Executive Function
Executive function is a comprehensive term referring to a set of higher-order cognitive processes that govern and regulate an individual’s thoughts and actions. These essential mental skills are crucial for goal-directed behavior, problem-solving, and successful adaptation to novel or complex situations. Core components of executive function typically include working memory (the ability to hold and manipulate information), inhibitory control (the capacity to suppress impulses and irrelevant information), and cognitive flexibility (the skill to switch between tasks or mental sets).
Biological Basis
Section titled “Biological Basis”The biological underpinnings of executive function are primarily rooted in the prefrontal cortex of the brain, a region that undergoes prolonged development from childhood through early adulthood. This area orchestrates complex neural networks, integrating information from various brain regions to facilitate decision-making and behavioral regulation. Neurotransmitter systems, particularly those involving dopamine and serotonin, play significant roles in modulating these functions. Genetic factors are understood to contribute to individual variations in executive function by influencing brain development, neural connectivity, and the efficiency of these neurotransmitter systems.
Clinical Relevance
Section titled “Clinical Relevance”Deficits in executive function are associated with a wide range of neurological and psychiatric conditions. These include neurodevelopmental disorders such as Attention-Deficit/Hyperactivity Disorder (ADHD) and autism spectrum disorder, as well as mental health conditions like schizophrenia and depression. Neurodegenerative diseases, such as Parkinson’s disease and Alzheimer’s disease, also commonly present with executive dysfunction. Furthermore, brain injuries, strokes, and substance abuse can impair these critical cognitive abilities. The assessment of executive function is therefore vital for accurate diagnosis, predicting outcomes, and guiding therapeutic interventions in clinical settings.
Social Importance
Section titled “Social Importance”Beyond clinical contexts, robust executive functions are fundamental for navigating daily life and achieving personal and professional success. They enable individuals to plan effectively, prioritize tasks, manage time efficiently, resist distractions, and regulate emotional responses. These skills are critical for academic achievement, career advancement, financial management, and fostering healthy social relationships. Conversely, impairments can lead to significant challenges in learning, employment stability, independent living, and overall quality of life, highlighting their profound impact on an individual’s capacity to function effectively within society.
Methodological and Statistical Challenges
Section titled “Methodological and Statistical Challenges”Genetic investigations into complex traits like executive function often encounter significant statistical and methodological hurdles. A common issue is the limited statistical power in studies with moderate sample sizes, which frequently prevents the detection of genetic variants with modest effect sizes, especially when accounting for the extensive multiple testing inherent in genome-wide association studies (GWAS).[1] Consequently, many observed associations may not reach genome-wide significance, leading to findings that are considered hypothesis-generating and require further replication.[1] This situation can also contribute to an inflation of reported effect sizes in initial discovery cohorts, which may diminish upon replication.[1] The challenge of replication is further compounded by potential false positive associations, differences in study design, or varying statistical power across cohorts, which can lead to non-replication at the specific SNP level even if underlying causal variants are shared.[2]Furthermore, genotyping platforms used in early GWAS, such as the Affymetrix 100K GeneChip, provided only partial coverage of the human genome, potentially missing important genetic variations or entire genes that influence executive function.[1] Discrepancies can also arise from the use of different analytical methods within a single study, which may yield non-overlapping top associations, complicating the interpretation and prioritization of findings.[1]These statistical and design constraints necessitate cautious interpretation of initial findings and highlight the critical need for large, well-powered, and diverse replication cohorts to validate genetic associations with executive function.
Phenotypic Definition and Measurement Variability
Section titled “Phenotypic Definition and Measurement Variability”Defining and consistently measuring complex phenotypes like executive function presents substantial challenges that can limit the generalizability and interpretability of genetic findings. Longitudinal studies, while valuable for capturing trait evolution, may introduce misclassification if measurements are averaged across long periods or if different equipment is used over time, potentially masking age-dependent genetic effects.[1] Moreover, the assumption that the same genetic and environmental factors influence traits over a wide age range may not hold true, suggesting that age-specific genetic effects could be overlooked when observations are averaged.[1] Another concern is the potential for ascertainment or survival bias, particularly in cohorts where DNA collection occurs at later examinations, meaning the study population might not fully represent the broader population.[2] Additionally, sex-specific genetic associations might remain undetected if analyses are only performed in sex-pooled cohorts to mitigate multiple testing issues.[3]These phenotypic complexities underscore the necessity for precise, standardized phenotyping across studies and careful consideration of demographic and temporal factors to improve the accuracy and relevance of genetic discoveries for executive function.
