Serotransferrin
Serotransferrin, commonly referred to as transferrin, is a vital glycoprotein in human blood plasma responsible for the transport of iron throughout the body. It is the primary iron-binding protein, playing a crucial role in delivering iron from absorption sites in the intestine and from storage cells to all tissues that require it for metabolic processes, such as erythropoiesis (red blood cell production) and cellular respiration. Understanding serotransferrin levels is important for assessing iron status and diagnosing various health conditions[1].
Biological Basis
Section titled “Biological Basis”The biological function of serotransferrin is centered on its high affinity for iron ions, allowing it to safely sequester and transport iron, preventing its toxic accumulation in free form. Serotransferrin is synthesized predominantly in the liver. Its production is influenced by the body’s iron stores; generally, serotransferrin levels increase when iron stores are low and decrease when iron stores are high. Genetic factors play a significant role in determining an individual’s serotransferrin levels. Studies have shown that variants in genes such asTF (encoding transferrin itself) and HFE (involved in iron homeostasis) collectively explain approximately 40% of the genetic variation observed in serum-transferrin levels [1]. The SRPRB gene, which encodes a signal-recognition particle receptor required for targeting secreted proteins like serum transferrin, has also been identified as influencing serum-transferrin concentration [1].
Clinical Relevance
Section titled “Clinical Relevance”Measuring serotransferrin levels is a standard diagnostic tool in clinical practice, primarily used to evaluate iron metabolism and diagnose conditions related to iron deficiency or overload. Abnormal serotransferrin levels can indicate various health issues, including iron deficiency anemia (often characterized by high transferrin levels as the body attempts to maximize iron uptake), chronic inflammation, liver disease, and genetic disorders of iron metabolism such as hemochromatosis. Serotransferrin levels, often considered an intermediate phenotype, provide valuable insights into underlying physiological pathways. Genome-wide association studies (GWAS) frequently investigate such continuous-scale intermediate phenotypes to better understand the genetic architecture of complex traits and their connections to disease[2].
Social Importance
Section titled “Social Importance”The widespread prevalence of iron-related disorders, such as iron deficiency anemia, highlights the social importance of understanding serotransferrin levels. Iron deficiency affects a significant portion of the global population, particularly women and children, leading to fatigue, impaired cognitive function, and reduced work productivity. Conversely, iron overload, as seen in conditions like hemochromatosis, can lead to severe organ damage if not managed. By identifying the genetic variants that influence serotransferrin levels, researchers can improve risk prediction, facilitate earlier diagnosis, and potentially develop more targeted therapeutic strategies for individuals at risk of iron-related health problems. Such genetic insights contribute to the broader goal of personalized medicine, where treatments can be tailored based on an individual’s genetic predisposition to maintain optimal iron balance and overall health.
Limitations
Section titled “Limitations”Methodological and Statistical Constraints
Section titled “Methodological and Statistical Constraints”Research into serotransferrin levels faces several methodological and statistical limitations that impact the comprehensiveness and generalizability of findings. Many studies, particularly early genome-wide association studies (GWAS), were designed to avoid compounding multiple testing issues, often leading to sex-pooled analyses that might overlook genetic variants associated with serotransferrin exclusively in males or females[3]. Furthermore, while GWAS offers an unbiased approach to discovering novel genes, the reliance on a subset of available single nucleotide polymorphisms (SNPs) can result in incomplete genomic coverage, potentially missing relevant genes or failing to comprehensively characterize candidate genes [3]. The accurate estimation of effect sizes and the proportion of variance explained also requires careful consideration, especially when studies utilize averaged observations from repeated measurements or monozygotic twin pairs, which can introduce specific statistical nuances [1].
Replication of genetic associations, a cornerstone of robust scientific discovery, also presents challenges in serotransferrin research. Non-replication of specific SNP associations across studies can occur even when different SNPs within the same gene are strongly linked to the trait, suggesting multiple causal variants or variations in linkage disequilibrium patterns across populations[4]. Discrepancies in study power, cohort characteristics, and overall study design further contribute to observed differences in replication rates, making it crucial to interpret findings within the context of these methodological variations [4]. These factors collectively highlight the need for larger, more diverse, and meticulously designed studies to fully capture the genetic architecture influencing serotransferrin levels.
