Hematological
Introduction
Section titled “Introduction”Hematological measurements refer to the quantitative and qualitative assessment of blood components, including red blood cells, white blood cells, and platelets, as well as various proteins and other substances found in blood plasma. These measurements provide a snapshot of an individual’s circulatory health and overall physiological state. Common hematological phenotypes include red blood cell count (RBCC) and hematocrit, which measures the proportion of blood volume occupied by red blood cells.[1]
Biological Basis
Section titled “Biological Basis”The production and regulation of blood cells are complex biological processes primarily occurring in the bone marrow. These processes, known as hematopoiesis, are tightly controlled by a network of growth factors, cytokines, and genetic pathways. Genetic variations can influence these pathways, leading to differences in hematological traits among individuals. For instance, genes such as_HBB_, _HBD_, _HBG1_, _HBG2_, and _HBE1_, which are involved in hemoglobin synthesis, have been associated with variations in hematological phenotypes like hematocrit.[1]Single nucleotide polymorphisms (SNPs) within or near these genes, such as*rs10488676 * and *rs10499199 *, have been identified as contributing to these variations.[1]
Clinical Relevance
Section titled “Clinical Relevance”Hematological measurements are fundamental tools in clinical medicine for the diagnosis, monitoring, and prognosis of a wide range of conditions. Deviations from normal ranges can indicate underlying health issues, such as anemia (low red blood cell count or hemoglobin), polycythemia (high red blood cell count), infections (abnormal white blood cell counts), or bleeding disorders (platelet abnormalities). Regular blood tests, including complete blood counts (CBCs), are routine components of preventive healthcare and disease management, allowing clinicians to detect early signs of disease and tailor treatment strategies.
Social Importance
Section titled “Social Importance”The widespread use and diagnostic power of hematological measurements make them critical for public health. They contribute to large-scale health screenings, inform public health policies, and are essential for blood donation and transfusion services. Understanding the genetic determinants of hematological traits, particularly through studies like genome-wide association analyses, can lead to more personalized medicine approaches, improved diagnostic accuracy, and the development of novel therapeutic interventions for blood disorders, ultimately enhancing quality of life and reducing disease burden across populations.
Methodological and Statistical Constraints
Section titled “Methodological and Statistical Constraints”Research into hematological parameters is subject to several methodological and statistical limitations that can influence the interpretation and generalizability of findings. Many studies, particularly early genome-wide association studies (GWAS), were often limited by relatively small sample sizes, which can result in insufficient statistical power to detect genetic variants with small effect sizes, potentially missing genuine associations.[1], [2] Furthermore, issues such as genomic inflation factors, where observed test statistics are higher than expected by chance, indicate potential biases or unaccounted population structures, complicating the accurate estimation of genetic effects.[3] While stringent quality control measures for SNPs and imputation quality are applied to enhance data reliability, these filters can also influence the range of detectable genetic variation.[2], [4]The complex nature of hematological traits also poses challenges for statistical modeling and replication. The choice of statistical methods, such as linear regression versus linear mixed-effects models, and the adjustment for covariates like age, sex, and population stratification, are critical for valid association testing.[4] Moreover, the extensive multiple testing inherent in genome-wide analyses necessitates very conservative significance thresholds, which can lead to the omission of true but modest genetic signals. This is further compounded by the observation that some initial associations may not maintain significance after more comprehensive multivariable adjustments or in independent replication cohorts, highlighting the need for robust study designs and validation efforts.[1]
Generalizability and Phenotypic Nuances
Section titled “Generalizability and Phenotypic Nuances”A significant limitation in understanding the genetics of hematological traits is the restricted generalizability of findings across diverse populations. Many studies have historically focused on cohorts of specific ancestries, such as Caucasians or African Americans, meaning results may not be directly applicable to other racial or ethnic groups due to differences in genetic architecture and allele frequencies.[1], [4]This lack of ancestral diversity limits the comprehensive understanding of genetic contributions to hematological variation globally and can hinder the development of broadly applicable diagnostic or therapeutic strategies. Addressing this requires more inclusive research involving diverse populations to uncover population-specific and shared genetic determinants.
