Table 1 Mediating effects of modifiable traits in the associations between PRS of brain disorders and total GMV

From: Modifiable traits and genetic associations with grey matter volume in mid-to-late adulthood: a population-based study in the UK biobank

Disorder

Mediators

Indirect effect [90% CI]

Total effect [90% CI]

Percent

Types

PRS AD

LDL

5.76\(\times\)10−3, [0.004, 0.007] a

6.03\(\times\)10−3, [−0.005, 0.017]

95.66%

Mediation effect

PRS AD

ApoB

5.20\(\times\)10−3, [0.004, 0.007] a

6.02\(\times\)10−3, [−0.005, 0.017]

86.34%

Mediation effect

PRS AD

Cholesterol

4.91\(\times\)10−3, [0.004, 0.006] a

6.03\(\times\)10−3, [−0.005, 0.017]

81.54%

Mediation effect

PRS AD

CRP

3.99\(\times\)10−3, [0.003, 0.005] a

6.02\(\times\)10−3, [−0.005, 0.017]

66.37%

Mediation effect

PRS AD

ApoA1

−0.68\(\times\)10−3, [−0.001, −0.000] a

6.03\(\times\)10−3, [−0.005, 0.017]

−10.08%

Suppression effect

PRS AD

HDL

−0.80\(\times\)10−3 [−0.001, −0.000] a

6.03\(\times\)10−3, [−0.005, 0.017]

−11.73%

Suppression effect

PRS BD

Qualifications

1.25\(\times\)10−3, [0.001, 0.002] a

12.97\(\times\)10−3, [0.003, 0.023] a

9.65%

Mediation effect

PRS BD

Impedance of arm

0.75\(\times\)10−3, [0.000, 0.001] a

12.97\(\times\)10−3, [0.003, 0.023] a

5.77%

Mediation effect

PRS BD

Comparative height size at age 10 (Shorter)