Population Specificity and Phenotypic Characterization
Section titled “Population Specificity and Phenotypic Characterization”The generalizability of genetic findings for serotransferrin is often constrained by the population characteristics of the study cohorts. While some studies employ family-based association tests robust to population admixture, and others demonstrate minimal residual population stratification effects, many large-scale genetic investigations predominantly feature individuals of European descent[5]. This demographic imbalance can limit the applicability of identified genetic variants and their effect sizes to other ancestral groups, where different allele frequencies or genetic architectures may exist. Consequently, translating these findings into personalized health care or nutrition strategies for diverse global populations requires further research across varied ancestries [2].
Moreover, the precise phenotypic characterization of serotransferrin levels is crucial, and variability in measurement protocols or the influence of environmental factors can introduce confounding. Studies often adjust for known covariates such as age, smoking status, body mass index, hormone therapy use, and menopausal status to isolate genetic effects[6]. However, other unmeasured environmental factors, lifestyle choices, or underlying health conditions could still influence serotransferrin levels, potentially obscuring or modulating genetic associations. A comprehensive understanding requires integrating detailed environmental and lifestyle data alongside genetic information to account for these complex influences.
Unexplained Genetic Variation and Complex Influences
Section titled “Unexplained Genetic Variation and Complex Influences”Despite significant advancements in identifying genetic loci associated with serotransferrin, a substantial portion of its heritability remains unexplained, a phenomenon often referred to as “missing heritability.” While variants in genes like TF and HFE have been shown to account for approximately 40% of the genetic variation in serotransferrin levels, this still leaves a considerable proportion attributed to unknown genetic or environmental factors[1]. This unexplained variation suggests the involvement of rarer genetic variants, structural genomic changes, or complex gene-gene and gene-environment interactions that are not fully captured by current genome-wide association studies.
The identification of these interacting factors is essential for a complete understanding of the biological pathways that regulate serotransferrin and its role in human health. Current research provides a foundational step toward understanding these pathways, yet more detailed investigations are needed to unravel the intricate network of genetic and environmental influences[2]. Addressing this missing heritability and exploring the dynamic interplay between genetic predispositions and environmental exposures will be critical for developing more precise predictive models and targeted interventions related to serotransferrin.
Variants
Section titled “Variants”Genetic variations play a significant role in determining an individual’s serotransferrin levels, a key indicator of iron status. Many of these variants are found in genes directly involved in iron transport and regulation, while others influence broader cellular processes that indirectly impact iron homeostasis. Understanding these genetic influences provides insight into an individual’s predisposition to certain iron-related conditions and their physiological iron metabolism.
The Transferrin (TF) gene and the HFE gene are central to iron metabolism, and variants within them collectively explain a substantial portion of the genetic variation in serum transferrin levels. Transferrin, encoded by the TF gene, is the primary protein responsible for transporting iron in the blood, ensuring its delivery to cells throughout the body. Specific TF variants, such as rs3811647 , rs1799852 , and rs2280673 , have been identified as independently influencing serum transferrin concentrations, with rs3811647 alone accounting for a significant percentage of this variation [1]. These variants can alter the protein’s efficiency or expression, affecting how much iron is carried. The HFE gene, on the other hand, is crucial for regulating dietary iron absorption. The well-known C282Y mutation in HFE (rs1800562 ) is strongly associated with levels of serum iron, serum transferrin, transferrin saturation, and serum ferritin [1]. Together, variants in TF, including rs1525892 , rs187267468 , rs145241425 , and rs8177252 , along with HFE variants like rs79220007 , are estimated to account for approximately 40% of the genetic variation in circulating serotransferrin[1].
The Signal Recognition Particle Receptor B (SRPRB) gene also plays a critical role in the proper processing and secretion of proteins like transferrin. Located in close proximity to the TF gene, SRPRB encodes a receptor essential for guiding newly synthesized secreted proteins to the endoplasmic reticulum [1]. Variants in SRPRB, such as rs10512913 mentioned in studies, are linked to both SRPRB mRNA expression and serum-transferrin concentration, indicating that variations in SRPRB’s function can directly influence the amount of transferrin available in the blood [1]. This highlights the importance of the cellular machinery responsible for protein trafficking in maintaining circulating transferrin levels. Other variants in SRPRB, including rs184838825 and rs76497943 , may similarly impact the efficiency of transferrin secretion. Additionally, the RAB6B gene, with variants like rs17376530 , rs112621868 , and rs2370637 , contributes to intracellular vesicle trafficking, a fundamental process for protein secretion, thereby potentially influencing serotransferrin levels through its role in the secretory pathway.