Beyond ancestry, the precise definition and of hematological phenotypes can introduce variability and heterogeneity across studies. While quality control measures are implemented for laboratory tests and DNA samples to ensure data integrity, subtle differences in phenotyping protocols, laboratory equipment, or sample handling can affect the consistency and comparability of results.[2] These phenotypic nuances, coupled with potential issues in genetic data quality like imputation accuracy, can impact the robustness of identified genetic associations. Such variations necessitate careful consideration when synthesizing findings from multiple studies and underscore the importance of standardized phenotyping protocols for improved comparability and meta-analysis.
Unexplained Variation and Environmental Influences
Section titled “Unexplained Variation and Environmental Influences”Despite advances in identifying genetic associations for hematological traits, a substantial portion of their heritability often remains unexplained, a phenomenon known as “missing heritability.” This gap suggests that current genetic studies may not fully capture all contributing factors, including rare genetic variants, structural variations, or complex epigenetic modifications that were not comprehensively assessed in the provided studies. Furthermore, environmental factors and gene-environment interactions are powerful, yet often unmeasured, confounders that can significantly influence hematological parameters. Lifestyle, diet, infections, and other external exposures can modify the expression of genetic predispositions, and without their comprehensive assessment, the full picture of genetic influence remains incomplete.
The presence of unexplained genomic inflation in some analyses and the inability to identify highly plausible candidate genes near certain statistically significant but not genome-wide significant SNPs indicate persistent knowledge gaps.[1], [3]These limitations underscore that the current understanding of the genetic and environmental interplay governing hematological traits is still evolving. Future research needs to integrate more comprehensive environmental data, explore epigenetic mechanisms, and investigate gene-environment interactions to fully elucidate the complex etiology of these essential physiological parameters. This holistic approach is crucial for translating genetic discoveries into clinical applications and improving personalized medicine for hematological conditions.
Variants
Section titled “Variants”The genetic landscape influencing hematological traits is complex, with numerous single nucleotide polymorphisms (SNPs) and genes playing roles in cell development, function, and immune regulation. Among these, variants in genes likeNLRP12, MYADM-AS1, and regulatory elements such as MIR373 are notable for their potential impact on blood cell parameters. NLRP12 (NLR family pyrin domain containing 12) is a key component of the innate immune system, sensing pathogens and danger signals to modulate inflammatory responses. Variations such as rs62143194 , rs62143199 , and rs3974831 within NLRP12 could alter its function, thereby influencing systemic inflammation, which is known to affect the production and maturation of various blood cell types, including red blood cells, white blood cells, and platelets.[1] Similarly, variants like rs7257867 , rs4806509 , and rs12972849 located near the NLRP12 and MYADM-AS1 (Myeloid Associated Differentiation Marker Antisense RNA 1) genes may affect myeloid cell differentiation and immune cell counts. Additionally, microRNA MIR373 and its associated variants rs8103186 , rs149287489 , and rs3859507 are involved in post-transcriptional gene regulation, providing another layer of control over immune responses and, consequently, hematological profiles.[1] Other genes critical for hematopoiesis and cell cycle regulation also harbor important variants. CEBPA (CCAAT Enhancer Binding Protein Alpha) is a master transcription factor vital for myeloid cell development, influencing the differentiation of granulocytes and monocytes and the maintenance of hematopoietic stem cell function. Variants such as rs78744187 , rs113244484 , and rs4805870 in the CEBPA region, which also encompasses SLC7A10 (Solute Carrier Family 7 Member 10), may disrupt this intricate process, potentially leading to alterations in white blood cell counts or affecting susceptibility to myeloid disorders.[1] The CDK6 (Cyclin Dependent Kinase 6) gene, a key regulator of cell cycle progression, is essential for the proliferation of hematopoietic stem and progenitor cells. Polymorphisms like rs445 , rs3731332 , and rs111812139 in CDK6can impact cell division rates in the bone marrow, affecting the overall cellularity and specific blood cell populations. Furthermore,TUBB1 (Tubulin Beta 1 Class I) encodes a crucial structural protein for microtubules, which are fundamental for cell shape, movement, and division, particularly in megakaryocytes and platelets.[1] Variants such as rs150072434 , rs34524896 , and rs463312 in TUBB1have been linked to variations in platelet size and count, affecting both the quantity and quality of platelets.
