Antimigraine Preparation Use
Introduction
Section titled “Introduction”Migraine is a debilitating neurological disorder characterized by severe headaches, often accompanied by symptoms such as pulsating pain, nausea, vomiting, and sensitivity to light and sound. It significantly impacts the quality of life for millions worldwide and poses a substantial public health burden. Antimigraine preparations encompass a wide array of pharmacological treatments designed to alleviate migraine symptoms or prevent their occurrence. Understanding the patterns and efficacy of antimigraine preparation use is crucial for optimizing patient care and public health strategies.
Biological Basis
Section titled “Biological Basis”The underlying biological mechanisms of migraine are complex, involving neuronal hyperexcitability, neurotransmitter dysregulation, and activation of the trigeminal pain pathway. Antimigraine preparations target various aspects of this pathophysiology. For instance, triptans act as serotonin receptor agonists, constricting dilated blood vessels in the brain and inhibiting pain signal transmission. Other treatments may modulate calcitonin gene-related peptide (CGRP) pathways or reduce inflammation. Genetic variations among individuals can significantly influence how these preparations are metabolized and how effectively they interact with their biological targets. Population-based genome-wide association studies (GWAS) have been instrumental in identifying genetic loci associated with various physiological traits, including plasma levels of liver enzymes.[1] and lipid levels.[2], [3], [4] Such genetic insights are derived from analyses that often involve SNP imputation based on large genomic datasets.[1], [5] These genetic factors can affect drug absorption, distribution, metabolism (e.g., via liver enzymes), and excretion, ultimately influencing drug efficacy and the likelihood of adverse effects. Thus, an individual’s genetic profile can play a role in their response to specific antimigraine preparations.
Clinical Relevance
Section titled “Clinical Relevance”Measuring antimigraine preparation use provides vital information for clinical practice. It allows healthcare providers to assess treatment adherence, evaluate the effectiveness of different therapeutic strategies, and identify potential overuse or misuse that could lead to medication overuse headache. Data on preparation use can inform personalized medicine approaches, where an individual’s genetic predisposition or metabolic profile might guide the selection of the most appropriate drug. Monitoring use also helps in understanding real-world treatment outcomes, identifying gaps in care, and informing the development of new, more effective therapies.
Social Importance
Section titled “Social Importance”From a societal perspective, understanding antimigraine preparation use is critical for public health policy and resource allocation. Migraine imposes a significant economic burden due to lost productivity, healthcare costs, and diminished quality of life. Effective management of migraine, facilitated by appropriate use of preparations, can reduce this burden. By analyzing patterns of use across populations, researchers and policymakers can identify disparities in access to care, evaluate the impact of public health campaigns, and develop strategies to improve overall migraine management, thereby enhancing the well-being and productivity of affected individuals.
Methodological and Statistical Constraints
Section titled “Methodological and Statistical Constraints”Research on antimigraine preparation use is often constrained by cohort size, which can limit the statistical power to detect genetic associations, particularly for variants with modest effects.[6] Moderate sample sizes can lead to false negative findings, where true associations remain undetected, thereby underestimating the full genetic contribution to the trait.[6] Furthermore, the necessity to perform sex-pooled analyses to avoid exacerbating multiple testing issues may obscure sex-specific genetic effects, meaning some relevant associations in either males or females could be missed.[7] Replication of identified genetic associations across different studies remains a significant challenge, with a substantial portion of initial findings failing to be replicated.[6] This non-replication can stem from various factors, including initial false positive findings, differences in study design, or inadequate statistical power in replication cohorts.[6] Additionally, reliance on imputation based on reference panels like HapMap, and the use of specific quality control thresholds for imputed SNPs, means that some genetic variants may be missed due to incomplete coverage or stringent filtering, limiting the comprehensiveness of the genetic scan.[1]
Generalizability and Phenotypic Specificity
Section titled “Generalizability and Phenotypic Specificity”A primary limitation in understanding antimigraine preparation use is the restricted generalizability of findings, as many cohorts are predominantly composed of individuals of specific ancestries, often of European descent.[6] This demographic homogeneity means that genetic associations identified may not be directly applicable to populations with different genetic backgrounds or environmental exposures, hindering a universal understanding of the trait.[6] Additionally, selection biases, such as those introduced by studying largely middle-aged to elderly populations or by DNA collection at later examinations, can introduce survival bias and further limit the applicability of results to younger or broader populations.[6]The definition and assessment of complex phenotypes, such as antimigraine preparation use, can vary across studies, contributing to discrepancies and challenges in meta-analyses. Differences in diagnostic criteria, assessment methods, or the specific preparations considered can introduce heterogeneity that complicates the interpretation of combined results.[5] While some studies implement rigorous quality control for biomarker phenotypes, the nuanced nature of self-reported or clinically determined preparation use means that subtle variations in phenotype capture could lead to different genetic signals across cohorts.[6] This variability can obscure true genetic effects or lead to the identification of associations that are specific to a particular phenotypic definition rather than broadly applicable.
