rs1354034

This is a intron variant variant in the ARHGEF3 gene.

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GWAS Catalog Trait Associations (816)

Genome-wide significant associations (p < 5×10⁻⁸) from the NHGRI-EBI GWAS Catalog.

platelet count

Vuckovic D et al. “The Polygenic and Monogenic Basis of Blood Traits and Diseases.” Cell 182(5):1214-1231.e11 (2020)

Allele C

OR 0.13

p —

N 408,112

Large GWAS

European

Sakaue S et al. “A cross-population atlas of genetic associations for 220 human phenotypes.” Nature Genetics 53(10):1415-1424 (2021)

Allele C

OR 0.11

p —

N 499,097

Large GWAS

multi-ancestry

Kachuri L et al. “Genetic determinants of blood-cell traits influence susceptibility to childhood acute lymphoblastic leukemia.” American Journal of Human Genetics 108(10):1823-1835 (2021)

Allele C

OR —

p 2.0e-320

N 235,256

Large GWAS

European

Astle WJ et al. “The Allelic Landscape of Human Blood Cell Trait Variation and Links to Common Complex Disease.” Cell 167(5):1415-1429.e19 (2016)

Allele C

OR 0.14

p 9.0e-301

N 166,066

Large GWAS

European

Jee YH et al. “Genome-wide association studies in a large Korean cohort identify quantitative trait loci for 36 traits and illuminate their genetic architectures.” Nature Communications 16(1):4935 (2025)

Allele C

OR 0.09

p 7.0e-111

N 153,950

Large GWAS

East Asian

Yang Z et al. “Genetic basis of pregnancy-associated decreased platelet counts and gestational thrombocytopenia.” Blood 143(15):1528-1538 (2024)

Allele C

OR 0.13

p 7.0e-34

N 72,816

Large GWAS

East Asian

Little A et al. “Whole genome sequence analysis of platelet traits in the NHLBI Trans-Omics for Precision Medicine (TOPMed) initiative.” Human Molecular Genetics 31(3):347-361 (2022)

Allele C

OR 7.24

p 6.0e-76

N 61,200

Large GWAS

multi-ancestry

Verma A et al. “Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.” Science (new York, N.y.) 385(6706):eadj1182 (2024)

Allele C

OR 0.08

p 4.0e-29

N 55,712

Major Consortium StudyLarge GWAS

Hispanic or Latin American

Gieger C et al. “New gene functions in megakaryopoiesis and platelet formation.” Nature 480(7376):201-8 (2011)

Allele C

OR 6.85

p 3.0e-54

N 48,666

Large GWAS

European

Jacobs BM et al. “Genetic architecture of routinely acquired blood tests in a British South Asian cohort.” Nature Communications 15(1):8929 (2024)

Allele C

OR 0.10

p 1.0e-53

N 38,000

Large GWAS

South Asian

Hu Y et al. “Multi-ethnic genome-wide association analyses of white blood cell and platelet traits in the Population Architecture using Genomics and Epidemiology (PAGE) study.” Bmc Genomics 22(1):432 (2021)

Allele C

OR 0.06

p 1.0e-10

N 21,347

Large GWAS

Hispanic or Latin American

Burley K et al. “PIK3R3 is a candidate regulator of platelet count in people of Bangladeshi ancestry.” Research and Practice in Thrombosis and Haemostasis 7(4):100175 (2023)

Allele C

OR 0.09

p 3.0e-20

N 20,218

Large GWAS

South Asian

Chen MH et al. “Trans-ethnic and Ancestry-Specific Blood-Cell Genetics in 746,667 Individuals from 5 Global Populations.” Cell 182(5):1198-1213.e14 (2020)

Allele C

OR 0.10

p 9.0e-15

N 15,171

Large GWAS

African American or Afro-Caribbean, African unspecified

Li J et al. “GWAS of blood cell traits identifies novel associated loci and epistatic interactions in Caucasian and African-American children.” Human Molecular Genetics 22(7):1457-64 (2013)

