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.