Beyond these core regulators, genes involved in metabolism, mitochondrial function, and protein degradation also contribute to hematological diversity.SMOX (Spermine Oxidase) is involved in polyamine metabolism, a pathway critical for cell growth, differentiation, and survival across various cell types, including those in the blood system. Variants like rs6084653 , rs10531699 , and rs1741318 in SMOX could modify polyamine levels, thereby influencing the proliferation and maturation of blood cell lineages and potentially leading to altered cell counts.[1] PRELID3B (PRELI Domain Containing 3B) is thought to be involved in mitochondrial lipid transfer and cellular metabolism, which are vital for the high metabolic demands of hematopoietic cells. Variants rs141490673 and rs578092393 might subtly influence energy production and cellular health in blood cell precursors. CTSZ(Cathepsin Z), encoding a lysosomal cysteine protease, plays a role in protein turnover and immune responses. Its variants, includingrs56775894 , rs163801 , and rs235202 , may affect the function of immune cells or the degradation of essential proteins within blood cells.[1] Lastly, variants like rs6888037 , rs34145453 , and rs11330548 in SLC12A2-DT (Solute Carrier Family 12 Member 2 Readthrough) may impact the expression or function of SLC12A2, a transporter crucial for cell volume regulation and electrolyte balance, which are processes fundamental for maintaining red blood cell integrity and overall blood health.
Key Variants
Section titled “Key Variants”| RS ID | Gene | Related Traits |
|---|---|---|
| rs62143194 rs62143199 rs3974831 | NLRP12 | interleukin 1 receptor antagonist double-stranded RNA-binding protein Staufen homolog 1 tumor necrosis factor receptor superfamily member 16 inosine-5’-monophosphate dehydrogenase 1 very long-chain acyl-CoA synthetase |
| rs7257867 rs4806509 rs12972849 | NLRP12 - MYADM-AS1 | hematological |
| rs78744187 rs113244484 rs4805870 | SLC7A10 - CEBPA | erythrocyte volume basophil count, eosinophil count basophil count blood protein amount erythrocyte count |
| rs6084653 rs10531699 rs1741318 | SMOX | reticulocyte amount mean reticulocyte volume mean corpuscular hemoglobin concentration erythrocyte volume Red cell distribution width |
| rs150072434 rs34524896 rs463312 | TUBB1 | hematological |
| rs445 rs3731332 rs111812139 | CDK6 | leukocyte quantity eosinophil count neutrophil count, eosinophil count granulocyte count basophil count |
| rs141490673 rs578092393 | PRELID3B | platelet volume hematological |
| rs56775894 rs163801 rs235202 | CTSZ | hematological |
| rs6888037 rs34145453 rs11330548 | SLC12A2-DT | serum alanine aminotransferase amount body fat percentage appendicular lean mass hematocrit type 2 diabetes mellitus |
| rs8103186 rs149287489 rs3859507 | MIR373 - NLRP12 | hematological |
Hematopoiesis and Blood Components
Section titled “Hematopoiesis and Blood Components”The circulatory system relies on a diverse array of cellular and molecular components to maintain its functions, including oxygen transport, immune defense, and hemostasis, the process of stopping bleeding. Hematological phenotypes, therefore, reflect the health and functional capacity of these blood constituents. Key among these are platelets, small anucleated cells derived from megakaryocytes in the bone marrow, which are critical for initiating clot formation. Another crucial component is fibrinogen, a soluble glycoprotein primarily synthesized in the liver, which circulates in the plasma and is essential for the later stages of blood coagulation.[1] These components collectively ensure the dynamic balance of blood fluidity and clot formation, vital for preventing both excessive bleeding and inappropriate clotting within the vasculature.
Molecular Mechanisms of Hemostasis
Section titled “Molecular Mechanisms of Hemostasis”Hemostasis is a tightly regulated process involving complex interactions between blood cells, plasma proteins, and the vessel wall. Platelet aggregation, a central event in primary hemostasis, is triggered by various agonists such as adenosine diphosphate (ADP), collagen, and epinephrine (Epi).[1]Upon activation, platelets undergo shape changes, release their granular contents, and express surface receptors that facilitate their adhesion to the injured vessel wall and to each other, forming a platelet plug. Concurrently, fibrinogen plays a pivotal role in secondary hemostasis by serving as the precursor to fibrin, which forms the structural meshwork of a stable blood clot. This conversion is catalyzed by thrombin, and the resulting fibrin strands stabilize the platelet plug, reinforcing the clot and preventing further blood loss. Disruptions in these intricate molecular and cellular pathways can lead to serious conditions, ranging from bleeding disorders to thrombotic events.
