Metabolite Profiles
Introduction
Section titled “Introduction”The study of metabolite profiles, also known as metabolomics, is a rapidly evolving field that aims to comprehensively identify and quantify all endogenous metabolites within a biological system, such as a cell or body fluid.[1] These small molecules, including lipids, carbohydrates, and amino acids, represent the final downstream products of cellular regulatory processes.[1] By providing a functional readout of the physiological state of the human body.[1] metabolomics offers insights into dynamic biological processes.
Biological Basis
Section titled “Biological Basis”Metabolites are intrinsically linked to an individual’s genetic makeup, lifestyle, environment, and health status. They are the direct signatures of biochemical activity, reflecting the intricate interplay between an organism’s genes and its environment. Genetic variants can significantly influence the homeostasis of key metabolites, leading to alterations in their levels and contributing to phenotypic diversity and disease susceptibility.[1] Understanding these genetic associations with metabolite levels can reveal fundamental biological pathways and mechanisms.
Clinical Relevance
Section titled “Clinical Relevance”The analysis of metabolite profiles holds substantial clinical relevance. It enables the discovery of novel biomarkers for the early detection, diagnosis, prognosis, and monitoring of various diseases, including metabolic disorders, cardiovascular diseases, and cancers. By providing a snapshot of an individual’s metabolic state, this field facilitates a deeper understanding of disease pathogenesis and progression. Furthermore, metabolite profiling is crucial for pharmacometabolomics, which investigates how an individual’s metabolome influences their response to drugs, paving the way for personalized medicine.
Social Importance
Section titled “Social Importance”Beyond clinical applications, the study of metabolite profiles has broad social importance. It contributes to public health initiatives by identifying risk factors for common diseases and enabling population-level screening. By elucidating how diet, lifestyle, and environmental exposures impact human health at a molecular level, metabolomics can inform public health policies and personalized nutritional recommendations. Ultimately, advancements in metabolite profiling contribute to a more comprehensive understanding of human health and disease, fostering the development of precision health strategies tailored to individual needs.
Methodological and Identification Challenges
Section titled “Methodological and Identification Challenges”A significant limitation in metabolomics, particularly with untargeted approaches, is the difficulty in fully identifying all detected metabolite features. While spectral analysis can capture a comprehensive set of metabolic data, the complete chemical identification of every associated metabolite often requires extensive follow-up experimental work, such as two-dimensional NMR spectroscopy.[2] Such detailed analysis may be precluded by study protocols or sample destruction, meaning many detected features remain chemically unelucidated.[2] This lack of complete identification profoundly impacts the ability to derive direct mechanistic interpretations from genetic associations, even if unidentified metabolites can still serve as valuable biomarkers for clinical phenotypes.[2] Furthermore, variations in experimental conditions can pose challenges to the consistency and accuracy of metabolite measurements. Differences in experimental setups may cause significant changes in the chemical shifts of specific metabolite absorption bands.[2]Although some analytical approaches are designed to be robust against such variations, the potential for altered metabolite profiles due to non-standardized experimental conditions highlights a concern for the comparability and reliability of data across different experiments or cohorts. Improving the precision of metabolite concentration estimates, especially for signals of marginal strength, often necessitates further model-based quantification, which adds another layer of complexity to the analytical pipeline.[2]
Statistical Power and Replication Constraints
Section titled “Statistical Power and Replication Constraints”The detection of reliable genetic associations with metabolite levels is highly dependent on sufficient statistical power, which often demands very large sample sizes. Genetic associations, particularly with complex intermediate phenotypes like metabolites, frequently exhibit small effect sizes.[1] Consequently, studies with inadequate sample numbers risk missing true associations or reporting inflated effect sizes for detected variants, which can mislead subsequent research and interpretation.[1] The need to screen large populations, sometimes involving tens of thousands of participants, is crucial for achieving the necessary statistical power to identify novel genetic variants influencing metabolic traits.[1] Another critical limitation is the necessity for external replication of identified associations. Initial findings from discovery cohorts, especially in genome-wide association studies, require independent validation to confirm their robustness and generalizability.[3] Without such external replication, associations may represent false positives or be specific to the original study population, limiting their broader scientific utility. The absence of consistent replication across diverse cohorts impedes the translation of genetic insights into robust biological mechanisms or clinical applications, underscoring the importance of multi-cohort validation efforts.