Complexity of Genetic Architecture and Environmental Influences
Section titled “Complexity of Genetic Architecture and Environmental Influences”Genetic studies of antimigraine preparation use often adjust for known demographic and lifestyle covariates, such as age, gender, smoking, and alcohol intake.[1]However, the complex interplay between genetic predispositions and unmeasured or unadjusted environmental factors, including diet, stress, or other comorbidities, can confound observed associations and limit the ability to isolate pure genetic effects. The existence of gene-environment interactions, where the effect of a genetic variant is modified by environmental exposure, may also lead to undetected associations if not specifically investigated.[7]Current genome-wide association studies typically focus on common single nucleotide polymorphisms (SNPs), which may not fully capture the complex genetic architecture underlying antimigraine preparation use.[7] It is plausible that multiple causal variants within the same gene, or rare variants not well-represented on genotyping arrays or imputation panels, contribute significantly to the trait but remain undiscovered.[5] This suggests that a substantial portion of the heritability for such complex traits remains unexplained, indicating a knowledge gap regarding the full spectrum of genetic influences beyond the identified common variants.[7]
Variants
Section titled “Variants”Genetic variations play a crucial role in influencing complex biological processes that underpin various health traits, including those potentially related to migraine susceptibility and the effectiveness of antimigraine preparations. Single nucleotide polymorphisms (SNPs) within or near genes involved in neuronal function, cellular regulation, and metabolic pathways can alter protein activity or expression, thereby modulating an individual’s physiological responses. Understanding these genetic underpinnings can offer insights into personalized approaches for managing conditions like migraine and assessing the impact of therapeutic interventions.[6] Variants near genes such as PHACTR1 and MEF2D are of particular interest due to their roles in neuronal and vascular function. _PHACTR1_ (Phosphatase and actin regulator 1) is involved in regulating the actin cytoskeleton, a critical component for cell shape, migration, and signaling within neurons and vascular cells. The variant rs9349379 in _PHACTR1_ might influence vascular tone or neuronal plasticity, factors that are highly relevant to the neurovascular hypothesis of migraine and the efficacy of treatments targeting these pathways. Similarly, _MEF2D_ (Myocyte Enhancer Factor 2D) is a transcription factor essential for neuronal development, synaptic plasticity, and survival, making variants like rs3790459 and rs10908504 potentially impactful on brain excitability and pain processing pathways, which could, in turn, affect the perception of migraine pain or the response to analgesics.[8] Such genetic differences contribute to the variability observed in how individuals experience migraine attacks and their reliance on antimigraine preparations.
Other genetic loci are implicated in fundamental cellular processes, including RNA regulation, protein modification, and cell differentiation, which can indirectly influence neurological health. The region encompassing _ZWINT_ (Zwillin and kinetochore protein) and _MIR3924_ (MicroRNA 3924) includes rs34747361 , which could affect cell division or microRNA-mediated gene regulation, potentially impacting neuronal repair or inflammatory responses. Similarly, variants rs34039083 and rs74809038 near the _RNU4-35P_ and _RNU4-76P_ genes, involved in RNA splicing, or rs4839828 and rs7770889 in _UFL1-AS1_, which may regulate protein ufmylation, could modify protein function or cellular stress responses that are relevant to chronic pain conditions. Moreover,_PRDM16_ (PR/SET Domain 16), a transcription factor involved in cell fate determination, carries variants like rs61759178 and rs61759167 that might affect neural stem cell differentiation or metabolic processes, thereby influencing overall physiological resilience or susceptibility to migraine.[9]These variations highlight how broad cellular mechanisms can contribute to individual differences in disease presentation and treatment outcomes.