Beyond these more direct influences, other genetic loci contribute to the broader regulation of iron homeostasis and related physiological functions. The rs8177252 variant, associated with both TF and ACSL3P1 (Acyl-CoA Synthetase Long-Chain Family Member 3 Pseudogene 1), suggests a potential interplay between lipid metabolism and iron transport pathways, given ACSL3P1’s role in fatty acid metabolism and TF’s central function in iron delivery [1]. The region encompassing KDM3AP1 (Lysine Demethylase 3A Pseudogene 1) and SLC40A1 (Solute Carrier Family 40 Member 1), including variant rs13008704 , is highly relevant because SLC40A1, also known as ferroportin, is the sole known protein responsible for exporting iron from cells into the bloodstream, making it critical for systemic iron balance [1]. Other genes like H2BC4 (Histone H2B Type 1-4) with variant rs79220007 , TSBP1-AS1 (Testis-Specific Basic Protein 1 Antisense RNA 1) and TSBP1 (Testis-Specific Basic Protein 1) with rs9268247 , and CDV3 (Cell Division Cycle Associated 3) with rs142948478 may indirectly modulate cellular processes, gene expression, or metabolic activity that intersect with iron regulation. Furthermore, SLCO2A1 (Solute Carrier Organic Anion Transporter Family Member 2A1) and its variant rs7427580 could affect systemic inflammation or prostaglandin transport, which are known to influence iron status. These variants, through diverse mechanisms, collectively shape the complex network that governs the body’s iron status and circulating serotransferrin levels.
Key Variants
Section titled “Key Variants”| RS ID | Gene | Related Traits |
|---|---|---|
| rs79220007 | H2BC4, HFE | mean corpuscular hemoglobin concentration reticulocyte count Red cell distribution width osteoarthritis, hip platelet count |
| rs184838825 | TF, SRPRB | serotransferrin measurement |
| rs76497943 | SRPRB | serotransferrin measurement |
| rs9268247 | TSBP1-AS1, TSBP1 | clostridiales seropositivity serotransferrin measurement uromodulin measurement linoleic acid measurement polyunsaturated fatty acid measurement |
| rs17376530 rs112621868 rs2370637 | RAB6B | serotransferrin measurement |
| rs1525892 rs187267468 rs145241425 | TF | acute myeloid leukemia mean corpuscular hemoglobin concentration serotransferrin measurement |
| rs142948478 | CDV3 | serotransferrin measurement |
| rs8177252 | TF, ACSL3P1 | blood protein amount serotransferrin measurement serum iron amount |
| rs7427580 | SLCO2A1 | serotransferrin measurement |
| rs13008704 | KDM3AP1 - SLC40A1 | serotransferrin measurement mean corpuscular hemoglobin |
Definition and Biological Role of Serotransferrin
Section titled “Definition and Biological Role of Serotransferrin”Serotransferrin, commonly referred to as serum transferrin, is a crucial biomarker trait found in human serum[7]. This iron-binding glycoprotein plays a fundamental role in systemic iron metabolism, acting as the primary transporter of iron through the bloodstream to various tissues throughout the body. As an intermediate phenotype, serotransferrin levels are recognized for their capacity to offer detailed insights into potentially affected biological pathways, thereby enhancing the understanding of complex physiological processes[2]. Its precise measurement is therefore integral for assessing an individual’s iron status and for diagnosing conditions related to iron dysregulation.
Measurement and Operational Definitions
Section titled “Measurement and Operational Definitions”The operational definition of serotransferrin involves its quantitative assessment in serum samples, with concentrations typically reported in grams per liter (g/L)[1]. For example, research studies have established mean serum transferrin levels, such as 5.30 g/L for females within specific cohorts [1]. Complementing this, transferrin saturation is another key metric, expressed as a percentage, which indicates the proportion of transferrin molecules bound to iron; a reported mean for this in females is 24.15% [1].
Measurement approaches for serotransferrin can encompass a variety of methods utilized by clinical and research laboratories. While specific techniques for serotransferrin are not explicitly detailed, similar biomarker quantifications in the same context have been performed using methodologies such as spectrophotometry and colorimetric assays by specialized diagnostic providers like Quest Diagnostics (formerly METPATH)[7]. The use of such diverse, yet standardized, biochemical assays ensures consistent and reliable data collection, which is vital for large-scale genetic and metabolic studies.