Population Specificity and Confounding Context
Section titled “Population Specificity and Confounding Context”The generalizability of findings from metabolite studies can be significantly constrained by the demographic characteristics of the study populations. For instance, cohorts predominantly composed of individuals of specific ancestries, such as those of European descent, may yield results that are not directly applicable to more diverse populations.[3] This lack of ancestral diversity limits the ability to generalize observed gene-metabolite associations across different ethnic groups and highlights the potential for population-specific genetic architectures or environmental influences on metabolic traits. Future research must include more diverse populations to ensure the broad applicability and relevance of findings.[3]Furthermore, the interpretation of metabolite measurements and their genetic associations is inherently complex due to the pervasive influence of environmental and lifestyle factors, as well as gene-environment interactions. Metabolite levels are dynamic and reflect a continuous interplay between an individual’s genetic makeup and their external environment, including diet, physical activity, and exposures. Inadequate capture or control of these contextual factors can obscure true genetic effects, introduce confounding, or lead to misinterpretations of the observed associations. This complexity contributes to remaining knowledge gaps regarding the full etiology of metabolic variability and can underlie phenomena such as “missing heritability,” where the proportion of phenotypic variance explained by identified genetic variants is less than estimated heritability.
Variants
Section titled “Variants”Genetic variations play a crucial role in shaping an individual’s metabolic profile and susceptibility to various health conditions. Among these, variants within genes involved in N-acetylation, protein modification, and detoxification pathways are particularly significant. The NAT8 (N-acetyltransferase 8) gene, highly expressed in the kidneys, encodes an enzyme critical for N-acetylation, a process involved in detoxification and metabolism of various compounds. Variants such as rs13538 and rs4547554 , located in or near NAT8 and the pseudogene ALMS1P1, may influence the efficiency of this enzyme. Consequently, these genetic differences can affect the levels of N-acetylated metabolites, including N-acetylaspartate and N-acetylornithine, as well as creatinine, which are key indicators of kidney function and metabolic health.[4]Altered N-acetylation capacity, potentially due to these variants, has been linked to conditions such as chronic kidney disease and changes in glomerular filtration rate.[4] The ALMS1 gene, associated with Alström syndrome, is another important locus influencing metabolism. ALMS1plays roles in ciliary function, cell cycle regulation, and maintaining metabolic homeostasis, with mutations leading to a syndrome characterized by obesity, type 2 diabetes, and kidney dysfunction. Variants likers13391552 , rs6546861 , and rs13409366 within ALMS1 are thought to modulate these critical functions. These variations can impact the metabolism of N-acetylated compounds, reflecting ALMS1’s broader involvement in cellular processes that indirectly influence metabolite levels.[2] The interplay between ALMS1 and metabolic pathways underscores how genetic differences can affect a wide range of physiological traits, from detoxification to energy regulation.
The genomic region spanning ALMS1 and NAT8 also contains variants like rs10201159 and rs111540621 , suggesting a synergistic influence on shared metabolic pathways. Given that both ALMS1 and NAT8 are independently linked to N-acetylated compounds and kidney-related phenotypes, variants in this intergenic region may have pleiotropic effects on these interconnected processes.[4]These genetic variations contribute to the individuality of human metabolic profiles, influencing the efficiency of detoxification, amino acid processing, and overall kidney health. Understanding the impact of these variants on metabolite measurements provides insights into the genetic underpinnings of complex metabolic traits and disease risk.
