haemoglobin Blood biochemistry −0.037 (0.0041) 4.7 × 10−20 −5.1 × 10−4 0.011 (0.0057) 0.059 0.0023 −0.0093 (0.0067) 0.17 3.5 × 10−4 −0.76 (0.81) 0.35 4.2 × 10−6
Seen GP for nerves...* Psychosocial health 0.004 (0.0092) 0.66 5.5 × 10−4 0.0042 (0.013) 0.74 −2.0 × 10−4 0.14 (0.015) 7.5 × 10−20 5.0 × 10−4 0.57 (1.8) 0.76 3.4 × 10−7
Freq. of depressed...* Psychosocial health 0.0027 (0.0024) 0.27 −4.0 × 10−5 0.0022 (0.0034) 0.52 4.3 × 10−4 0.036 (0.004) 2.5 × 10−19 1.8 × 10−5 0.19 (0.48) 0.7 1.5 × 10−5
Non-cancer illnesses...* General health −0.0017 (0.0032) 0.6 0.0059 0.011 (0.0044) 0.013 −0.0053 0.046 (0.0052) 9.4 × 10−19 −0.0027 0.074 (0.64) 0.91 1.4 × 10−6
Retic. percentage Blood cell traits 0.0039 (0.0046) 0.4 1.2 × 10−4 −0.055 (0.0064) 2.3 × 10−17 5.0 × 10−4 5.0 × 10−4 (0.0076) 0.95 2.3 × 10−5 3.8 (0.9) 2.6 × 10−5 1.4 × 10−4
Creatinine Blood biochemistry −0.026 (0.0034) 9.9 × 10−15 0.0013 0.024 (0.0047) 2.5 × 10−7 6.2 × 10−4 −0.0084 (0.0056) 0.13 4.9 × 10−4 1.2 (0.68) 0.085 1.4 × 10−5
Retic. count Blood cell traits 0.0037 (0.0046) 0.42 2.2 × 10−4 −0.05 (0.0064) 1.0 × 10−14 4.3 × 10−4 3.0 × 10−4 (0.0076) 0.97 4.8 × 10−5 3.7 (0.9) 3.9 × 10−5 1.4 × 10−4
Alkaline phosphatase Blood biochemistry −0.031 (0.0041) 1.7 × 10−14 2.0×10−4 0.025 (0.0057) 1.0 × 10−5 8.5 × 10−4 −0.0061 (0.0067) 0.36 8.7 × 10−4 2.2 (0.82) 0.0061 1.3 × 10−5
Diabetes* Metabolic health −0.18 (0.024) 4.5 × 10−14 0.0016 0.21 (0.032) 1.6 × 10−10 0.0074 −0.062 (0.039) 0.11 0.0018 −14 (4.7) 0.0038 1.6 × 10−4
Substitution Test* Cognitive function −0.053 (0.0071) 9.5 × 10−14 −2.7 × 10−4 −0.0066 (0.0098) 0.5 −0.0058 −0.03 (0.011) 0.0065 −0.0011 −1.1 (1.2) 0.32 1.6 × 10−5
SHBG Blood biochemistry 0.028 (0.0038) 1.1 × 10−13 0.0019 0.0085 (0.0054) 0.11 −0.0056 −0.011 (0.0063) 0.082 0.0014 −0.5 (0.77) 0.51 2.2 × 10−6
Insomnia General health −0.0094 (0.003) 0.0016 1.0 × 10−4 0.009 (0.0042) 0.03 7.5 × 10−4 0.035 (0.0049) 5.2 × 10−13 2.9 × 10−4 −0.066 (0.6) 0.91 1.3 × 10−7
Urea Blood biochemistry −0.029 (0.004) 1.0 × 10−12 9.6 × 10−5 0.011 (0.0056) 0.043 7.9 × 10−4 −0.0055 (0.0066) 0.4 1.6 × 10−4 1.4 (0.81) 0.078 1.2 × 10−6

These analyses correspond to the 30 most significant associations from Fig. 1, in which association analyses between the genetic risk factors and UK Biobank traits (described in the “Methods” section) were controlled for age, age2, sex, age*sex interaction term, socioeconomic status based on Townsend deprivation index, genotyping batch, assessment centre, and the first 12 principal components of ancestry, self-reported CVD, statin use, parental CVD and lifestyle score in the models. P-values shown in bold a significant (P < 4.5 × 10−5; see Methods). See Supplementary Table 1 for full association results corresponding to all 273 traits.

RDW Red blood cell erythrocyte distribution width; Illness injury…* Illness, injury, bereavement, stress in last 2 years; retic. reticulocyte; HL High light scatter; Freq. of tiredness…* Frequency of tiredness/lethargy in last 2 weeks; Seen GP for nerves…* Seen doctor (GP) for nerves, anxiety, tension or depression; Freq. of depressed…* Frequency of depressed mood in last 2 weeks; Non-cancer illnesses* Number of self-reported non-cancer illnesses; Diabetes* Diabetes diagnosed by doctor; Substitution Test* Symbol Digit Substitution Test.