Further genetic variations are found in genes governing membrane transport, receptor signaling, and extracellular matrix components. The _TRPM8_ (Transient Receptor Potential Cation Channel Subfamily M Member 8) gene, associated with rs4663983 (near _MSL3B_), encodes a cold and menthol-sensitive ion channel crucial for pain sensation and temperature perception, suggesting that variations here could alter pain thresholds relevant to migraine._LRP1_(Low-density lipoprotein receptor-related protein 1), with variantrs11172113 , is a multifaceted receptor involved in lipid metabolism, cell signaling, and the clearance of various ligands, including those involved in neuroinflammation and vascular health, which are often implicated in migraine pathophysiology. Additionally, _ASTN2_ (Astrotactin 2) plays a role in neuronal migration and synapse formation, and its variants rs7852872 and rs10759844 could impact brain structure and connectivity. Variants such as rs10849061 near _FGF23_(Fibroblast Growth Factor 23), a hormone regulating mineral metabolism, and_FGF6_ (Fibroblast Growth Factor 6), a growth factor involved in tissue repair, may influence systemic metabolic health or neurovascular integrity, thus potentially affecting migraine severity or an individual’s response to antimigraine strategies.[10] These diverse genetic influences collectively underscore the complex interplay of biological systems in migraine and its management.
Key Variants
Section titled “Key Variants”| RS ID | Gene | Related Traits |
|---|---|---|
| rs9349379 | PHACTR1 | coronary artery disease migraine without aura, susceptibility to, 4 migraine disorder myocardial infarction pulse pressure |
| rs34747361 | ZWINT - MIR3924 | antimigraine preparation use |
| rs4839828 rs7770889 | UFL1-AS1 | antimigraine preparation use |
| rs4663983 | MSL3B - TRPM8 | Anilide use antimigraine preparation use migraine disorder body height |
| rs11172113 | LRP1 | migraine disorder migraine without aura, susceptibility to, 4 FEV/FVC ratio, pulmonary function , smoking behavior trait FEV/FVC ratio, pulmonary function coronary artery disease |
| rs7852872 rs10759844 | ASTN2 | hippocampal volume antimigraine preparation use forced expiratory volume |
| rs61759178 rs61759167 | PRDM16 | antimigraine preparation use smoking initiation |
| rs34039083 rs74809038 | RNU4-35P - RNU4-76P | antimigraine preparation use |
| rs3790459 rs10908504 | MEF2D | antimigraine preparation use serum alanine aminotransferase amount |
| rs10849061 | FGF23 - FGF6 | migraine disorder antimigraine preparation use |
Defining Preparation Use
Section titled “Defining Preparation Use”Preparation use, in the context of health research, refers to the administration of specific therapeutic agents, primarily medications, for the management or treatment of various health conditions or symptoms. Operational definitions of preparation use involve the systematic identification of individuals who are actively undergoing specific medical treatments. For instance, studies explicitly define and track the use of “hypertension treatment (HTN Rx)” and “lipid therapy,” which is clarified as “drug treatment for hyperlipidemia”.[6], [11]Similarly, “hormone replacement therapy (HRT)” is recognized as a specific form of preparation use, particularly relevant in studies involving women.[6], [12], [13] The precise identification of individuals on such medications is crucial for accurately assessing baseline physiological traits and for understanding the true impact of biological factors independent of therapeutic interventions.
Categorization of Therapeutic Preparations
Section titled “Categorization of Therapeutic Preparations”Therapeutic preparations are classified primarily by the health condition they target or their pharmacological action. This allows for a structured approach to understanding the diverse landscape of medical treatments. Key categories identified in research include “anti-HTN therapy,” specifically for the management of hypertension, and “lipid therapy,” which addresses hyperlipidemia.[11]Another distinct category is “hormone replacement therapy,” which serves a different physiological purpose.[6], [12], [13] Such classifications enable researchers to group individuals based on their treatment status, facilitating comparisons and adjustments in analyses. This categorical approach helps in distinguishing between the inherent characteristics of a trait and those influenced by medical intervention, forming the basis for nuanced clinical and scientific interpretation.