Population Diversity and Environmental Context
Section titled “Population Diversity and Environmental Context”Genetic insights into executive function are often constrained by the demographic homogeneity of study populations and the intricate interplay between genes and environment. Many foundational genetic studies, for instance, have predominantly included individuals of white European ancestry, raising questions about the generalizability of findings to other ethnic or racial groups.[2] While efforts are made to control for population stratification through methods like principal component analysis, residual ancestral differences within seemingly homogeneous groups can still confound genetic associations.[4] Beyond population structure, genetic variants can exert their influence in a context-specific manner, with environmental factors significantly modulating their effects.[1]For instance, gene-environment interactions, such as diet influencing the effect of specific genes on physiological traits, are rarely comprehensively investigated in genetic studies, leaving a substantial gap in understanding the full etiology of complex traits like executive function.[1] Despite observed heritability for many complex traits, the specific genetic variants identified through GWAS often explain only a fraction of this heritability, pointing to the phenomenon of “missing heritability” which may be attributed to unmeasured environmental factors, rare variants, or complex gene-gene interactions not fully captured by current approaches. Addressing these limitations requires more diverse cohorts and studies designed to explicitly explore gene-environment interactions.
Variants
Section titled “Variants”The genetic landscape influencing executive function involves a range of genes and variants, each contributing to fundamental biological processes within the brain. These include genes involved in lipid metabolism, synaptic communication, cell adhesion, and gene regulation, all of which are crucial for optimal cognitive performance. Understanding these variants can shed light on the molecular underpinnings of cognitive abilities, including planning, working memory, and decision-making.
The _APOE_ gene plays a significant role in lipid metabolism, particularly in the transport and processing of fats and cholesterol within the brain and body. The rs429358 variant, in conjunction with rs7412 , defines the common _APOE_ alleles (e2, e3, e4), which have substantial health implications. The _APOE_ gene cluster, which also includes _APOC1_, _APOC4_, and _APOC2_, has been consistently linked to variations in low-density lipoprotein (LDL) cholesterol concentrations..[5]Specific alleles are associated with altered LDL cholesterol levels, a known risk factor for cardiovascular disease..[6]Regarding executive function, the_APOE_ e4 allele, partly defined by the rs429358 variant, is a well-established genetic risk factor for Alzheimer’s disease and is associated with accelerated cognitive decline, affecting executive functions such as planning, problem-solving, and working memory.
Genes like _EXOC4_ and _TSNARE1_ are central to synaptic function, which is critical for brain communication. _EXOC4_ encodes a component of the exocyst complex, essential for regulated exocytosis, the process by which cells release molecules like neurotransmitters to communicate. Variants such as rs12707117 , rs2160746 , rs2430768 , rs763646 , and rs10246665 in _EXOC4_ could influence the efficiency of this cellular machinery, impacting neurotransmitter release. Similarly, _TSNARE1_ (Trafficking SNARE 1) is involved in vesicle trafficking and membrane fusion, vital for the precise release of neurotransmitters at synapses. The rs13262595 variant in _TSNARE1_ might alter synaptic strength and communication, thereby affecting neural circuits that support executive functions. Both _EXOC4_ and _TSNARE1_are fundamental to synaptic plasticity and efficient neuronal signaling, and variations in these genes can affect higher-order cognitive abilities like working memory, attention, and cognitive flexibility, all crucial components of executive function..[7] Genome-wide association studies have identified various loci contributing to complex traits, indicating that genes involved in fundamental cellular processes can have widespread effects on overall health and cognition..[5] Other variants affect genes involved in cell adhesion and neuronal development. The rs147711004 variant is located in a region encompassing _BCAM_ (Basal Cell Adhesion Molecule) and _NECTIN2_ (Nectin Cell Adhesion Molecule 2), both essential for cell-cell adhesion. These adhesion molecules play vital roles in the precise formation and maintenance of neural networks during brain development and throughout life..[8] Proper neuronal connectivity is indispensable for the efficient processing of information that underlies executive functions. Likewise, _NEDD9_ (Neural Precursor Cell Expressed, Developmentally Down-regulated 9) is involved in cell adhesion, migration, and signaling pathways crucial for neuronal development and plasticity. The rs36120363 and rs6904209 variants in this region, which also includes _RNU1-64P_ (a small nuclear RNA pseudogene), could impact these processes, potentially affecting the structural and functional integrity of brain regions vital for executive control. Alterations in these genes may subtly influence cognitive processing speed, decision-making, and behavioral regulation..[9] Long intergenic non-coding RNAs (lincRNAs), such as those encoded by _LINC01414_ and _LINC01122_, play important regulatory roles in gene expression, influencing various biological processes, including brain development and function. Variants like rs812603 in _LINC01414_ and rs7582485 , rs1990641 in _LINC01122_ could alter the expression or function of these regulatory RNAs, potentially impacting neuronal differentiation and synaptic function..[2] Similarly, the region containing _SFMBT1_ (Scm-like with Four MBT Domains 1) and _SERBP1P3_ (a pseudogene) involves variants such as rs2581789 and rs11915851 . _SFMBT1_ is a chromatin-binding protein involved in the epigenetic regulation of gene expression, a mechanism critical for long-term neuronal plasticity and memory formation..[10] The rs148528269 variant in the _RPL7AP50_ - _DBF4P1_region (both pseudogenes) might also contribute to altered gene regulation. Collectively, variations in these non-coding and regulatory elements can subtly modulate the complex gene expression patterns within the brain, thereby influencing the neural underpinnings of executive function, including cognitive control and adaptive behavior.
