Table 3 Structural variants conditioned on single nucleotide variants/indels from previous genome-wide association studies

From: Whole genome sequencing identifies structural variants contributing to hematologic traits in the NHLBI TOPMed program

 

Marginal

Conditioned on TOPMed¹

Conditioned on BCX²

Gene(s)

Locus

SV Breakpoints

SV type

TOPMed Allele Frequency

Significant Trait

Effect Estimate

Effect Estimate SE

P-value

Effect Estimate

Effect Estimate SE

P-value

Effect Estimate

Effect Estimate SE

P-value

-

2p11.23

2:88832769-88860930

DEL

1.98E-04

Lymphocytes

1.878

0.31

1.36E-09

1.742

0.288

1.49E-09

2.087

0.309

1.42E-11

WBC

2.813

0.426

3.84E-11

2.929

0.42

2.94E-12

3.061

0.419

2.67E-13

RAB7A

3q21.3

3:128694260-128695207

DUP

0.085

Monocyte prop.

−0.002

0.0004

6.91E-09

−0.001

3.93E-04

0.181

−7.31E-04

4.18E-04

0.08

SRPRB, TF, TOPBP1

3q22.1

3:133621201-133784900

DUP

0.208

TIBC

20.809

2.209

4.56E-21

−0.751

2.145

0.726

-

-

-

UIBC

19.298

2.553

4.09E-14

−1.899

3.537

0.591

-

-

-

C3orf36, LINC02000, RAB6B, SLCO2A1, SRPRB, TF

3q22.1-q22.2

3:133786201-134102300

DUP

0.272

TIBC

17.804

2.324

1.84E-14

−1.179

1.972

0.55

-

-

-

UIBC

19.463

2.687

4.35E-13

1.182

3.387

0.727

-

-

-

PSORS1C1

6p21.33

6:31132409-31132465

DEL

0.085

Lymphocytes

0.075

0.012

2.01E-09

0.023

0.029

0.426

0.047

0.014

9.48E-04

-

6p21.32

6:32591559-32591660

DEL

0.264

WBC

0.092

0.015

1.25E-09

0.146

0.061

0.016

0.068

0.016

1.20E-05

-

6p21.1

6:41897089-41897626

DEL

0.183

MCH

−0.187

0.022

1.28E-17

−0.075

0.047

0.108

−0.12

0.046

0.009

MCV

−0.595

0.055

3.04E-27

−0.249

0.119

0.037

−0.267

0.087

0.002

RBC

0.033

0.005

1.57E-12

0.012

0.012

0.313

0.024

0.01

0.018

CCND3

6p21.1

6:41985574-41988887

DEL

7.00E-03

MCV

1.556

0.256

1.16E-09

−0.994

0.845

0.24

−1.597

0.878

0.069

-

6p23.3

6:134878573-134878641

DUP

4.40E-02

MCH

−0.254

0.046

4.23E-08

−0.039

0.052

0.449

−0.093

0.045

0.042

-

9q22.1

9:88923551-88924152

DEL

0.034

Monocytes

−0.029

0.004

2.20E-11

0.014

0.029

0.642

−0.032

0.004

4.64E-13

Monocyte prop.

−0.004

0.001

1.07E-12

0.005

0.004

0.222

−0.005

5.89E-04

2.61E-16

ATXN2

12q24.12

12:111538485-111542205

DEL

0.068

Platelets

−6.063

0.82

1.40E-13

8.886

7.878

0.259

−1.595

1.046

0.127

ATXN2

12q24.12

12:111542097-111542205

INV

0.062

Platelets

−6.371

0.911

2.65E-12

0.385

2.423

0.874

−1.656

1.108

0.135

-

14q32.333

14:105863184-105897962

DEL

2.24E-04

Lymphocytes

2.037

0.256

1.87E-15

2.76

0.258

1.13E-26

2.248

0.254

9.36E-19

Lymphocyte prop.

0.228

0.030

2.49E-14

0.203

0.028

2.31E-13

0.208

0.027

1.71E-14

Neutrophils prop.