Approaches to Quantifying and Adjusting for Preparation Use
Section titled “Approaches to Quantifying and Adjusting for Preparation Use”The evaluation of preparation use often involves recording the presence or absence of medication intake, and subsequently, adjusting for its influence on other measured traits. For example, when measuring blood pressure, the systolic blood pressure (SBP) of individuals on blood pressure medication is adjusted by adding 15 mm Hg, and their diastolic blood pressure (DBP) is adjusted by adding 10 mm Hg, to estimate values closer to an unmedicated state.[5]Beyond direct adjustments, preparation use is frequently incorporated as a covariate in statistical models to account for its confounding effects. This includes adjusting for “hypertension treatment use” and “lipid-lowering treatment use” in analyses of cardiovascular traits, or for “hormone therapy” in studies involving metabolic or other physiological measures.[11], [12], [13] Furthermore, specific criteria related to preparation use can lead to exclusions from analyses, such as excluding individuals with diabetes from lipid trait analyses, recognizing the potential impact of their condition and associated medications on measurements.[5]
Large-Scale Cohort Studies and Longitudinal Patterns
Section titled “Large-Scale Cohort Studies and Longitudinal Patterns”Large-scale cohort studies are fundamental to understanding the patterns of medication use within populations over time. Studies such as the ARIC Study, a prospective population-based cohort, have enrolled thousands of participants from diverse U.S. communities, enabling longitudinal follow-up for health outcomes and exposures.[14] These extensive cohorts are instrumental in understanding the temporal patterns of specific medication use, including antimigraine preparations, by repeatedly assessing health behaviors and prescription data over many years. Similarly, the Framingham Heart Study has provided a rich resource for investigating various health traits and their evolution over decades.[6] Biobank studies associated with these cohorts further allow for the integration of genetic information, which could potentially reveal associations between genetic loci and the propensity for using specific treatments, like antimigraine preparations, over an individual’s lifetime.
Cross-Population and Ancestry Comparisons
Section titled “Cross-Population and Ancestry Comparisons”Population studies frequently involve diverse cohorts, facilitating cross-population comparisons to identify variations in health traits and treatment responses across different ancestries and geographic regions.[2] For instance, large consortia encompassing 16 European population cohorts have been leveraged to examine genetic influences on lipid levels, demonstrating the power of such diverse datasets.[2]Applying this methodology to antimigraine preparation use could uncover population-specific effects, where the prevalence or efficacy of certain treatments might vary due to underlying genetic predispositions or environmental factors unique to different ethnic groups or geographic locations, as observed for metabolic traits in Japanese or Sardinian populations.[15] These comparisons are vital for understanding the global epidemiology of migraine treatment and for tailoring public health interventions.
Epidemiological Associations and Demographic Correlates
Section titled “Epidemiological Associations and Demographic Correlates”Epidemiological investigations are crucial for establishing the prevalence and incidence rates of specific conditions and their associated treatments, such as the use of antimigraine preparations, within defined populations. These studies often explore associations with various demographic factors, including age, gender, and socioeconomic status.[13]For example, analyses of large cohorts have adjusted for factors like age, gender, smoking, alcohol intake, body-mass index, and hormone-therapy use when studying metabolic traits.[1]Such detailed demographic and lifestyle data are essential for identifying subgroups with higher or lower rates of antimigraine preparation use and for understanding potential socioeconomic correlates that might influence access to or adherence with these treatments.
Methodological Considerations and Generalizability
Section titled “Methodological Considerations and Generalizability”The rigorous methodology employed in population studies includes various designs, such as genome-wide association studies (GWAS) and longitudinal cohort analyses, to ensure robust findings. Studies often involve thousands to tens of thousands of participants, like the cohorts contributing to lipid-level analyses or uric acid research.[2] Careful consideration is given to sample representativeness to ensure that findings can be generalized to broader populations, with imputation techniques and statistical adjustments for factors like age, gender, and geographical principal components being common practices.[1]However, variations in cohort characteristics, study designs, and genotyping platforms mean that generalizability to diverse populations requires careful interpretation, particularly when examining traits like antimigraine preparation use where population-specific factors may play a significant role.