Key Variants
Section titled “Key Variants”| RS ID | Gene | Related Traits |
|---|---|---|
| rs429358 | APOE | cerebral amyloid deposition measurement Lewy body dementia, Lewy body dementia measurement high density lipoprotein cholesterol measurement platelet count neuroimaging measurement |
| rs12707117 rs2160746 | EXOC4 | executive function measurement |
| rs147711004 | BCAM - NECTIN2 | anxiety measurement, triglyceride measurement Alzheimer disease Alzheimer’s disease biomarker measurement C-reactive protein measurement body mass index |
| rs812603 | LINC01414 | executive function measurement |
| rs2581789 rs11915851 | SFMBT1 - SERBP1P3 | cognitive domain measurement executive function measurement |
| rs148528269 | RPL7AP50 - DBF4P1 | executive function measurement information processing speed, cognitive function measurement, major depressive disorder cognitive function measurement, major depressive disorder |
| rs2430768 rs763646 rs10246665 | EXOC4 | executive function measurement |
| rs36120363 rs6904209 | NEDD9 - RNU1-64P | executive function measurement information processing speed, cognitive function measurement |
| rs7582485 rs1990641 | LINC01122 | episodic memory mathematical ability executive function measurement |
| rs13262595 | TSNARE1 | intelligence health study participation executive function measurement cognitive function measurement anxiety measurement |
Conceptualization and Related Cognitive Traits
Section titled “Conceptualization and Related Cognitive Traits”Research explores various facets of cognitive functioning, with “cognitive performance” emerging as an observable and quantifiable characteristic. While the provided studies do not explicitly detail a precise, overarching definition for ‘executive function’, they do present “cognitive performance” as a measurable aspect of an individual’s cognitive abilities.[11] This trait is considered within broader health studies, aiming to understand its connections to biological markers and overall well-being. The investigation of such cognitive traits contributes to a comprehensive view of human health and the factors influencing mental processes.
Operational Definitions and Measurement Approaches
Section titled “Operational Definitions and Measurement Approaches”For research purposes, “cognitive performance” has been operationally defined and measured through a standardized approach. Specifically, studies have assessed this trait “based on a global score averaging 6 cognitive tests”.[11] This method provides a quantitative means of evaluating an individual’s cognitive functioning, allowing for consistent data collection and analysis across study participants. Such standardized measurement is crucial for establishing reliable associations between cognitive traits and various physiological or environmental factors.
Clinical Associations
Section titled “Clinical Associations”Clinical investigations have highlighted significant associations between “cognitive performance” and specific nutritional factors. Studies have observed that women in the “lowest quartile of plasma vitamin B12 levels had marginally worse cognitive performance”.[11]Furthermore, research indicates that a “combined folate and vitamin B12 deficiency was associated with the lowest cognitive performance”.[11] These findings underscore the clinical importance of cognitive performance as an indicator of health and its potential vulnerability to certain nutritional deficiencies, suggesting avenues for intervention and further study.
Biological Background
Section titled “Biological Background”The biological underpinnings of complex traits, often referred to as aspects of “executive function” in a broad biological sense, involve intricate molecular, cellular, and systemic processes. These processes are regulated by genetic mechanisms, influenced by key biomolecules, and manifest at the tissue and organ levels, contributing to overall physiological health and disease susceptibility. Understanding these biological pathways provides insight into the regulation of various metabolic and cardiovascular traits.