Allele C

OR 9.44

p 4.0e-9

N 14,177

Large GWAS

multi-ancestry

Khader Shameer et al. “A genome- and phenome-wide association study to identify genetic variants influencing platelet count and volume and their pleiotropic effects” Human Genetics (2014)

Allele C

OR 7.97

p 6.0e-24

N 13,582

Large GWAS

European

Schick UM et al. “Genome-wide Association Study of Platelet Count Identifies Ancestry-Specific Loci in Hispanic/Latino Americans.” American Journal of Human Genetics 98(2):229-42 (2016)

Allele C

OR 5.87

p 2.0e-13

N 12,491

Large GWAS

Hispanic or Latin American

Gagnon MF et al. “Interplay between hereditary and acquired factors determines the neutrophil counts in older individuals.” Blood Advances 7(13):3232-3243 (2023)

Allele C

OR 0.17

p 3.0e-9

N 2,465

Large GWAS

European

platelet volume

Vuckovic D et al. “The Polygenic and Monogenic Basis of Blood Traits and Diseases.” Cell 182(5):1214-1231.e11 (2020)

Allele C

OR 0.23

p —

N 408,112

Large GWAS

European

Astle WJ et al. “The Allelic Landscape of Human Blood Cell Trait Variation and Links to Common Complex Disease.” Cell 167(5):1415-1429.e19 (2016)

Allele C

OR 0.23

p —

N 164,454

Large GWAS

European

Yang Z et al. “Genetic basis of pregnancy-associated decreased platelet counts and gestational thrombocytopenia.” Blood 143(15):1528-1538 (2024)

Allele C

OR 0.20

p 2.0e-72

N 71,605

Large GWAS

East Asian

Verma A et al. “Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.” Science (new York, N.y.) 385(6706):eadj1182 (2024)

Allele C

OR 0.13

p 3.0e-56

N 40,412

Major Consortium StudyLarge GWAS

Hispanic or Latin American

Little A et al. “Whole genome sequence analysis of platelet traits in the NHLBI Trans-Omics for Precision Medicine (TOPMed) initiative.” Human Molecular Genetics 31(3):347-361 (2022)

Allele C

OR 0.17

p 2.0e-66

N 23,485

Large GWAS

multi-ancestry

Allele C

OR 0.13

p 9.0e-13

N 21,347

Large GWAS

Hispanic or Latin American

Gieger C et al. “New gene functions in megakaryopoiesis and platelet formation.” Nature 480(7376):201-8 (2011)

Allele C

OR 0.02

p 3.0e-69

N 18,600

Large GWAS

European

Chen MH et al. “Trans-ethnic and Ancestry-Specific Blood-Cell Genetics in 746,667 Individuals from 5 Global Populations.” Cell 182(5):1198-1213.e14 (2020)

Allele C

OR 0.16

p 1.0e-21

N 10,737

Large GWAS

African American or Afro-Caribbean, African unspecified

Khader Shameer et al. “A genome- and phenome-wide association study to identify genetic variants influencing platelet count and volume and their pleiotropic effects” Human Genetics (2014)

Allele C

OR 0.19

p 9.0e-34

N 6,291

Large GWAS

European

Read RW et al. “GWAS and PheWAS of red blood cell components in a Northern Nevadan cohort.” Plos One 14(6):e0218078 (2019)

Allele C

OR 0.15

p 2.0e-13

N 4,675

Large GWAS

multi-ancestry

level of dynein light chain Tctex-type 1 in blood serum

Loya H et al. “A scalable variational inference approach for increased mixed-model association power.” Nature Genetics 57(2):461-468 (2025)

Allele C

OR 0.18

p 7.0e-285

N 47,745

Large GWAS

European

bone morphogenetic protein 6 measurement

Loya H et al. “A scalable variational inference approach for increased mixed-model association power.” Nature Genetics 57(2):461-468 (2025)

Allele C

OR 0.18

p 1.0e-228

N 47,745

Large GWAS

European

y-box-binding protein 2 measurement

Pietzner M et al. “Mapping the proteo-genomic convergence of human diseases.” Science (new York, N.y.) 374(6569):eabj1541 (2021)