Genetic Architecture of Hematological Phenotypes
Section titled “Genetic Architecture of Hematological Phenotypes”Individual variations in hematological phenotypes are significantly influenced by genetic factors. Genes encode the critical proteins, enzymes, and receptors involved in hematopoiesis, cell function, and hemostatic pathways, establishing a complex regulatory network. Single nucleotide polymorphisms (SNPs) within these genes or their regulatory regions can alter gene expression patterns or protein function, thereby modulating the levels or activity of components like fibrinogen and the responsiveness of platelets.[1]Studies aim to identify specific candidate genes associated with hemostatic factors and platelet aggregation phenotypes, providing insights into the inherited predisposition to variations in blood parameters and related disease risks.[1]Understanding these genetic mechanisms is crucial for elucidating the heritable basis of hematological traits and their potential implications for health.
Systemic Relevance and Pathophysiological Implications
Section titled “Systemic Relevance and Pathophysiological Implications”Hematological phenotypes are not isolated traits but are intricately linked to systemic physiological processes and overall health, serving as important indicators of disease risk and progression. For instance, abnormal levels of hemostatic factors like fibrinogen or altered platelet aggregation responses can significantly increase the risk of cardiovascular disease.[1]Various non-genetic factors also interact with genetic predispositions to influence these phenotypes, including age, sex, body mass index, and lifestyle choices such as current cigarette smoking.[1]These covariates highlight the multifactorial nature of hematological regulation, where environmental exposures and physiological states can modulate the expression of genetic potential, leading to homeostatic disruptions or compensatory responses that impact overall cardiovascular health.
Diagnostic and Monitoring Utility
Section titled “Diagnostic and Monitoring Utility”Hematological measurements, encompassing factors like platelet count, platelet function, and fibrinogen levels, are critical for diagnosing and managing a wide array of clinical conditions. These measurements serve as fundamental indicators of hemostatic balance and overall hematopoietic health. For instance, serial measurements of parameters such as fibrinogen levels can provide valuable insights into disease progression or response to therapeutic interventions over time, as demonstrated in studies assessing these factors across multiple examination cycles.[1] Similarly, comprehensive evaluations of platelet aggregation using various agonists like ADP, collagen, and epinephrine offer a detailed understanding of platelet function, which is essential for diagnosing bleeding disorders or thrombotic tendencies.[1] The identification of novel genetic loci influencing these measurements, even in specific populations like children, enhances our understanding of the underlying biological mechanisms and can refine diagnostic approaches.[2]By integrating genetic predispositions with standard laboratory assays, clinicians can achieve a more nuanced diagnostic picture, particularly in cases with ambiguous presentations or familial history. This integrated approach supports more precise diagnostic classification and the development of targeted monitoring strategies tailored to an individual’s unique hematological profile.
Genetic Contributions to Risk Assessment
Section titled “Genetic Contributions to Risk Assessment”Understanding the genetic underpinnings of hematological measurements is increasingly pivotal for effective risk stratification and the advancement of personalized medicine. Genome-wide studies have identified specific single nucleotide polymorphisms (SNPs) associated with variations in hemostatic factors and hematological phenotypes, such as platelet aggregation and fibrinogen levels.[1] The quantitative impact of these genetic variants, often expressed as a beta coefficient indicating the change in a phenotype per allele increment, allows for the identification of individuals at higher genetic risk for specific conditions.
By accounting for these genetic associations, alongside traditional risk factors like age, sex, body mass index, and prevalent cardiovascular disease, clinicians can develop more precise risk profiles for patients.[1] This genetic information can help differentiate individuals who might benefit from early intervention or more intensive surveillance strategies. While the immediate translation to personalized treatment selection requires further research, these genetic insights lay the groundwork for future tailored therapeutic approaches and preventive measures.
Prognostic Implications and Disease Associations
Section titled “Prognostic Implications and Disease Associations”Variations in hematological measurements carry significant prognostic value, particularly concerning conditions with strong hemostatic components. Abnormal levels of hemostatic factors, such as fibrinogen, or altered platelet function are known to be associated with an increased risk for cardiovascular disease.[1]The systematic analysis of these factors, including their genetic determinants, helps in predicting disease outcomes and assessing the long-term implications for patient health.