Key Variants
Section titled “Key Variants”| RS ID | Gene | Related Traits |
|---|---|---|
| rs45446698 | CYP3A7 - CYP3A4 | heel bone mineral density body height estradiol C-reactive protein gout |
| rs13538 rs4547554 | NAT8, ALMS1P1, ALMS1P1 | chronic kidney disease, serum creatinine amount hydroxy-leucine serum metabolite level serum creatinine amount, glomerular filtration rate urinary metabolite |
| rs2066938 rs7313271 rs12829722 | UNC119B | metabolite serum metabolite level protein butyrylcarnitine ethylmalonate |
| rs174528 rs174533 | MYRF, TMEM258 | phosphatidylcholine ether serum metabolite level vaccenic acid gondoic acid kit ligand amount |
| rs1047891 rs715 rs6760497 | CPS1 | platelet count erythrocyte volume homocysteine chronic kidney disease, serum creatinine amount circulating fibrinogen levels |
| rs13391552 rs6546861 rs13409366 | ALMS1 | metabolite serum metabolite level |
| rs1943379 | NAALAD2 | beta-citrylglutamate metabolite serum metabolite level |
| rs10201159 rs111540621 | ALMS1 - NAT8 | 2-aminooctanoate metabolite N-acetyl-3-methylhistidine N-acetylglutamine N-acetylarginine |
| rs5751777 | MIF-AS1 - KLHL5P1 | alkaline phosphatase blood protein amount metabolite 3-formylindole 3-indoleglyoxylic acid |
| rs36209093 | GSTM2 | free cholesterol:totallipids ratio, high density lipoprotein cholesterol cholesteryl ester , high density lipoprotein cholesterol lipid , high density lipoprotein cholesterol phospholipid amount, high density lipoprotein cholesterol 3,7-dimethylurate |
Defining Metabolites and Metabolomics
Section titled “Defining Metabolites and Metabolomics”Metabolites are small molecules that are products or intermediates of metabolism, encompassing a vast array of endogenous biochemicals within an organism. The study of these intricate ‘metabolite profiles’ in biological samples, such as human serum, forms the conceptual framework of metabolomics. This field aims for the comprehensive identification and quantification of all metabolites present, offering a snapshot of an organism’s physiological state. The precise definition of a metabolite can include diverse molecules like free prostaglandins and lipoxygenase-derived fatty acid metabolites, which are crucial for various biological functions.[1] Metabolomics, as a key term, represents a powerful approach to understanding biological systems and their responses to genetic, environmental, or pathological changes.
Operational Definitions and Approaches
Section titled “Operational Definitions and Approaches”The operational definition of metabolite profiling involves specific approaches designed for comprehensive and quantitative analysis. Techniques such as Liquid Chromatography-Mass Spectrometry/Mass Spectrometry (LC-MS/MS) are central to this process, enabling the simultaneous quantitation of numerous metabolites. These methods often require rapid sample preparation and can operate effectively with small sample volumes, ensuring both efficiency and the preservation of sample integrity.[1]The rigorous application of these criteria allows for the generation of reliable ‘metabolite profiles’ that can be consistently compared across different studies and populations.
Clinical and Research Classification
Section titled “Clinical and Research Classification”Metabolite measurements play a significant role in developing classification systems for various conditions, particularly in diagnosing metabolic diseases.[5]The identification of specific ‘biomarkers’ – measurable indicators of a biological state or condition – is a primary application, contributing to both clinical and research criteria for disease diagnosis and characterization.[6]By analyzing metabolite profiles, researchers can identify distinct patterns that may correlate with disease subtypes, severity gradations, or responses to treatment, thereby refining nosological systems. This approach moves beyond categorical diagnoses to potentially more dimensional understandings of health and disease states based on molecular signatures.
The Central Role of Metabolites in Cellular Metabolism and Homeostasis
Section titled “The Central Role of Metabolites in Cellular Metabolism and Homeostasis”Metabolomics aims at a comprehensive profiling of endogenous metabolites in biological samples, providing a functional readout of the physiological state of the human body. These diverse chemical compounds are the direct products and intermediates of countless cellular metabolic processes, playing fundamental roles in energy production, biosynthesis, and the detoxification of waste products. The intricate balance and concentration of these molecules are essential for maintaining cellular functions and overall physiological homeostasis, with disruptions serving as potential indicators of underlying biological imbalances. Key biomolecules, particularly enzymes, are central to these metabolic pathways, catalyzing the biochemical reactions that govern metabolite transformations. The specific activity and substrate affinity of these enzymes dictate the flux through various metabolic routes, directly influencing the concentration levels of specific metabolites. Beyond enzymes, a variety of transport proteins are also critical for the disposition and distribution of metabolites within and between cells, as well as across different tissues and organs, ensuring their proper utilization and clearance.[1]
Genetic Architecture of Metabolite Regulation
Section titled “Genetic Architecture of Metabolite Regulation”Genetic mechanisms exert a profound influence on circulating metabolite levels, with specific genetic variants acting as key determinants of an individual’s metabolome. These genetic variations can alter gene functions through several pathways, such as modifying the expression levels of messenger RNAs or affecting the properties of the respective enzymes or transport proteins via changes in their amino acid sequences. Such alterations can impact enzyme activity, substrate specificity, or the efficiency of metabolite transport, thereby directly influencing metabolite concentrations.