−0.37\(\times\)10−3, [−0.001, −0.000] a

12.97\(\times\)10−3, [0.003, 0.023] a

−2.77%

Suppression effect

PRS BD

Townsend deprivation index

−0.79\(\times\)10−3, [−0.001, −0.000] a

12.97\(\times\)10−3, [0.003, 0.023] a

−5.72%

Suppression effect

PRS BD

Long standing illness

−0.89\(\times\)10−3, [−0.001, −0.000] a

12.97\(\times\)10−3, [0.003, 0.023] a

−6.42%

Suppression effect

PRS BD

Smoking status

−1.23\(\times\)10−3, [−0.002, −0.001] a

12.97\(\times\)10−3, [0.003, 0.023] a

−8.65%

Suppression effect

PRS BD

White blood cell count

−1.24\(\times\)10−3, [−0.002, −0.001] a

12.97\(\times\)10−3, [0.003, 0.023] a

−8.71%

Suppression effect

PRS ISS

Systolic blood pressure

−5.92\(\times\)10−3, [−0.008, −0.004] a

−17.80\(\times\)10−3, [−0.029, −0.006] a

33.24%

Mediation effect

PRS ISS

Diastolic blood pressure

−5.81\(\times\)10−3, [−0.007, −0.004] a

−17.80\(\times\)10−3, [−0.029, −0.006] a

32.62%

Mediation effect

PRS ISS

Body mass index

−4.05\(\times\)10−3, [−0.005, −0.003] a

−17.80\(\times\)10−3, [−0.029, −0.006] a

22.78%

Mediation effect

PRS ISS

Arm fat percentage

−3.04\(\times\)10−3, [−0.004, −0.002] a

−17.80\(\times\)10−3, [−0.029, −0.006] a

17.09%

Mediation effect

PRS ISS

Leg fat percentage

−2.84\(\times\)10−3, [−0.004, −0.002] a

−17.80\(\times\)10−3, [−0.029, −0.006] a

15.96%

Mediation effect

PRS ISS

Whole body fat mass

−2.68\(\times\)10−3, [−0.004, −0.002] a

−17.80\(\times\)10−3, [−0.029, −0.006] a

15.06%

Mediation effect

PRS ISS

High light scatter reticulocyte count

−2.34\(\times\)10−3, [−0.003, −0.002] a

−17.80\(\times\)10−3, [−0.029, −0.007] a

13.16%

Mediation effect

PRS ISS

Urate

−2.27\(\times\)10−3, [−0.003, −0.002] a

−17.80\(\times\)10−3, [−0.029, −0.007] a

12.72%

Mediation effect

PRS ISS

Body fat percentage

−2.25\(\times\)10−3, [−0.003, −0.001] a

−17.80\(\times\)10−3, [−0.029, −0.006] a

12.62%

Mediation effect

PRS ISS

The overall state of health

−2.22\(\times\)10−3, [−0.003, −0.002] a

−17.79\(\times\)10−3, [−0.029, −0.007] a

12.50%

Mediation effect

PRS ISS

Brisk pace

−2.19\(\times\)10−3, [−0.003, −0.001] a

−17.79\(\times\)10−3, [−0.029, −0.007] a

12.34%

Mediation effect

PRS ISS

Neutrophil count

−2.17\(\times\)10−3, [−0.003, −0.001] a

−17.80\(\times\)10−3, [−0.029, −0.007] a

12.22%

Mediation effect

PRS ISS

White blood cell count

−2.01\(\times\)10−3, [−0.003, −0.001] a

−17.80\(\times\)10−3, [−0.029, −0.007] a

11.26%

Mediation effect

PRS ISS

Long standing illness

−1.64\(\times\)10−3, [−0.002, −0.001] a

−17.80\(\times\)10−3, [−0.029, −0.007] a

9.19%

Mediation effect

PRS ISS

Forced vital capacity

−1.61\(\times\)10−3, [−0.002, −0.001] a

−17.79\(\times\)10−3, [−0.029, −0.007] a

9.08%

Mediation effect

PRS ISS

Qualifications

−1.61\(\times\)10−3, [−0.002, −0.001] a

−17.79\(\times\)10−3, [−0.029, −0.007] a

9.04%

Mediation effect

PRS ISS

Forced expiratory volume in 1 second

−1.53\(\times\)10−3, [−0.002, −0.001] a

−17.79\(\times\)10−3, [−0.029, −0.007] a

8.63%

Mediation effect

PRS ISS

CRP

−1.46\(\times\)10−3, [−0.002, −0.001] a

−17.80\(\times\)10−3, [−0.029, −0.007] a

8.19%

Mediation effect

PRS ISS

Reticulocyte count

−1.10\(\times\)10−3, [−0.002, −0.001] a

−17.80\(\times\)10−3, [−0.029, −0.007] a

6.18%

Mediation effect

PRS ISS

HDL

−1.07\(\times\)10−3, [−0.002, −0.001] a

−17.79\(\times\)10−3, [−0.029, −0.007] a

6.03%

Mediation effect

PRS ISS

Weight

−1.07\(\times\)10−3, [−0.002, −0.001] a