Classification and Clinical Significance
Section titled “Classification and Clinical Significance”Serotransferrin is primarily classified as a continuous quantitative trait, implying that its levels exist along a spectrum rather than in discrete categories[2]. This dimensional approach allows for a more nuanced evaluation of iron status and its implications for metabolic health, moving beyond simple presence or absence of a condition. The measurement of both serotransferrin and transferrin saturation acts as a biomarker, providing valuable information about an individual’s capacity for iron transport and overall iron homeostasis[7].
Within a broader conceptual framework, serotransferrin levels are viewed as an intermediate phenotype, reflecting the intricate interplay between genetic predispositions and environmental factors that influence metabolic pathways[2]. Genetic studies have notably identified common variants in genes such as TF and HFE that account for a significant portion, approximately 40%, of the genetic variation observed in serum transferrin levels [1]. This understanding of both the genetic underpinnings and the continuous nature of serotransferrin contributes significantly to the development of personalized health care and nutrition strategies, integrating both an individual’s genotype and their metabolic characteristics[2].
Serotransferrin’s Fundamental Role and Molecular Identity
Section titled “Serotransferrin’s Fundamental Role and Molecular Identity”Serotransferrin is a vital secreted protein found circulating in human serum, playing a critical role in systemic biology. As a key biomolecule, its presence and concentration are indicative of underlying physiological states. The proper cellular function of secreting proteins like serotransferrin into the bloodstream is a complex process, which relies on specific molecular machinery, including the signal-recognition particle receptor B subunit (SRPRB) . This significant genetic influence underscores the inherent biological variability of serotransferrin levels, which is vital for clinical interpretation.
Furthermore, a specific single nucleotide polymorphism (SNP), rs10512913 , located in the SRPRB gene, has been associated with both serum transferrin concentration and the expression of SRPRB messenger RNA (mRNA) [1]. This finding suggests a potential mechanistic link between SRPRBgene activity and serotransferrin levels. Understanding these genetic determinants is paramount for accurately interpreting serotransferrin measurements when used as a biomarker, particularly in the comprehensive assessment of iron status, where it is often evaluated alongside transferrin saturation and serum ferritin[1].
Risk Stratification and Personalized Medicine
Section titled “Risk Stratification and Personalized Medicine”The significant genetic component influencing serotransferrin levels highlights its potential utility in risk stratification and the development of personalized medicine approaches. Identifying individuals with specific genetic variants that predispose them to altered serotransferrin concentrations could enable more targeted health interventions[1]. For instance, genetic profiling could help pinpoint individuals who might be at a higher risk for conditions related to iron dysregulation, thereby guiding tailored screening protocols or preventative strategies before overt symptoms appear.
While the complexities of genetic analyses, including the need for stringent statistical corrections for multiple comparisons, are acknowledged in genetic studies, the robust identification of genetic determinants for serotransferrin points towards future applications in individualized patient care[1]. Integrating such genetic information with metabolic characterization holds promise for advancing personalized health care and nutrition strategies [2].
Prognostic Value and Clinical Monitoring
Section titled “Prognostic Value and Clinical Monitoring”Given its fundamental role in iron homeostasis, the measurement of serotransferrin levels carries potential prognostic value, although current research primarily elucidates its genetic underpinnings rather than direct prognostic outcomes. Variations in serotransferrin concentrations, whether influenced by genetic factors or acquired conditions, could potentially serve as indicators for disease progression or responsiveness to treatment in disorders involving iron dysregulation[1].
Leveraging the understanding of the genetic basis of these variations, as demonstrated by the impact of TF and HFE variants, could lead to the development of more refined clinical monitoring strategies. Such insights may aid in predicting long-term implications for patient health and guiding therapeutic decisions [1]. However, further dedicated research is essential to fully establish the prognostic utility of serotransferrin levels across diverse patient populations and in specific clinical contexts.
Population Studies
Section titled “Population Studies”Genetic Architecture and Large-scale Cohort Investigations
Section titled “Genetic Architecture and Large-scale Cohort Investigations”Population studies have extensively utilized large-scale cohorts and advanced genomic techniques, such as genome-wide association studies (GWAS), to unravel the genetic architecture influencing serum transferrin levels. Research involving major population cohorts has identified significant genetic determinants, with variants in the TF (transferrin) and HFE genes collectively explaining a substantial portion, approximately 40%, of the genetic variation observed in serum transferrin levels [1]. These findings underscore a strong inherited component to serum transferrin concentrations. Such investigations, including those focused on protein quantitative trait loci (pQTLs), have systematically mapped genetic regions associated with serum transferrin, often drawing from diverse populations to ensure broad discovery [8].