Systemic Interplay and Organ-Specific Contributions
Section titled “Systemic Interplay and Organ-Specific Contributions”Metabolite profiles observed in biofluids, such as human serum, represent a systemic snapshot that reflects the intricate interplay of metabolic activities across various tissues and organs throughout the body. Each organ contributes uniquely to the overall metabolic landscape, performing specialized functions that collectively maintain systemic metabolic balance. For example, the liver plays a critical role in nutrient metabolism and detoxification, while the kidneys are essential for filtering waste metabolites and regulating electrolyte balance. These organ-specific metabolic contributions are integrated and coordinated through complex systemic regulatory networks, which involve hormones, signaling pathways, and inter-organ communication. Disruptions in the function of one organ can therefore cascade into systemic consequences, leading to altered levels of numerous circulating metabolites and potentially impacting the homeostatic balance of the entire organism. Such systemic consequences highlight the interconnectedness of biological systems and the importance of a holistic view in understanding metabolite levels.
Metabolites as Indicators of Health and Pathophysiology
Section titled “Metabolites as Indicators of Health and Pathophysiology”Metabolites are hypothesized to play key roles as both markers and effectors in various pathophysiological processes, including complex conditions like cardiometabolic diseases. Deviations from normal metabolite homeostasis can serve as critical signals for the onset or progression of disease, providing a dynamic and functional readout of the body’s physiological state. For instance, altered levels of key lipids, carbohydrates, or amino acids are frequently associated with metabolic dysregulation and disease risk.[3]The comprehensive analysis of metabolite profiles can reveal underlying disease mechanisms, offering valuable insights into homeostatic disruptions and the body’s compensatory responses to pathological states or environmental stressors. By integrating genomic information with metabolomic data, research efforts aim to refine and expand the understanding of how genetic predispositions interact with metabolic alterations to contribute to disease development, ultimately paving the way for improved diagnostic strategies and targeted therapeutic interventions.[3]
Core Metabolic Pathways and Their Regulation
Section titled “Core Metabolic Pathways and Their Regulation”The intricate balance of metabolite levels within the human body is fundamentally governed by core metabolic pathways, encompassing processes such as energy metabolism, biosynthesis, and catabolism. Genetic variation plays a significant role in shaping an individual’s metabolic individuality, with specific loci identified that influence the disposition of various metabolites in biological fluids like urine.[4] These genetic variants often affect enzymes or transport proteins directly involved in the synthesis, breakdown, or transport of metabolites, exerting relatively large effect sizes on their circulating levels compared to typical genome-wide association study findings for common diseases.[3] The homeostasis of key lipids, carbohydrates, and amino acids is particularly sensitive to these genetic influences, providing a functional readout of the physiological state.[1] Metabolic regulation and flux control within these pathways are achieved through mechanisms like allosteric control, where metabolite binding to an enzyme at a site other than the active site can modulate its activity, ensuring efficient resource allocation and adaptation to changing cellular demands.
Signal Transduction and Transcriptional Control of Metabolism
Section titled “Signal Transduction and Transcriptional Control of Metabolism”Metabolite levels are also tightly regulated by complex signaling pathways that orchestrate gene expression and protein activity. While specific details of receptor activation and intracellular signaling cascades are broad, the overall regulation of gene expression is a critical determinant of metabolic phenotypes. Genetic variations can lead to alterations in gene expression, which in turn impact the production of metabolic enzymes or transporters, thereby influencing metabolite concentrations.[7] Transcription factor regulation, often activated or repressed by upstream signaling cascades, dictates the synthesis rates of proteins involved in metabolic pathways. These regulatory mechanisms can also include post-translational modifications of metabolic enzymes, such as phosphorylation or acetylation, which rapidly alter protein function and enzyme kinetics, providing dynamic control over metabolic flux and offering feedback loops to maintain metabolic equilibrium.
Interconnectedness and Systems-Level Homeostasis
Section titled “Interconnectedness and Systems-Level Homeostasis”The human metabolome is not a collection of isolated pathways but rather a highly interconnected network exhibiting systems-level integration. Metabolomics research, often combined with genomic data, leverages this interconnectedness to understand the causal determinants of circulating metabolite levels.[3] Pathway crosstalk and network interactions are pervasive, where metabolites from one pathway can influence enzymes or signaling molecules in another, creating a complex web of regulation. A systems approach, utilizing methods like Gaussian graphical modeling, can reconstruct pathway reactions from high-throughput metabolomics data, revealing functional interaction networks of proteins that are globally integrated and scored.[7] These emergent properties of the metabolic network, arising from the hierarchical regulation of genes, proteins, and metabolites, collectively define the overall physiological state and metabolic individuality of an organism.