−17.80\(\times\)10−3, [−0.029, −0.007] a

6.00%

Mediation effect

PRS ISS

Slow pace

−0.92\(\times\)10−3, [−0.001, −0.000] a

−17.80\(\times\)10−3, [−0.029, −0.007] a

5.15%

Mediation effect

PRS ISS

Frequency of tiredness

−0.91\(\times\)10−3, [−0.001, −0.000] a

−17.80\(\times\)10−3, [−0.029, −0.007] a

5.11%

Mediation effect

PRS ISS

GGT

−0.90\(\times\)10−3, [−0.001, −0.000] a

−17.80\(\times\)10−3, [−0.029, −0.007] a

5.07%

Mediation effect

PRS ISS

Immature reticulocyte fraction

−0.89\(\times\)10−3, [−0.001, −0.000] a

−17.80\(\times\)10−3, [−0.029, −0.007] a

5.02%

Mediation effect

PRS ISS

Maternal smoking around birth

−0.65\(\times\)10−3, [−0.001, −0.000] a

−17.80\(\times\)10−3, [−0.029, −0.007] a

3.66%

Mediation effect

PRS ISS

Cystatin C

−0.60\(\times\)10−3, [−0.001, −0.000] a

−17.80\(\times\)10–3, [−0.029, −0.007] a

3.37%

Mediation effect

PRS MDD

The overall state of health

−1.05\(\times\)10–3, [−0.002, −0.000] a

−10.19\(\times\)10−3, [−0.022, 0.002]

10.34%

Mediation effect

PRS PD

Qualifications

0.77\(\times\)10−3, [0.000, 0.001] a

10.87\(\times\)10−3, [0.000, 0.021] a

7.12%

Mediation effect

PRS SCZ

Smoking status

−1.41\(\times\)10−3, [−0.002, −0.001] a

−3.45\(\times\)10−3, [−0.014, 0.007]

40.92%

Mediation effect

PRS SCZ

White blood cell count

−1.39\(\times\)10−3, [−0.002, −0.001] a

−3.45\(\times\)10−3, [−0.014, 0.007]

40.43%

Mediation effect

PRS SCZ

Townsend deprivation index

−1.14\(\times\)10−3, [−0.002, −0.001] a

−3.45\(\times\)10−3, [−0.014, 0.007]

33.08%

Mediation effect

PRS SCZ

The overall state of health

−1.01\(\times\)10−3, [−0.002, −0.001] a

−3.45\(\times\)10−3, [−0.014, 0.007]

29.24%

Mediation effect

PRS SCZ

Tea intake

−0.71\(\times\)10−3, [−0.001, −0.000] a

−3.45\(\times\)10−3, [−0.014, 0.007]

20.74%

Mediation effect

PRS SCZ

Getting up in morning

−0.68\(\times\)10−3, [−0.001, −0.000] a

−3.45\(\times\)10−3, [−0.014, 0.007]

19.75%

Mediation effect

PRS SCZ

Frequency of tiredness

−0.67\(\times\)10−3, [−0.001, −0.000] a

−3.45\(\times\)10−3, [−0.014, 0.007]

19.44%

Mediation effect

PRS SCZ

Lymphocyte count

−0.62\(\times\)10−3, [−0.001, −0.000] a

−3.45\(\times\)10−3, [−0.014, 0.007]

18.05%

Mediation effect

PRS SCZ

Alcohol intake frequency

−0.38\(\times\)10−3, [−0.001, −0.000] a

−3.45\(\times\)10−3, [−0.014, 0.007]

10.96%

Mediation effect

PRS SCZ

Impedance of arm

0.98\(\times\)10−3, [0.001, 0.002] a

−3.44\(\times\)10−3, [−0.014, 0.007]

−22.11%

Suppression effect

PRS SCZ

Impedance of leg

1.14\(\times\)10−3, [0.001, 0.002] a

−3.44\(\times\)10−3, [−0.014, 0.007]

−24.86%

Suppression effect

  1. All coefficients reported are derived from mediation models after adjusting for common covariates affecting both GMV and the modifiable traits. Only significant mediating effects are shown following Bonferroni correction. The negative percentage indicates the presence of a suppression effect, where the mediator variable masks the true relationship between the independent and dependent variables. Detailed results, including additional analyses and supporting data, are provided in Supplementary Fig. 5.
  2. a Significant effects were observed in the mediation models that survived Bonferroni correction. LDL low density lipoprotein, ApoB apolipoprotein B, CRP C-reactive protein, ApoA1 apolipoprotein A1, HDL high-density lipoprotein, GGT Gamma-glutamyl transferase.
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