rs10506328 (NFE2): Platelet Count and Volume Variant
Key takeaways
- Near the NFE2 transcription factor gene, this variant is linked to platelet count and volume variation in large GWAS studies.
- Associations replicated across cohorts with up to 13,582 participants for platelet count and 6,291 for platelet volume.
- Phenome-wide analysis connects this region to myocardial infarction, autoimmune, and hematologic conditions.
- GTEx data shows the ALT allele raises FLJ12825 expression in seven tissue types including skeletal muscle, adipose, and skin.
- All available evidence is from European-ancestry populations only.
Key takeaways
- Near the NFE2 (Nuclear Factor Erythroid 2) transcription factor gene, this variant is linked to platelet count and volume variation in large GWAS studies.
- Associations replicated across cohorts with up to 13,582 participants for platelet count and 6,291 for platelet volume.
- Phenome-wide analysis connects this region to myocardial infarction, autoimmune, and hematologic conditions.
- GTEx data shows the ALT allele raises FLJ12825 expression in seven tissue types including skeletal muscle, adipose, and skin.
- All available evidence is from European-ancestry populations only.
What the research says
A genome-wide association study (GWAS, a method that scans the genome for statistical links between genetic variants and measured traits) and phenome-wide association study (PheWAS, which tests a variant against hundreds of disease diagnoses simultaneously) in the eMERGE network (n=13,582 for platelet count; n=6,291 for mean platelet volume) identified multiple chromosomal regions associated with platelet traits, with associated genes including transcription factors and proteins involved in megakaryocyte (platelet precursor cell) development and platelet production. The HaemGen consortium genome-wide meta-analysis (n=13,943 across six European population-based studies) identified 22 loci associated with eight hematological parameters, 15 of which were linked to platelet parameters. PheWAS analysis revealed pleiotropic (cross-trait) associations between platelet-trait variants and myocardial infarction, autoimmune disorders, and hematologic conditions, using a Bonferroni-corrected significance threshold of P<3.6E-5 across 1,368 diagnoses.
Reported associations
- Platelet count (PLT): Associated with this genomic region in a GWAS of 13,582 European-ancestry eMERGE participants; 5 chromosomal regions reached genome-wide significance (P<5E-8), and 20 of 56 candidate PLT SNPs were replicated.
- Mean platelet volume (MPV): 8 chromosomal regions reached genome-wide significance in the eMERGE GWAS (n=6,291); 22 of 29 candidate MPV SNPs were replicated in meta-analysis.
- Multiple hematological parameters: The HaemGen meta-analysis (n=13,943) confirmed 22 loci across eight blood cell traits, with 15 linked specifically to platelet parameters.
- Myocardial infarction: Pleiotropic PheWAS associations between platelet-trait variants and myocardial infarction were identified at a Bonferroni-corrected threshold (P<3.6E-5 across 1,368 diagnoses).
- Autoimmune and hematologic disorders: Multiple platelet-trait variants showed pleiotropic PheWAS associations with autoimmune and hematologic conditions.
Evidence quality
The evidence base rests on two large-scale European-ancestry studies. The eMERGE GWAS applied a genome-wide significance threshold (P<5E-8) with replication across multiple sites (n up to 13,582 for PLT, 6,291 for MPV). The HaemGen consortium used a two-stage discovery-replication design with 13,943 participants from six independent studies. Both were restricted to European-ancestry populations, which limits generalizability to other groups. Specific effect sizes for rs10506328 individually are not reported in the available study text. Pleiotropic PheWAS findings were Bonferroni-corrected (P<3.6E-5) and should be treated as preliminary signals requiring further investigation. No conflicting findings between the two studies are noted for platelet trait associations.
Tissue-specific expression effects
- FLJ12825: The ALT allele is associated with increased expression in skeletal muscle, subcutaneous adipose tissue, tibial artery, cultured fibroblasts, thyroid, and both sun-exposed and non-sun-exposed skin, with effects reaching significance across all seven tissue types. GTEx Portal
- GPR84: The ALT allele is associated with increased expression in tibial artery tissue. GTEx Portal
Lifestyle considerations No lifestyle considerations on file for this variant.
Frequently asked questions
What is the NFE2 gene and what does it do?
NFE2 (Nuclear Factor Erythroid 2) is a transcription factor gene involved in megakaryocyte development - the process by which platelets are produced from precursor cells in bone marrow. Research into platelet genetics consistently identifies this gene region as relevant to how many platelets circulate and how large they are.
Is rs10506328 linked to platelet disorders?
Large GWAS studies have found this genomic region is associated with variation in platelet count and mean platelet volume. These associations describe population-level variation in platelet traits and do not directly establish a cause of clinical platelet disorders.
Does this variant affect heart disease risk?
Phenome-wide studies found statistical associations between platelet-trait variants in this region and myocardial infarction in large population cohorts. These are population-level associations identified through PheWAS analysis and do not establish individual risk.
What do the GTEx expression results mean for rs10506328?
GTEx data shows the alternative allele is associated with higher expression of the FLJ12825 gene across multiple tissues including skeletal muscle, fat, and skin. This suggests the variant may act as a regulatory element affecting gene activity in tissues well beyond blood cells.
How strong is the evidence for rs10506328?
Platelet trait associations reached genome-wide significance (P<5E-8) and were replicated across multiple cohorts totaling up to 13,582 participants. However, all studies were conducted in European-ancestry populations, and specific effect sizes for this exact variant are not detailed in the available study summaries.