Metabolic Dysregulation in Disease
Section titled “Metabolic Dysregulation in Disease”Dysregulation within these intricate metabolic and signaling pathways is a hallmark of numerous diseases, with metabolites serving as crucial markers and effectors, particularly in cardiometabolic diseases.[3]Genetic variants that lead to changes in the homeostasis of key metabolites like lipids, carbohydrates, or amino acids can predispose individuals to disease states.[1] When pathways become dysregulated, compensatory mechanisms may be activated to restore balance, but persistent imbalances can lead to pathological conditions. Understanding the specific molecular interactions and pathway components involved in metabolic individuality and dysregulation is critical for identifying potential therapeutic targets. For instance, identifying loci associated with specific metabolite disposition can pinpoint enzymes or transporters whose modulation could offer avenues for therapeutic intervention in metabolic disorders.[3]
Diagnostic and Prognostic Utility
Section titled “Diagnostic and Prognostic Utility”Metabolite measurements offer a functional readout of the body’s physiological state, providing valuable insights into disease presence and progression.[1]The comprehensive of endogenous metabolites in bodily fluids can serve as a powerful diagnostic tool, reflecting metabolic alterations characteristic of various conditions. Beyond diagnosis, these measurements hold significant prognostic value, capable of predicting disease outcomes, the trajectory of disease progression, and long-term health implications. For instance, in cardiometabolic diseases, specific metabolite profiles are hypothesized to act as key markers and effectors, allowing for early identification of at-risk individuals and anticipating future clinical events.[3] The integration of genomic and metabolomic data further refines our understanding of the causal determinants of circulating metabolite levels, leading to more precise prognostic indicators.[3]
Risk Stratification and Personalized Medicine
Section titled “Risk Stratification and Personalized Medicine”Metabolite levels are instrumental in risk assessment, enabling clinicians to identify individuals at high risk for developing complex diseases, particularly cardiometabolic conditions.[3] By providing a detailed snapshot of an individual’s metabolic state, these measurements facilitate advanced risk stratification beyond traditional clinical parameters. This granular insight supports personalized medicine approaches, where prevention strategies and treatment selections can be tailored to an individual’s unique metabolic profile. Understanding how genetic variants influence the homeostasis of key lipids, carbohydrates, or amino acids via metabolomic profiles allows for the development of highly specific interventions.[1]Such personalized strategies can optimize treatment efficacy and minimize adverse effects, moving towards more targeted patient care and effective disease monitoring.
Elucidating Disease Mechanisms and Comorbidities
Section titled “Elucidating Disease Mechanisms and Comorbidities”The comprehensive analysis of metabolites provides a functional readout of the physiological state, offering a deeper understanding of the underlying mechanisms of disease.[1]By identifying specific metabolic perturbations, researchers can pinpoint key pathways involved in disease pathophysiology, which can lead to novel therapeutic targets. Metabolite measurements are also crucial for recognizing related conditions, complications, and overlapping phenotypes, particularly in complex syndromic presentations. For cardiometabolic diseases, integrating genomic and metabolomic data helps clarify the causal determinants of circulating metabolite levels, shedding light on the intricate connections between various health conditions.[3] This improved understanding allows for better management of comorbidities and a more holistic approach to patient care, addressing the multifaceted nature of chronic diseases.
Frequently Asked Questions About Metabolite
Section titled “Frequently Asked Questions About Metabolite”These questions address the most important and specific aspects of metabolite based on current genetic research.
1. Why do some foods make me feel sluggish but my friend is fine?
Section titled “1. Why do some foods make me feel sluggish but my friend is fine?”Your genetic makeup influences how your body processes different foods, leading to unique metabolite profiles. Variations in certain genes can alter how you metabolize carbohydrates or fats, directly affecting your energy levels and how you feel after eating. This is why personalized nutritional recommendations are so important for optimizing your health.
2. Can my daily stress actually change how my body works inside?
Section titled “2. Can my daily stress actually change how my body works inside?”Yes, absolutely. Stress is a significant environmental factor that interacts with your genes to influence metabolite levels. This dynamic interplay can alter your body’s biochemical activity, affecting everything from energy metabolism to inflammation, which can contribute to various health issues over time.