Genetic Regulation of Metabolic Pathways
Section titled “Genetic Regulation of Metabolic Pathways”Genetic mechanisms play a crucial role in shaping an individual’s metabolic profile and influencing health outcomes. Specific genes and their regulatory elements dictate the production and function of proteins essential for metabolic processes. For instance, a null mutation in the human gene APOC3 has been observed to lead to a favorable plasma lipid profile and apparent cardioprotection, highlighting its significant role in lipid metabolism.[12] Similarly, ANGPTL3 is known to regulate lipid metabolism, while variations in ANGPTL4can reduce triglyceride levels and increase high-density lipoprotein (HDL).[6]Furthermore, common single nucleotide polymorphisms (SNPs) in theHMGCRgene are associated with low-density lipoprotein cholesterol (LDL-C) levels, impacting alternative splicing of exon 13, which can alter protein function.[13] Other genes, such as GALNT2, which encodes an enzyme involved in O-linked glycosylation, can regulate many proteins, potentially influencing HDL cholesterol and triglyceride metabolism.[5] The transcription factor MLXIPLalso plays a role in triglyceride regulation, andSREBP-2 links isoprenoid and adenosylcobalamin metabolism, demonstrating complex regulatory networks.[5]
Lipid Metabolism and Cardiovascular Health
Section titled “Lipid Metabolism and Cardiovascular Health”Lipid metabolism is a fundamental biological process with profound implications for cardiovascular health. Key biomolecules, including LDL-C, HDL-C, and triglycerides, are central to this process, and their concentrations are influenced by numerous genetic loci.[7]Dysregulation of these lipid levels can lead to pathophysiological processes such as polygenic dyslipidemia and increase the risk of coronary artery disease.[5] For example, the protein APOC3is critical in triglyceride metabolism, and its functional loss can significantly improve lipid profiles.[12] Enzymes like GALNT2modify proteins through O-linked glycosylation, which can have regulatory effects on proteins involved in HDL cholesterol and triglyceride metabolism, thereby affecting overall cardiovascular health.[5]At the tissue and organ level, these metabolic imbalances contribute to the development of subclinical atherosclerosis in major arterial territories and can impact echocardiographic dimensions and endothelial function.[14] The CSPG3 gene, encoding neurocan, a brain chondroitin sulfate proteoglycan, has also been implicated in lipid traits, suggesting a broader systemic involvement.[5]
Cellular Signaling and Homeostasis
Section titled “Cellular Signaling and Homeostasis”Cellular signaling pathways and regulatory networks are vital for maintaining metabolic homeostasis. Proteins known as human tribbles, for instance, are involved in controlling mitogen-activated protein kinase (MAPK) cascades, which are crucial signaling pathways regulating various cellular functions.[6] Disruptions in these cascades can have widespread effects on cellular processes. O-linked glycosylation, an enzymatic modification carried out by proteins like GALNT2, serves a significant regulatory role for many proteins, influencing their activity and interactions within the cell.[5] This post-translational modification can impact the function of proteins involved in lipid metabolism, thereby contributing to the maintenance or disruption of metabolic balance. Furthermore, the transcription factor SREBP-2 plays a role in linking isoprenoid and adenosylcobalamin metabolism, illustrating how key biomolecules integrate seemingly disparate metabolic pathways to maintain cellular health and function.[6]
Systemic Metabolic Interactions and Disease Development
Section titled “Systemic Metabolic Interactions and Disease Development”The interplay of genetic factors, molecular pathways, and cellular functions ultimately manifests in systemic metabolic interactions that influence disease development. Genome-wide association studies have identified loci associated with various metabolic traits, diabetes-related traits, and overall metabolite profiles in human serum, demonstrating the polygenic nature of these complex conditions.[15]The cumulative effect of common genetic variants contributes to conditions like polygenic dyslipidemia, where multiple genetic loci collectively influence lipid concentrations and disease risk.[5]The heritability of traits such as echocardiographic dimensions, brachial artery endothelial function, and treadmill exercise responses underscores the significant contribution of additive genetic effects to interindividual variation, influencing the predisposition to cardiovascular diseases.[1] These findings suggest that a complex network of genetic and biochemical factors contributes to the overall metabolic landscape, impacting systemic health and susceptibility to chronic diseases.