Allele T

OR 0.38

p 4.0e-196

N 10,708

Large GWAS

European

calcium-binding and coiled-coil domain-containing protein 2 measurement

Loya H et al. “A scalable variational inference approach for increased mixed-model association power.” Nature Genetics 57(2):461-468 (2025)

Allele C

OR 0.16

p 6.0e-165

N 47,745

Large GWAS

European

Pietzner M et al. “Mapping the proteo-genomic convergence of human diseases.” Science (new York, N.y.) 374(6569):eabj1541 (2021)

Allele C

OR 0.15

p 9.0e-27

N 10,708

Large GWAS

European

level of DNA topoisomerase 2-beta in blood

Loya H et al. “A scalable variational inference approach for increased mixed-model association power.” Nature Genetics 57(2):461-468 (2025)

Allele C

OR 0.16

p 2.0e-161

N 47,745

Large GWAS

European

platelet-to-lymphocyte ratio

Kachuri L et al. “Genetic determinants of blood-cell traits influence susceptibility to childhood acute lymphoblastic leukemia.” American Journal of Human Genetics 108(10):1823-1835 (2021)

Allele T

OR —

p 5.0e-155

N 234,552

Large GWAS

European

proheparin-binding EGF-like growth factor level

Loya H et al. “A scalable variational inference approach for increased mixed-model association power.” Nature Genetics 57(2):461-468 (2025)

Allele C

OR 0.14

p 4.0e-150

N 47,745

Large GWAS

European

level of Delta(14)-sterol reductase LBR in blood

Loya H et al. “A scalable variational inference approach for increased mixed-model association power.” Nature Genetics 57(2):461-468 (2025)

Allele C

OR 0.15

p 4.0e-142

N 47,745

Large GWAS

European

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Research that mentions this SNP (1)

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A genome- and phenome-wide association study to identify genetic variants influencing platelet count and volume and their pleiotropic effects

AssociationN=13,582Khader Shameer et al.(2014)· Human Genetics

A genome-wide association study (GWAS) of platelet count (PLT) and mean platelet volume (MPV) in 13,582 and 6,291 participants respectively from the eMERGE network identified 5 chromosomal regions associated with PLT and 8 with MPV at genome-wide significance (P<5E-8). Key findings include variants in ARHGEF3 (rs1354034, P=6E-24 for PLT; P=9E-34 for MPV), SH2B3 (rs3184504, P=5E-12), and multiple other loci. The study replicated 20 SNPs for PLT and 22 for MPV from prior meta-analyses and demonstrated pleiotropic effects with myocardial infarction, autoimmune, and hematologic disorders through phenome-wide association study (PheWAS).

Traits studied:Autoimmune disordersBlood pressureEosinophil countHematologic disordersMean platelet volume (MPV)Myocardial infarctionPlatelet count (PLT)Type 1 diabetes

PubMed DOI Metascience Observatory

About ARHGEF3

Rho-like GTPases are involved in a variety of cellular processes, and they are activated by binding GTP and inactivated by conversion of GTP to GDP by their intrinsic GTPase activity. Guanine nucleotide exchange factors (GEFs) accelerate the GTPase activity of Rho GTPases by catalyzing their release of bound GDP. This gene encodes a guanine nucleotide exchange factor, which specifically activates two members of the Rho GTPase family: RHOA and RHOB, both of which have a role in bone cell biology. It has been identified that genetic variation in this gene plays a role in the determination of bone mineral density (BMD), indicating the implication of this gene in postmenopausal osteoporosis. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

rs1354034

GWAS Catalog Trait Associations (816)

platelet count

platelet volume

level of dynein light chain Tctex-type 1 in blood serum

bone morphogenetic protein 6 measurement

y-box-binding protein 2 measurement

calcium-binding and coiled-coil domain-containing protein 2 measurement

level of DNA topoisomerase 2-beta in blood

platelet-to-lymphocyte ratio

proheparin-binding EGF-like growth factor level

level of Delta(14)-sterol reductase LBR in blood

Research that mentions this SNP (1)

About ARHGEF3

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