Further insights into the genetic underpinnings of serum transferrin have emerged from studies in specific populations, such as birth cohorts within founder populations. For instance, genome-wide association analyses of metabolic traits in a Finnish birth cohort have contributed to understanding how genetic factors in distinct demographic groups influence serum transferrin and related metabolic markers [4]. These large-scale studies frequently employ sophisticated methodologies, including targeted metabolite profiling by electrospray ionization tandem mass spectrometry (ESI-MS/MS), to accurately quantify serum components and ensure high-quality data for genetic association analyses [2]. The integration of genetic data with detailed biochemical measurements across vast participant numbers provides a robust framework for identifying core genetic drivers of serum transferrin levels.
Cross-Population Variability and Epidemiological Associations
Section titled “Cross-Population Variability and Epidemiological Associations”The examination of serum transferrin levels across different populations reveals important insights into demographic and geographic variations, highlighting the need for cross-population comparisons. Studies involving multiple European population cohorts, for example, contribute to understanding the spectrum of serum transferrin levels and their genetic influences within a broad European context [5]. While specific details on prevalence patterns or incidence rates of altered serum transferrin levels are not extensively detailed in all studies, the identification of genetic variants contributing to its variability implies potential differences in these epidemiological parameters across populations with varying genetic ancestries.
Research efforts often involve extensive international collaborations, spanning institutions across the United States, the United Kingdom, Italy, and Finland, which facilitates the study of serum transferrin in ethnically diverse groups [8]. Such collaborative undertakings are crucial for identifying population-specific effects and assessing the generalizability of genetic associations found in one group to another. For example, the detailed analysis of serum transferrin in female monozygotic twin pairs from Australia, alongside contributions from Finnish and UK institutions, provides a unique perspective on both genetic and environmental influences on this biomarker within specific demographic strata [1]. These studies begin to lay the groundwork for understanding how demographic factors and geographical origins might shape serum transferrin distribution at a population level.
Methodological Approaches and Generalizability Considerations
Section titled “Methodological Approaches and Generalizability Considerations”The robust methodologies employed in population studies of serum transferrin are critical for generating reliable and generalizable findings. Genome-wide association studies (GWAS) are a cornerstone of this research, meticulously designed to identify genetic loci associated with quantitative traits like serum transferrin levels [1]. These studies often involve very large sample sizes, sometimes encompassing thousands of individuals across multiple cohorts, to achieve sufficient statistical power for detecting subtle genetic effects. The rigorous processes for sample collection, such as standardized serum preparation protocols that include coagulation, centrifugation, and deep freezing, are essential for maintaining sample integrity and ensuring the accuracy of metabolite measurements [2].
However, the representativeness and generalizability of findings require careful consideration. While large multi-ethnic or multi-national cohorts enhance the applicability of results, studies focusing on founder populations, like the Finnish birth cohort, provide valuable insights into specific genetic architectures but may have limited direct generalizability to more admixed populations [4]. Researchers often adjust for demographic factors such as age, smoking status, body-mass index, hormone-therapy use, and menopausal status to minimize confounding and ensure that observed associations are robust [6]. The careful documentation of study designs, participant characteristics, and analytical adjustments is paramount for interpreting the population-level implications of serum transferrin research.
Frequently Asked Questions About Serotransferrin Measurement
Section titled “Frequently Asked Questions About Serotransferrin Measurement”These questions address the most important and specific aspects of serotransferrin measurement based on current genetic research.
1. My family has iron problems; will I get them too?
Section titled “1. My family has iron problems; will I get them too?”Yes, your family history can play a big role in your iron levels. Genes like TF and HFEare known to significantly influence how your body handles iron, explaining about 40% of the natural differences in iron-carrying proteins like serotransferrin. If these genes run in your family, you might have a higher risk for similar iron imbalances.
2. Why am I tired even when I eat lots of iron?
Section titled “2. Why am I tired even when I eat lots of iron?”Feeling tired even with an iron-rich diet can be a sign of iron deficiency anemia, where your body struggles to get enough iron to your tissues. Your body might increase its production of serotransferrin, the protein that carries iron, to try and maximize uptake. This suggests an underlying issue, possibly genetic, affecting how your body processes or utilizes the iron you consume.
3. I’m a woman; am I more likely to have iron issues?
Section titled “3. I’m a woman; am I more likely to have iron issues?”Yes, iron deficiency is more prevalent in women and children globally. While genetics certainly influence your individual serotransferrin levels, factors like menstruation and pregnancy increase iron requirements, making women generally more susceptible to iron deficiency anemia.