−0.222

0.034

1.08E-10

−0.207

0.033

6.33E-10

−0.212

0.033

1.52E-10

-

14q32.333

14:105864247-105902650

DEL

7.96E-05

WBC

3.115

0.483

1.15E-10

3.144

0.471

2.51E-11

3.229

0.472

7.52E-12

HBA1, HBQ1, HBA2

16p13.3

16:165396-184701

DEL

5.95E-05

MCH

−6.57

0.865

3.12E-14

−0.782

2.588

0.762

−6.053

0.808

6.66E-14

MCV

−16.599

2.305

5.97E-13

−2.362

6.497

0.716

−15.189

2.151

1.64E-12

RBC

1.437

0.189

3.02E-14

0.622

0.581

0.284

1.359

0.185

1.99E-13

HBA1, HBA2, HBQ1

16p13.3

16:172001-177200

DEL

0.057

Hematocrit

−0.485

0.054

2.65E-19

−0.467

0.053

1.50E-18

−0.492

0.054

5.05E-20

Hemoglobin

−0.437

0.018

5.06E-127

−0.44

0.025

4.87E-71

−0.449

0.021

8.19E-104

MCH

−2.668

0.038

<5E-324

−2.621

0.06

<5E-324

−2.704

0.041

<5E-324

MCHC

−0.701

0.015

<5E-324

−0.652

0.025

5.87E-156

−0.708

0.016

<5E-324

MCV

−6.276

0.099

<5E-324

−6.22

0.153

<5E-324

−6.483

0.111

<5E-324

RBC

0.296

0.008

<5E-324

0.267

0.012

9.77E-109

0.298

0.009

1.58E-245

RBW

0.545

0.03

1.19E-73

0.509

0.036

1.79E-46

0.566

0.032

3.52E-70

MPV

0.118

0.021

1.60E-08

0.119

0.019

6.23E-10

0.117

0.019

5.99E-10

FAM234A

16p13.3

16:246437-249971

DEL

0.006

MCH

−0.788

0.12

4.90E-11

−0.401

0.264

0.129

−0.86

0.116

1.48E-13

MCV

−1.917

0.31

6.07E-10

−0.502

0.686

0.464

−1.958

0.298

5.41E-11

CAPN15

16p13.3

16:550075-550141

DEL

0.025

MCH

−0.374

0.063

2.92E-09

−0.036

0.072

0.611

−0.412

0.061

1.21E-11

MCV

−0.929

0.162

8.74E-09

−0.27

0.185

0.144

−0.618

0.155

6.86E-05

KCNJ18

17p11.2

17:21659501-21795800

DUP

0.511

Lymphocyte prop.

0.022

0.004

4.36E-10

0.023

0.003

2.17E-11

0.023

0.003

4.07E-11

Neutrophils prop.

−0.025

0.004

3.90E-10

−0.024

0.004

1.56E-09

−0.023

0.004

2.57E-09

-

18p11.22

18:9621931-9622237

DEL

0.791

MPV

−0.079

0.014

9.32E-09

−0.043

0.031

0.167

−0.065

0.03

0.031

TMPRSS6

22q12.3

22:37067818-37067888

DUP

0.347

Hemoglobin

0.059

0.01

1.62E-08

−0.007

0.016

0.669

−0.006

0.015

0.685

  1. ¹Analyses included previously-reported SNVs or small indels with P < 5e-8 in TOPMed single variant association tests (Mikhaylova et al. 2021; Hu et al. 2021).
  2. ²Analysis included TOPMed SNVs and small indels that matched variants reported in Chen et al. 2020 and Vuckovic et al. 2020 as part of the Blood Cell Consortium (BCX).
  3. 3Based on location and WGS read visualization SV likely represents a somatic deletion or a complex rearrangement due to V(D)J recombination events. Conditional analyses were performed for each blood trait. Matched variants on each chromosome were LD-pruned and included as fixed effects in a two-stage LMM association testing. All p-values are derived from two-sided t-tests and are not adjusted for multiple comparisons. WBC White Blood Cells, TIBC Total iron binding capacity, UIBC Unsaturated iron binding capacity, MCH Mean corpuscular hemoglobin, MCV Mean corpuscular volume, RBC Red blood cells, RBW Red cell width, MCHC Mean corpuscular hemoglobin concentration, MPV Mean Platelet Volume.
Back to article page