3. My family has a history of diabetes – can I prevent it with my diet?
Section titled “3. My family has a history of diabetes – can I prevent it with my diet?”While you might have a genetic predisposition due to family history, your diet and lifestyle play a huge role. Understanding how your specific genetic variants influence key metabolite levels can help tailor nutritional strategies to mitigate risk and promote health, making prevention more effective foryou.
4. Is it true that my ethnicity affects my health risks differently?
Section titled “4. Is it true that my ethnicity affects my health risks differently?”Yes, it can. Research shows that genetic architectures and environmental influences on metabolic traits can vary significantly across different ethnic groups. This means findings from one population might not apply directly to another, underscoring the importance of diverse research to understand your specific risks.
5. I exercise regularly, but still struggle with my weight. Why?
Section titled “5. I exercise regularly, but still struggle with my weight. Why?”Your genetic makeup can significantly influence your metabolism and how your body responds to exercise. Genetic variants can alter the homeostasis of key metabolites involved in energy balance, meaning that even with consistent effort, some individuals may face greater challenges due to their unique biological predispositions.
6. If I get a health test, will it tell me everything about my metabolism?
Section titled “6. If I get a health test, will it tell me everything about my metabolism?”While advanced tests can identify many metabolites, fully identifying every single molecule in your system is still a major challenge in science. Many detected features might remain chemically unelucidated, meaning the full picture of every metabolic pathway isn’t always completely clear, though valuable insights are still gained.
7. Why did that new diet work for my coworker but not for me?
Section titled “7. Why did that new diet work for my coworker but not for me?”Everyone’s body processes food differently due to their unique genetic makeup and individual metabolome. What works well for one person might not be optimal for another because their metabolic responses to specific diets can vary significantly. This highlights why personalized nutritional recommendations, considering your unique biology, are much more effective than one-size-fits-all diets.
8. Does lack of sleep really mess up my body’s chemistry?
Section titled “8. Does lack of sleep really mess up my body’s chemistry?”Absolutely. Sleep is a crucial lifestyle factor that deeply interacts with your genetic predispositions, influencing your body’s metabolite levels. Inadequate sleep can disrupt the delicate balance of these small molecules, potentially affecting metabolic processes, hormone regulation, and overall health.
9. My doctor prescribed a drug, but it didn’t work well. Is it me?
Section titled “9. My doctor prescribed a drug, but it didn’t work well. Is it me?”It’s not necessarily “you” in a negative sense, but your unique metabolome can influence how your body processes and responds to medications. This field, called pharmacometabolomics, studies how an individual’s specific metabolic profile affects drug efficacy and side effects, paving the way for more personalized treatment.
10. Could a blood test really predict my risk for certain diseases years away?
Section titled “10. Could a blood test really predict my risk for certain diseases years away?”Potentially, yes. Metabolite profiles can reveal novel biomarkers that offer insights into your current physiological state and future disease risk. By providing a snapshot of your metabolic health, these tests can contribute to early detection, diagnosis, and even prognosis for various conditions long before symptoms appear.
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] 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.
[2] Rueedi, Remo, et al. “Genome-Wide Association Study of Metabolic Traits Reveals Novel Gene-Metabolite-Disease Links.”PLoS Genetics, vol. 10, no. 2, 2014, p. e1004132.
[3] Rhee, E. P., et al. “A Genome-Wide Association Study of the Human Metabolome in a Community-Based Cohort.” Cell Metabolism, vol. 18, no. 1, 2013, pp. 130-43.
[4] Raffler, Johannes, et al. “Genome-Wide Association Study with Targeted and Non-Targeted NMR Metabolomics Identifies 15 Novel Loci of Urinary Human Metabolic Individuality.” PLoS Genetics, vol. 11, no. 9, 2015, p. e1005486.
[5] Weinberger, K. M. “Metabolomics in diagnosing metabolic diseases.” Ther Umsch, 2008.
[6] Weinberger, K. M., and A. Graber. “Using Comprehensive Metabolomics to Identify Novel Biomarkers.” Screening Trends in Drug Discovery, 2005.
[7] Krumsiek, Jan, et al. “Mining the Unknown: A Systems Approach to Metabolite Identification Combining Genetic and Metabolic Information.” PLoS Genetics, vol. 8, no. 10, 2012, e1003009.