4. Does my ethnic background change my iron risk?
Section titled “4. Does my ethnic background change my iron risk?”It can. Many large genetic studies primarily focus on people of European descent, meaning the specific genetic variants and their effects might differ in other ancestral groups. Your ethnic background could mean you have different allele frequencies or genetic architectures that influence your unique iron metabolism and risk.
5. Why do some people naturally get too much iron?
Section titled “5. Why do some people naturally get too much iron?”Some people have a genetic predisposition to iron overload, a condition called hemochromatosis. This is often linked to variants in genes like HFE, which affect how your body regulates iron absorption. When iron stores are high, your body typically decreases serotransferrin production, but the underlying genetic issue can still lead to harmful accumulation.
6. Does getting older affect how my body uses iron?
Section titled “6. Does getting older affect how my body uses iron?”Yes, age is one of the factors that can influence your serotransferrin levels and overall iron metabolism. While genetics set a baseline, your body’s processes change over time. Studies often adjust for age to understand genetic effects better, but it’s clear that aging can be an important consideration for your iron health.
7. I have chronic inflammation; does that affect my iron levels?
Section titled “7. I have chronic inflammation; does that affect my iron levels?”Yes, chronic inflammation can significantly impact your iron levels. Conditions with ongoing inflammation can lead to what’s known as “anemia of chronic disease,” where your body’s transferrin levels might be lower, and iron is sequestered, making it less available for red blood cell production even if stores are present.
8. Can my lifestyle habits mess up my body’s iron balance?
Section titled “8. Can my lifestyle habits mess up my body’s iron balance?”Absolutely. While genetics lay a foundation for your serotransferrin levels, lifestyle choices like smoking status and body mass index are known to influence them. Other unmeasured environmental factors and daily habits can also play a role, either obscuring or modulating your underlying genetic predispositions for iron balance.
9. My liver health isn’t great; can that affect my iron?
Section titled “9. My liver health isn’t great; can that affect my iron?”Yes, definitely. Serotransferrin is primarily synthesized in your liver, so if your liver isn’t functioning optimally due to disease, its ability to produce this vital iron-transporting protein can be impaired. This can directly affect your body’s capacity to manage and distribute iron properly.
10. Could a DNA test predict my personal iron risks?
Section titled “10. Could a DNA test predict my personal iron risks?”Yes, genetic insights are increasingly used for personalized medicine. By identifying variants in genes like TF and HFEthat influence serotransferrin levels, a DNA test could help predict your risk for iron-related health problems like iron deficiency or overload. This can lead to earlier diagnosis and more targeted health strategies for you.
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] Benyamin B, et al. “Variants in TF and HFE Explain Approximately 40% of Genetic Variation in Serum-Transferrin Levels.” The American Journal of Human Genetics, vol. 84, no. 1, 2009, pp. 60–65.
[2] Gieger C, et al. “Genetics Meets Metabolomics: A Genome-Wide Association Study of Metabolite Profiles in Human Serum.” PLoS Genetics, vol. 4, no. 11, 2008, e1000282.
[3] Yang, Qiong, et al. “Genome-Wide Association and Linkage Analyses of Hemostatic Factors and Hematological Phenotypes in the Framingham Heart Study.” BMC Medical Genetics, vol. 8, suppl. 1, 2007, p. S4.
[4] Sabatti, C., et al. “Genome-Wide Association Analysis of Metabolic Traits in a Birth Cohort from a Founder Population.” Nature Genetics, vol. 40, no. 12, Dec. 2008, pp. 1391–98.
[5] Aulchenko, Y. S., et al. “Loci Influencing Lipid Levels and Coronary Heart Disease Risk in 16 European Population Cohorts.”Nature Genetics, vol. 40, no. 12, Dec. 2008, pp. 1410–21.
[6] Ridker, P. M., et al. “Loci Related to Metabolic-Syndrome Pathways Including LEPR, HNF1A, IL6R, and GCKR Associate with Plasma C-Reactive Protein: The Women’s Genome Health Study.” The American Journal of Human Genetics, vol. 82, no. 5, May 2008, pp. 1185–92.
[7] Benjamin EJ, et al. “Genome-wide association with select biomarker traits in the Framingham Heart Study.” BMC Medical Genetics, vol. 8, suppl. 1, 2007.
[8] Melzer, D., et al. “A Genome-Wide Association Study Identifies Protein Quantitative Trait Loci (pQTLs).” PLoS Genetics, vol. 4, no. 5, May 2008, p. e1000072.