Research that adjusts for prevalent cardiovascular disease when examining hemostatic factors underscores the strong link between these hematological parameters and major comorbidities, highlighting their role as potential markers for disease progression.[1]Identifying genetic loci that influence platelet count and function also provides a foundation for understanding inherited predispositions to certain hematological disorders or complications, which can guide long-term management and prognostic counseling. Ultimately, a comprehensive understanding of hematological measurements and their genetic modulators is crucial for predicting clinical trajectories and mitigating adverse health outcomes.
Large-Scale Cohort Studies and Longitudinal Trends
Section titled “Large-Scale Cohort Studies and Longitudinal Trends”Population studies investigating hematological phenotypes frequently leverage large-scale, well-characterized cohorts to understand their prevalence and patterns across diverse groups. Research on white blood cell (WBC) phenotypes, for instance, has utilized a discovery set of seven major cohorts, including the Framingham Heart Study (FHS), the Rotterdam Study (RS), and the NHLBI’s Atherosclerosis Risk in Communities (ARIC) Study, encompassing 19,509 subjects.[3] These foundational cohorts, along with ten replication cohorts such as the Twins UK cohort and various regional European studies, totaling 11,823 subjects, provide substantial statistical power and representativeness for identifying genetic factors influencing these traits.[3] Such extensive data collection adheres to rigorous ethical standards, with all participants providing informed consent and studies conducted in accordance with the Declaration of Helsinki.[3]Longitudinal designs within these large cohorts are critical for observing temporal patterns and the evolution of hematological characteristics over time. The Framingham Heart Study, for example, has conducted serial assessments of hemostatic factors like fibrinogen across multiple examination cycles (5, 6, and 7) in its Offspring cohort.[1]This approach allows researchers to track changes in these phenotypes, providing insights into their stability, progression, and potential associations with health outcomes across different life stages. By collecting data repeatedly from the same individuals, these studies offer a powerful means to distinguish between transient fluctuations and sustained alterations in hematological characteristics, which is vital for understanding disease risk and progression.
Genetic Epidemiology and Population Diversity
Section titled “Genetic Epidemiology and Population Diversity”Genetic epidemiology plays a crucial role in elucidating the underlying determinants of hematological phenotypes, with large-scale genome-wide association studies (GWAS) frequently employed across diverse populations. Studies have sought to identify genetic loci associated with variations in white blood cell counts, utilizing combined discovery and replication cohorts that represent a broad spectrum of European populations, including those from the Netherlands, the United States, Iceland, Italy, and the United Kingdom.[3] This multinational approach helps to capture a wider range of genetic diversity and assess the generalizability of genetic associations across different ethnic and geographic groups, even as the primary goal is often to understand variation within such populations.[3]Beyond general blood cell counts, specific hemostatic factors and platelet characteristics have also been subjected to intensive genetic investigation. For instance, the Framingham Heart Study has conducted genome-wide association and linkage analyses to identify single nucleotide polymorphisms (SNPs) associated with hemostatic factors, such as fibrinogen levels, and various platelet aggregation phenotypes.[1]These analyses typically involve examining a large number of SNPs within or near previously implicated candidate genes, providing a comprehensive scan for genetic influences on complex hematological traits.[1]Such studies contribute to understanding the prevalence patterns of specific genetic variants and their impact on normal physiological ranges and disease susceptibility across populations.
Methodological Approaches and Epidemiological Associations
Section titled “Methodological Approaches and Epidemiological Associations”The robust methodologies employed in population studies of hematological phenotypes are fundamental to ensuring the reliability and generalizability of findings. Typical study designs involve large-scale cohort studies, often with thousands of participants, such as the 19,509 individuals in the discovery phase and 11,823 in the replication phase of studies on white blood cell phenotypes.[3] These investigations often involve genome-wide association and linkage analyses, where a vast number of SNPs are screened for association with the phenotype.[1]To account for potential confounding, statistical models commonly adjust for key demographic and clinical factors, including age, sex, body mass index, prevalent cardiovascular disease, and current cigarette use, which are known correlates of many hematological traits.[1]Beyond identifying genetic associations, epidemiological studies aim to delineate the patterns of hematological characteristics within populations and their links to broader health indicators. By adjusting for demographic factors like age and sex, researchers can better understand how these fundamental attributes influence the distribution and typical ranges of hematological phenotypes. Furthermore, controlling for health-related covariates such as body mass index and cardiovascular disease helps to isolate the specific effects of genetic variants or other exposures from established clinical risk factors.[1]The careful consideration of these epidemiological associations and methodological adjustments ensures that the identified genetic and environmental influences on hematological traits are interpreted within the appropriate population context, enhancing the relevance of findings for public health and personalized medicine.
