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. 2022 Dec 8;13:7592. doi: 10.1038/s41467-022-35354-7

Table 1.

Summary of genome-wide structural variants associated with hematological trait

TOPMed Allele Frequencies Significant single variant association tests
Gene(s) Locus SV Breakpoints¹ SV type² Length (bp) Overall African³ Asian³ Hispanic³ European³ Significant Trait Effect Estimate SE P-value
- 2p11.24 2:88832769-88860930 DEL 28162 1.98E-04 4.06E-05 0 0 2.98E-04 Lymphocytes 1.878 0.310 1.36E-09
WBC 2.813 0.426 3.84E-11
RAB7A 3q21.3 3:128694260-128695207 DUP 948 0.085 0.022 0.031 0.065 0.119 Monocyte prop. −0.002 0.0004 6.91E-09
SRPRB, TF, TOPBP1 3q22.1 3:133621201-133784900 DUP 163700 0.208 0.141 0.308 0.200 0.236 TIBC 20.809 2.209 4.56E-21
UIBC 19.298 2.553 4.09E-14
C3orf36, LINC02000, RAB6B, SLCO2A1, SRPRB, TF 3q22.1-q22.2 3:133786201-134102300 DUP 316100 0.272 0.207 0.358 0.267 0.292 TIBC 17.804 2.324 1.84E-14
UIBC 19.463 2.687 4.35E-13
PSORS1C1 6p21.33 6:31132409-31132465 DEL 57 0.085 0.049 0.075 0.103 0.094 Lymphocytes 0.075 0.012 2.01E-09
- 6p21.32 6:32591559-32591660 DEL 102 0.264 0.167 0.281 0.293 0.293 WBC 0.092 0.015 1.25E-09
- 6p21.1 6:41897089-41897626 DEL 538 0.183 0.079 0.209 0.151 0.235 MCH −0.187 0.022 1.28E-17
MCV −0.595 0.055 3.04E-27
RBC 0.033 0.005 1.57E-12
CCND3 6p21.1 6:41985574-41988887 DEL 3314 0.007 0.002 0.001 0.007 0.010 MCV 1.556 0.256 1.16E-09
- 6p23.3 6:134878573-134878641 DUP 69 0.044 0.072 0.030 0.037 0.036 MCH −0.254 0.046 4.23E-08
- 9q22.1 9:88923551-88924152 DEL 602 0.034 0.117 7.08E-04 0.032 7.31E-04 Monocytes −0.029 0.004 2.20E-11
Monocyte prop. −0.004 −0.004 1.07E-12
ATXN2 12q24.12 12:111538485-111542205 DEL 3721 0.068 0.016 0.021 0.058 0.092 Platelets −6.063 0.820 1.40E-13
ATXN2 12q24.12 12:111542097-111542205 INV 109 0.062 0.015 0.021 0.054 0.085 Platelets −6.371 0.911 2.65E-12
- 14q32.334 14:105863184-105897962 DEL 34779 2.24E-04 4.16E-05 0 0 3.43E-04 Lymphocytes 2.037 0.256 1.87E-15
Lymphocyte prop. 0.228 0.030 2.49E-14
Neutrophil prop. −0.222 0.034 1.08E-10
- 14q32.334 14:105864247-105902650 DEL 38404 7.96E-05 0 0 0 1.41E-04 WBC 3.115 0.483 1.15E-10
HBA1, HBA2 16p13.3 16:165396-184701 DEL 19306 5.95E-05 0 0.004 6.32E-05 0 MCH −6.570 0.865 3.12E-14
MCV −16.599 2.305 5.97E-13
RBC 1.437 0.189 3.02E-14
HBA1, HBA2 16p13.3 16:172001-177200 DEL 5200 0.057 0.176 0.030 0.060 0.008 Hematocrit −0.485 0.054 2.65E-19
Hemoglobin −0.437 0.018 5.06E-127
MCH −2.668 0.038 <5E-324
MCHC −0.701 0.015 <5E-324
MCV −6.276 0.099 <5E-324
RBC 0.296 0.008 <5E-324
RBW 0.545 0.030 1.19E-73
MPV 0.118 0.021 1.60E-08
FAM234A 16p13.3 16:246437-249971 DEL 3535 0.006 0.019 7.39E-04 0.005 7.54E-05 MCH −0.788 0.120 4.90E-11
MCV −1.917 0.310 6.07E-10
CAPN15 16p13.3 16:550075-550141 DEL 67 0.025 0.116 7.05E-04 0.020 3.39E-04 MCH −0.374 0.063 2.92E-09
MCV −0.929 0.162 8.74E-09
KCNJ18 17p11.2 17:21659501-21795800 DUP 136300 0.511 0.519 0.509 0.508 0.508 Lymphocyte prop. 0.022 0.004 4.36E-10
Neutrophils prop. −0.025 0.004 3.90E-10
- 18p11.22 18:9621931-9622237 DEL 307 0.791 0.839 0.921 0.766 0.770 MPV −0.079 0.014 9.32E-09
TMPRSS6 22q12.3 22:37067818-37067888 DUP 71 0.347 0.483 0.323 0.324 0.301 Hemoglobin 0.059 0.010 1.62E-08

¹Structural variant breakpoints predicted by the Parliament2 pipeline.

²Types of structural variant identified: deletions (DEL), duplications (DUP), inversions (INV).

³Discrete ancestry subgroups are based on genetically inferred ancestry and a machine learning algorithm that refines self-identified ancestry.

4Based on location and WGS read visualization SV likely represents a somatic deletion or a complex rearrangement due to V(D)J recombination events.

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.