Table 2 Association results of the fasting insulin (FI) polygenic scores (PSs) with neurological outcomes in the pooled sample of studies included in the testing set

From: Association of genetic scores related to insulin resistance with neurological outcomes in ancestrally diverse cohorts from the Trans-Omics for Precision Medicine (TOPMed) program

 

Effect estimates in the pooled sample

 

B

SE

P

Dementia (N = 9388; N cases = 1124)

 Cross-population PSFI

0.039

0.039

0.320

 European PSFI

0.046

0.048

0.341

 African American PSFI

0.021

0.064

0.739

Alzheimer’s disease (N = 9388; N cases = 880)

 Cross-population PSFI

0.039

0.044

0.370

 European PSFI

0.046

0.054

0.398

 African American PSFI

0.025

0.071

0.728

General Cognitive Function (N = 19,191)

 Cross-population PSFI

−0.009

0.007

0.174

 European PSFI

−0.008

0.008

0.339

 African American PSFI

−0.010

0.01

0.367

 Hispanic PSFI

−0.004

0.007

0.591

Hippocampal Volume (N = 7674)

 Cross-population PSFI

0.004

0.009

0.653

 European PSFI

−0.004

0.011

0.682

 African American PSFI

0.009

0.015

0.559

 Hispanic PSFI

0.008

0.009

0.398

Total Brain Volume (N = 7674)

 Cross-population PSFI

−0.395

0.457

0.387

 European PSFI

−0.613

0.563

0.276

 African American PSFI

−0.950

0.769

0.217

 Hispanic PSFI

0.317

0.485

0.512

Lateral Ventricular Volume (N = 7674)

 Cross-population PSFI

0.010

0.005

0.041

 European PSFI

0.016

0.006

0.015

 African American PSFI

0.004

0.008

0.667

 Hispanic PSFI

0.002

0.005

0.674

Total Cranial Volume (N = 7674)

 Cross-population PSFI

−6.135

1.405

1.3 × 10−5

 Cross-population PSFI model adjusted for height

−6.545

1.385

2.3 × 10−6

 European PSFI

−9.847

1.776

3.0 × 10−8

 European PSFI model adjusted for height

−10.088

1.750

8.2 × 10−9

 European PSFI model adjusted for height & BMI

−10.638

1.968

6.5 × 10−8

 European PSFI model adjusted for height, excluding participants with prevalent diabetes at the time of neurological traits measurement

−10.775

1.863

7.3 × 10−9

 European PSFI model adjusted for height in APOE-ε4 non-carriers

−10.685

2.154

7.1 × 10−7

 African American PSFI

−2.327

2.338

0.320

 Hispanic PSFI

−0.702

1.446

0.627

  1. AD/Dementia: N = 9382 (89% EA, 11% AA); Cross-Population PSFI (weighted linear combination from regression of population-specific scores on HOMA-IR in the validation set): 0.16 × PSFI_EA + 0.05 × PSFI_AA, where EA means Non-Hispanic White and AA Black/African American.
  2. General Cognitive Function: N = 17,707 (69% EA, 25% AA, 6% HA); Cross-Population PSFI (weighted linear combination from regression of population-specific scores on HOMA-IR in the validation set): 0.12 × PSFI_EA + 0.11 × PSFI_AA + 0.03 × PSFI_HA, where EA means Non-Hispanic White, AA Black/African American, and HA Hispanic Latino American.
  3. Brain MRI Volumes and Total Cranial Volume: N = 7567 (61% EA, 21% AA, 16% HA); Cross-Population PSFI (weighted linear combination from regression of population-specific scores on HOMA-IR in the validation set): 0.11 × PSFI_EA + 0.09 × PSFI_AA + 0.08 × PSFI_HA, where EA means Non-Hispanic White, AA Black/African American, and HA Hispanic Latino American.
  4. Threshold for significance: P = 0.05/4/7 = 0.0018.
  5. P-values in bold and italics are significant after multiple-testing correction.
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