Impact on Cognitive Performance and Associations
Section titled “Impact on Cognitive Performance and Associations”Studies indicate that plasma vitamin B12 levels are associated with overall cognitive performance, a domain that encompasses various executive functions. Research conducted in the Nurses’ Health Study observed that women with lower plasma vitamin B12 levels demonstrated marginally worse cognitive performance when assessed across a global score derived from six cognitive tests.[11]This finding suggests a potential role for maintaining adequate nutritional status, particularly concerning vitamin B12, in supporting cognitive health and the integrity of executive processes. Furthermore, a combined deficiency of both folate and vitamin B12 was linked to the lowest cognitive performance, highlighting the synergistic impact of these essential nutrients on brain function and potentially, the efficiency of executive functions.[11]
Diagnostic and Prognostic Value
Section titled “Diagnostic and Prognostic Value”The observed association between vitamin B12 and folate status and cognitive performance suggests a diagnostic utility for these nutritional biomarkers in assessing the risk for cognitive impairment, which often manifests with deficits in executive functions. Monitoring plasma vitamin B12 levels, especially in vulnerable populations such as women, could serve as an early indicator for individuals who might be predisposed to cognitive decline.[11]From a prognostic perspective, identifying and addressing deficiencies in these vitamins could potentially mitigate or slow the progression of cognitive decline, thereby influencing long-term patient outcomes related to daily functioning and overall quality of life.[11]
Risk Stratification and Personalized Care
Section titled “Risk Stratification and Personalized Care”Given the established link between vitamin B12 and folate deficiency and compromised cognitive performance, these nutritional biomarkers are relevant for effective risk stratification in clinical practice. Individuals, particularly women, exhibiting low plasma vitamin B12 levels or combined deficiencies may be identified as a high-risk group for developing compromised cognitive abilities, including key executive functions.[11] This understanding allows for more personalized medicine approaches, where targeted nutritional assessment and intervention, such as appropriate supplementation, could be considered as proactive prevention strategies to support cognitive health and potentially improve treatment response in those already experiencing cognitive challenges.[11]
Frequently Asked Questions About Executive Function Measurement
Section titled “Frequently Asked Questions About Executive Function Measurement”These questions address the most important and specific aspects of executive function measurement based on current genetic research.
1. Why is it so hard for me to stop scrolling my phone, even when I know I should?
Section titled “1. Why is it so hard for me to stop scrolling my phone, even when I know I should?”That’s a common struggle related to inhibitory control, a key executive function. Genetic variations can influence the efficiency of brain networks, particularly in your prefrontal cortex, that are responsible for suppressing impulses. While environmental factors play a huge role, your unique genetic makeup can make resisting immediate gratification more challenging for you than for others.
2. My sibling seems to plan everything perfectly, but I’m always disorganized. Why the difference?
Section titled “2. My sibling seems to plan everything perfectly, but I’m always disorganized. Why the difference?”Individual differences in executive functions like planning and organization often have a genetic component. While you share many genes with your sibling, variations in specific genes can influence the development and function of brain regions critical for these abilities. Environmental influences and life experiences also shape how these genetic predispositions manifest.
3. Does my brain just get worse at focusing as I get older?
Section titled “3. Does my brain just get worse at focusing as I get older?”Age is indeed an environmental factor that can influence cognitive performance, including focus. While there’s a natural age-related decline in some executive functions, genetic variations can impact how resilient your brain is to these changes. Some people are genetically predisposed to maintain stronger executive function abilities into older age, while others may experience more pronounced shifts.
4. Can a DNA test tell me why I’m so forgetful sometimes?
Section titled “4. Can a DNA test tell me why I’m so forgetful sometimes?”Genetic tests are becoming more advanced, and they can identify variations linked to overall brain health and certain cognitive predispositions. However, executive functions like working memory (which impacts forgetfulness) are complex traits influenced by many genes, each with small effects, plus environmental factors. A DNA test might offer insights into general predispositions, but it won’t give a definitive “why” for everyday forgetfulness, nor is it a diagnostic tool for it.
5. I try to switch tasks at work, but my brain feels stuck. Is that just me?
Section titled “5. I try to switch tasks at work, but my brain feels stuck. Is that just me?”This feeling of being “stuck” when switching tasks relates to cognitive flexibility. Genetic variations can influence the efficiency of brain circuits involved in adapting to new rules or shifting between different mental sets. For some, these genetic influences might make cognitive transitions feel more effortful, even with conscious effort.