Frequently Asked Questions About Hematological
Section titled “Frequently Asked Questions About Hematological”These questions address the most important and specific aspects of hematological based on current genetic research.
1. My parents have blood issues; will I get them too?
Section titled “1. My parents have blood issues; will I get them too?”Yes, your genetic makeup significantly influences your blood traits. Genes like _HBB_, _HBD_, _HBG1_, _HBG2_, and _HBE1_, involved in hemoglobin synthesis, are known to affect blood measurements like hematocrit, meaning you can inherit predispositions.
2. I’m not Caucasian; does my background affect my blood tests?
Section titled “2. I’m not Caucasian; does my background affect my blood tests?”Yes, research shows that findings from studies primarily on one ancestry may not apply to others. Differences in genetic architecture and allele frequencies across diverse populations can influence your normal blood ranges and disease risk.
3. Can what I eat or do actually affect my blood count?
Section titled “3. Can what I eat or do actually affect my blood count?”Absolutely. Environmental factors like your lifestyle, diet, and even infections are powerful influences. They can modify how your genetic predispositions express, significantly impacting your blood parameters.
4. Does getting older mean my blood numbers will always change?
Section titled “4. Does getting older mean my blood numbers will always change?”Yes, age is a known factor that influences hematological traits. Researchers often adjust for age in studies because it can naturally lead to variations in blood measurements over time.
5. I feel tired all the time; could it be my blood?
Section titled “5. I feel tired all the time; could it be my blood?”Yes, persistent fatigue can be a sign of underlying blood issues. Deviations from normal blood ranges, such as low red blood cell count (anemia), are common causes for feeling tired and can be detected by blood tests.
6. Why is my friend’s blood count always perfect, but mine isn’t?
Section titled “6. Why is my friend’s blood count always perfect, but mine isn’t?”Individual differences in your genetic pathways, which control blood cell production, can explain this. Genetic variations, even in specific SNPs like *rs10488676 * or *rs10499199 *, contribute to variations in blood traits among people.
7. Could a DNA test tell me if I’m at risk for blood problems?
Section titled “7. Could a DNA test tell me if I’m at risk for blood problems?”Yes, understanding the genetic determinants of blood traits through studies like genome-wide association analyses can lead to more personalized medicine approaches. This can improve diagnostic accuracy and identify your specific risks for blood disorders.
8. If blood issues run in my family, can I still do something about it?
Section titled “8. If blood issues run in my family, can I still do something about it?”Yes, while genetics play a significant role, environmental factors are also powerful influences. Your lifestyle, diet, and managing external exposures can modify the expression of genetic predispositions and support better blood health.
9. Does being really stressed or sick mess with my blood results?
Section titled “9. Does being really stressed or sick mess with my blood results?”Yes, external factors like infections and other exposures can significantly influence your blood parameters. These environmental influences can modify how your genetic predispositions are expressed.
10. Why do doctors always want me to get a blood test?
Section titled “10. Why do doctors always want me to get a blood test?”Regular blood tests, including complete blood counts, are fundamental tools in preventive healthcare. They allow clinicians to detect early signs of a wide range of conditions and tailor treatment strategies.
This FAQ was automatically generated based on current genetic research and may be updated as new information becomes available.
Disclaimer: This information is for educational purposes only and should not be used as a substitute for professional medical advice. Always consult with a healthcare provider for personalized medical guidance.
References
Section titled “References”[1] Yang Q et al. Genome-wide association and linkage analyses of hemostatic factors and hematological phenotypes in the Framingham Heart Study. BMC Med Genet. 2007; 8.
[2] Guerrero JA et al. Novel loci involved in platelet function and platelet count identified by a genome-wide study performed in children. Haematologica. 2011; 96(9).
[3] Nalls, M. A., et al. “Multiple loci are associated with white blood cell phenotypes.” PLoS Genet, vol. 7, no. 7, 2011.
[4] Reiner, A. P., et al. “Genome-wide association study of white blood cell count in 16,388 African Americans: the continental origins and genetic epidemiology network (COGENT).” PLoS Genet, vol. 7, no. 7, 2011.