Pharmacogenetics of Antimigraine Preparation Use
Section titled “Pharmacogenetics of Antimigraine Preparation Use”Pharmacogenetics explores how an individual’s genetic makeup influences their response to drugs. For antimigraine preparations, understanding these genetic variations can help explain differences in drug efficacy, adverse reactions, and optimal dosing among patients. By identifying specific genetic markers, it may be possible to personalize treatment strategies, leading to more effective and safer use of antimigraine therapies.
Genetic Variation Influencing Drug Metabolism and Pharmacokinetics
Section titled “Genetic Variation Influencing Drug Metabolism and Pharmacokinetics”Genetic variants in drug-metabolizing enzymes and transporters play a significant role in determining the pharmacokinetic profile of many medications. Cytochrome P450 (CYP) enzymes are a major family of enzymes responsible for metabolizing a wide range of drugs. Polymorphisms in genes encoding these enzymes can lead to distinct metabolic phenotypes, such as poor, intermediate, extensive, or ultrarapid metabolizers. These differences can result in varied drug concentrations in the body, which in turn affects therapeutic efficacy and the risk of adverse reactions. For example, pharmacogenomic studies have investigated variants in Glutathione S-transferase omega 1 and omega 2 enzymes, highlighting their role in drug processing.[16] Similarly, polymorphisms in genes like UGT1A1, which is involved in phase II metabolism, have been associated with altered levels of endogenous compounds such as bilirubin, indicating their general importance in drug detoxification and elimination.[17]Beyond CYP enzymes, genetic variations also affect drug transporters and other phase II enzymes, influencing drug absorption, distribution, and excretion. Collectively, these genetic differences determine the systemic exposure to a drug, shaping its pharmacokinetic profile. The comprehensive identification of genetic variants that influence the homeostasis of key metabolites, known as metabotypes, is essential for a deeper understanding of complex disease genetics and holds considerable promise for advancing individualized medication strategies.[18] Such insights could be crucial for predicting how quickly an antimigraine preparation is cleared from the body or how much reaches its target site.
Polymorphisms in Drug Targets and Pharmacodynamics
Section titled “Polymorphisms in Drug Targets and Pharmacodynamics”Genetic variations in drug targets can significantly influence how an individual responds to an antimigraine preparation at the pharmacodynamic level. Polymorphisms in genes encoding drug receptors, ion channels, or other target proteins can alter their structure, expression, or function, thereby affecting the drug’s binding affinity, signal transduction, or overall cellular response. For instance, common genetic variation near the MC4R (Melanocortin 4 Receptor) gene has been associated with metabolic traits, illustrating how receptor variants can influence physiological pathways.[19] Such alterations can lead to individuals experiencing different therapeutic effects or a varied susceptibility to specific adverse reactions from the same dose of an antimigraine preparation.
These genetic differences can manifest as a diminished therapeutic effect in some individuals, where the drug may not adequately alleviate migraine symptoms, or an exaggerated response, including severe side effects, in others, even if drug concentrations are within the expected range. Genome-wide association studies have extensively revealed numerous genetic loci influencing a wide array of human traits.[14] demonstrating the pervasive impact of genetic factors on biological processes, including those relevant to drug targets and their downstream signaling pathways. Understanding these target-specific genetic variations is vital for predicting the effectiveness and safety of antimigraine therapies.