6. Will my kids inherit my struggles with self-control?
Section titled “6. Will my kids inherit my struggles with self-control?”There is a heritable component to executive functions, including self-control. This means your genetic makeup can contribute to a predisposition for certain cognitive strengths or challenges, which can be passed on to your children. However, executive function is a complex trait, and environmental factors like upbringing, education, and lifestyle play a very significant role in how these genetic tendencies develop.
7. Does stress actually make me worse at making decisions, or is that just an excuse?
Section titled “7. Does stress actually make me worse at making decisions, or is that just an excuse?”It’s definitely not just an excuse! Stress is a significant environmental factor that can profoundly impact your executive functions, including decision-making. Your genetic variations can influence how your brain’s neurotransmitter systems (like dopamine and norepinephrine) respond to stress, making some individuals more vulnerable to stress-induced impairments in cognitive abilities.
8. Why do some people seem to multitask effortlessly while I get overwhelmed easily?
Section titled “8. Why do some people seem to multitask effortlessly while I get overwhelmed easily?”The ability to effectively manage multiple streams of information or tasks draws heavily on working memory and cognitive flexibility. Genetic variations contribute to individual differences in the capacity and efficiency of these core cognitive processes. What might seem effortless for one person could be genuinely overwhelming for another due to these underlying genetic influences on brain function.
9. Does my family’s ethnic background affect how my brain plans things?
Section titled “9. Does my family’s ethnic background affect how my brain plans things?”Yes, the genetic architecture of complex traits, including executive function, can vary across different ancestral groups. Much of the large-scale genetic research has historically focused on populations of European ancestry. This means that genetic variants identified in one population might not have the same effect, or even be present, in others, impacting how we understand planning abilities across diverse backgrounds.
10. Can exercise or diet really improve my focus if it’s “in my genes”?
Section titled “10. Can exercise or diet really improve my focus if it’s “in my genes”?”Absolutely! While genetics contribute to the baseline of your executive functions, including focus, environmental and lifestyle factors like exercise and diet are powerful modulators. They can influence neurotransmitter systems and brain health, potentially optimizing the expression of your genetic predispositions. You can definitely strengthen your cognitive abilities through healthy habits, regardless of your genetic starting point.
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] 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, suppl. 1, 2007, S2.
[2] Benjamin, EJ et al. “Genome-wide association with select biomarker traits in the Framingham Heart Study.” BMC Med Genet, vol. 8 Suppl 1, 2007, p. S9.
[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, 2007.
[4] Pare, Guillaume et al. “Novel association of ABO histo-blood group antigen with soluble ICAM-1: results of a genome-wide association study of 6,578 women.” PLoS Genetics, vol. 4, no. 7, 2008.
[5] Kathiresan, S et al. “Common variants at 30 loci contribute to polygenic dyslipidemia.” Nat Genet, vol. 41, no. 1, 2009, pp. 56–65.
[6] 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. 161-169.
[7] Aulchenko, Y. S., et al. “Loci influencing lipid levels and coronary heart disease risk in 16 European population cohorts.” Nat Genet, vol. 40, no. 1, 2008, pp. 60-68.
[8] Melzer, D et al. “A genome-wide association study identifies protein quantitative trait loci (pQTLs).” PLoS Genet, vol. 4, no. 5, 2008, p. e1000072.
[9] Wilk, JB et al. “Framingham Heart Study genome-wide association: results for pulmonary function measures.” BMC Med Genet, vol. 8 Suppl 1, 2007, p. S8.
[10] Wallace, C et al. “Genome-wide association study identifies genes for biomarkers of cardiovascular disease: serum urate and dyslipidemia.”Am J Hum Genet, vol. 82, no. 1, 2008, pp. 139–149.
[11] Hazra, A, et al. “Common variants of FUT2 are associated with plasma vitamin B12 levels.”Nat Genet, PMID: 18776911.
[12] Pollin, T. I., et al. “A null mutation in human APOC3 confers a favorable plasma lipid profile and apparent cardioprotection.” Science, vol. 322, no. 5904, 2008, pp. 1084-1087.
[13] Burkhardt, R., et al. “Common SNPs in HMGCR in micronesians and whites associated with LDL-cholesterol levels affect alternative splicing of exon13.” Arterioscler Thromb Vasc Biol, vol. 28, no. 12, 2008, pp. 2090-2096.
[14] 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, suppl. 1, 2007, S4.
[15] 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.