Clinical Implementation for Personalized Antimigraine Prescribing
Section titled “Clinical Implementation for Personalized Antimigraine Prescribing”Integrating pharmacogenetic insights into clinical practice offers a pathway to optimize antimigraine treatment by personalizing drug selection and dosing strategies. Genetic testing could help identify individuals who are likely to experience altered drug metabolism or target response, enabling clinicians to make more informed decisions about prescribing specific antimigraine preparations. For example, understanding an individual’s metabolic phenotype through genetic variant analysis could guide initial dosing to achieve therapeutic concentrations more efficiently and safely, thereby avoiding sub-therapeutic levels that lead to treatment failure or toxic levels that cause severe adverse events.[18] This personalized approach has the potential to significantly improve therapeutic outcomes and reduce the incidence of adverse drug reactions associated with antimigraine preparations. While the development of comprehensive clinical guidelines for pharmacogenomics in migraine treatment is an evolving area, the continuous identification of genetic variants influencing various biological and metabolic traits.[18]strongly supports the future utility of pharmacogenomics in tailoring medication to an individual’s unique genetic makeup. Such advancements aim to move beyond a one-size-fits-all approach, leading to more effective and patient-specific migraine management.
Frequently Asked Questions About Antimigraine Preparation Use
Section titled “Frequently Asked Questions About Antimigraine Preparation Use”These questions address the most important and specific aspects of antimigraine preparation use based on current genetic research.
1. Why does my migraine medicine work great for me, but not my friend?
Section titled “1. Why does my migraine medicine work great for me, but not my friend?”It depends on your unique genetic makeup. Genetic variations influence how your body metabolizes antimigraine preparations and how effectively these drugs interact with their biological targets in your brain. This means that a drug perfectly suited for your genetic profile might not be as effective for your friend, or vice versa, due to differences in their genes affecting drug processing.
2. I get bad side effects from one migraine drug. Will another type be better for me?
Section titled “2. I get bad side effects from one migraine drug. Will another type be better for me?”Yes, it’s very possible. Your genetic profile significantly influences how drugs are absorbed, distributed, metabolized by enzymes (like liver enzymes), and excreted. If one drug causes side effects, another preparation with a different mechanism or metabolic pathway might be processed differently by your body, leading to fewer adverse effects and potentially better efficacy.
3. My sibling takes a different migraine medication. Will that one work for me too?
Section titled “3. My sibling takes a different migraine medication. Will that one work for me too?”Not necessarily. While you share many genes with your sibling, individual genetic variations can still lead to different responses to medications. Your specific genetic profile dictates how effectively a drug is processed and interacts with its targets, so what works best for your sibling might not be the optimal choice for you.
4. Does my family’s health history affect how well my migraine medicine works?
Section titled “4. Does my family’s health history affect how well my migraine medicine works?”Yes, family history can be a significant indicator. Shared genetic predispositions within your family can influence how you metabolize drugs and your body’s specific biological response to them. This genetic legacy can play a role in how effectively certain antimigraine preparations work for you.
5. I’m not of European descent. Does my background change how my migraine meds work?
Section titled “5. I’m not of European descent. Does my background change how my migraine meds work?”Yes, your ancestral background can be relevant. Many genetic studies on drug response have focused on populations of European descent, and genetic associations can differ across various ancestries. This means that drug responses identified in one population might not be directly applicable or as effective for individuals from different genetic backgrounds.
6. Could a DNA test really help me choose the best migraine medicine?
Section titled “6. Could a DNA test really help me choose the best migraine medicine?”Yes, it absolutely could. Understanding your genetic profile through a DNA test can provide insights into how your body metabolizes specific drugs (for example, through liver enzymes) and how efficiently they might interact with their biological targets. This information can guide healthcare providers in selecting a more personalized and effective antimigraine preparation for you.
7. Can taking too much migraine medicine actually make my headaches worse?
Section titled “7. Can taking too much migraine medicine actually make my headaches worse?”Yes, unfortunately, it can. Overuse or misuse of antimigraine preparations is a known risk factor for developing medication overuse headache, which can paradoxically increase the frequency and severity of your headaches. This highlights the importance of carefully monitoring your preparation use under medical guidance.
8. Does what I eat or my daily habits affect how well my migraine medicine works?
Section titled “8. Does what I eat or my daily habits affect how well my migraine medicine works?”Yes, environmental factors and lifestyle habits can influence drug efficacy. There’s a complex interplay between your genetic predispositions and factors like diet, smoking, or alcohol intake, which can affect how your body processes medication. These unmeasured or unadjusted environmental influences can impact how well your antimigraine preparation performs.
9. Why do some people need more of the same migraine medicine for the same pain?
Section titled “9. Why do some people need more of the same migraine medicine for the same pain?”This often comes down to individual genetic variations affecting drug metabolism. Some people may have genes that cause them to metabolize a drug more quickly, requiring a higher dose to achieve the same therapeutic effect. This difference in processing speed means the optimal dosage can vary significantly from person to person.
10. Will my children likely respond to migraine medicines like I do?
Section titled “10. Will my children likely respond to migraine medicines like I do?”They might, as genetic factors influencing drug response can be inherited from parents. However, each child also inherits a unique combination of genes, and their specific genetic profile, combined with their own environmental factors, will ultimately determine their individual response to antimigraine preparations.
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] Yuan, X, et al. “Population-based genome-wide association studies reveal six loci influencing plasma levels of liver enzymes.” Am J Hum Genet, vol. 83, no. 4, 2008, pp. 520-28. PMID: 18940312.
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[3] Willer, C. J. et al. “Newly identified loci that influence lipid concentrations and risk of coronary artery disease.”Nat Genet, vol. 40, no. 2, 2008, pp. 161-9.
[4] Kathiresan S, et al. “Common variants at 30 loci contribute to polygenic dyslipidemia.” Nat Genet, vol. 40, 2008, pp. 129-137.
[5] Sabatti, C, et al. “Genome-wide association analysis of metabolic traits in a birth cohort from a founder population.”Nat Genet, vol. 41, no. 1, 2009, pp. 35-46. PMID: 19060910.
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[7] Yang, Q., et al. “Genome-wide association and linkage analyses of hemostatic factors and hematological phenotypes in the Framingham Heart Study.”BMC Medical Genetics, vol. 8, 2007, p. 53.
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[9] Hwang SJ, et al. “A genome-wide association for kidney function and endocrine-related traits in the NHLBI’s Framingham Heart Study.” BMC Med Genet, vol. 8, 2007.
[10] Melzer D, et al. “A genome-wide association study identifies protein quantitative trait loci (pQTLs).” PLoS Genet, vol. 4, no. 5, 2008, e1000072.
[11] O’Donnell, C. J. et al. “Genome-wide association study for subclinical atherosclerosis in major arterial territories in the NHLBI’s Framingham Heart Study.”BMC Med Genet, vol. 8, 2007, p. 71.
[12] Vasan, R. S. et al. “Genome-wide association of echocardiographic dimensions, brachial artery endothelial function and treadmill exercise responses in the Framingham Heart Study.”BMC Med Genet, vol. 8, 2007, p. 70.
[13] Ridker, P. M. et al. “Loci related to metabolic-syndrome pathways including LEPR, HNF1A, IL6R, and GCKRassociate with plasma C-reactive protein: the Women’s Genome Health Study.”Am J Hum Genet, vol. 82, no. 5, 2008, pp. 1185-92.
[14] Dehghan, A, et al. “Association of three genetic loci with uric acid concentration and risk of gout: a genome-wide association study.”Lancet, vol. 372, no. 9654, 2008, pp. 1823-31. PMID: 18834626.
[15] Hiura, Y. et al. “Identification of genetic markers associated with high-density lipoprotein-cholesterol by genome-wide screening in a Japanese population: the Suita study.”Circ J, vol. 73, no. 4, 2009, pp. 745-9.
[16] Mukherjee, B, et al. “Glutathione S-transferase omega 1 and omega 2 pharmacogenomics.” Drug Metabolism and Disposition: The Biological Fate of Chemicals, vol. 34, no. 7, 2006, pp. 1237-1246.
[17] Lin, JP, et al. “Evidence for a gene influencing serum bilirubin on chromosome 2q telomere: a genomewide scan in the Framingham study.” Am J Hum Genet, vol. 72, 2003, pp. 1029-1034.
[18] Gieger, C, et al. “Genetics meets metabolomics: a genome-wide association study of metabolite profiles in human serum.”PLoS Genet, vol. 4, no. 11, 2008, e1000282. PMID: 19043545.
[19] Chambers, JC, et al. “Common genetic variation near MC4Ris associated with waist circumference and insulin resistance.”Nat Genet, vol. 40, no. 6, 2008, pp. 716-18. PMID: 18454146.