Susceptibility To Viral And Mycobacterial Infections
Individual responses to infectious agents vary widely, even among those with similar exposure levels. This variability, ranging from asymptomatic infection to severe disease, is influenced by a complex interplay of environmental factors, pathogen characteristics, and host genetics. Susceptibility to viral and mycobacterial infections refers to the predisposition of an individual to contract, develop severe symptoms from, or experience adverse outcomes following exposure to viruses (such as influenza, HIV, or SARS-CoV-2) and mycobacteria (such as Mycobacterium tuberculosis). Understanding the genetic components contributing to this susceptibility is crucial for public health and personalized medicine.
Biological Basis
Genetic variations within an individual's genome can profoundly impact the immune system's ability to detect, respond to, and clear pathogens. These variations can occur in genes encoding components of both the innate and adaptive immune systems. For instance, genetic polymorphisms in genes related to pathogen recognition receptors (e.g., Toll-like receptors), signaling molecules (e.g., interferons, cytokines like IL6 and TNF), antigen presentation (HLA genes), and T-cell or B-cell function can alter the efficacy of the immune response. Such genetic differences may affect how quickly a host can mount a defense, the strength and type of the immune response, or the ability of the pathogen to evade immune surveillance. Specific single nucleotide polymorphisms (SNPs) can modify protein structure, alter gene expression levels, or influence regulatory pathways, thereby modulating an individual's vulnerability to infection.
Clinical Relevance
Identifying genetic factors that influence susceptibility has significant clinical implications. It can help pinpoint individuals at higher risk for developing severe forms of viral or mycobacterial diseases, allowing for targeted preventive measures, such as enhanced surveillance, early intervention, or personalized vaccination strategies. Genetic insights can also explain differences in disease progression, treatment response, and the likelihood of developing complications. For example, understanding an individual's genetic profile could inform the choice of antiviral medications, predict the likelihood of developing active tuberculosis after latent infection, or identify those prone to adverse reactions to specific therapies. This knowledge paves the way for more precise diagnostic tools and individualized treatment plans.
Social Importance
The genetic basis of susceptibility to viral and mycobacterial infections holds broad social importance, impacting public health policy and efforts to reduce health disparities. Variations in genetic predisposition can contribute to observed differences in disease burden and severity across diverse populations and geographic regions. By elucidating these genetic factors, public health initiatives can be better tailored, including the development of more effective screening programs, targeted vaccine development, and culturally sensitive health education campaigns. Ultimately, a deeper understanding of genetic susceptibility is vital for developing comprehensive strategies to combat global infectious disease threats and promote health equity worldwide.
Methodological and Statistical Constraints
Research into susceptibility to viral and mycobacterial infections often faces inherent methodological and statistical challenges that can influence the scope and interpretation of findings. Genome-wide association studies (GWAS), while powerful for identifying common genetic variants, are inherently limited in their ability to capture low-frequency or rare host variations that may play a significant role in disease causation, necessitating large-scale genome sequencing efforts for their discovery. [1] Furthermore, the selection and quality control of genetic markers can impact results, as studies often exclude single nucleotide polymorphisms (SNPs) with low minor allele frequency (MAF) or poor genotyping call rates, potentially overlooking relevant genetic signals. [2] Imputation quality thresholds, where SNPs with an imputation quality R2 score below a certain value are excluded, can also lead to a loss of potentially informative variants. [3]
The design of GWAS platforms, which utilize a subset of all known SNPs, means that some genes or genomic regions may not be adequately covered, leading to a failure to detect true associations or comprehensively study candidate genes. [4] Statistical power is also a critical consideration, particularly for complex traits like infection susceptibility; for instance, recruiting sufficient numbers of well-characterized individuals, such as those highly exposed but uninfected, can be challenging, thus limiting the power of studies to detect subtle genetic effects. [5] Moreover, meta-analyses, while increasing power, can present complexities, as combining data from diverse populations can weaken associations if genetic effects have opposite directions across groups, impacting the overall interpretability of findings. [6]
Generalizability and Phenotypic Measurement Challenges
The generalizability of findings across diverse populations is a significant limitation in genetic studies of infection susceptibility, as many studies are conducted in ethnically homogeneous cohorts, such as those predominantly of European or African ancestry. [7] Genetic architecture, including patterns of linkage disequilibrium (LD), can vary substantially between populations, meaning that findings from one group may not directly translate to another, particularly when comparing populations with different ancestral backgrounds. [1] This demographic specificity can restrict the broader applicability of identified genetic risk factors, highlighting the need for more diverse and inclusive research cohorts.
Phenotypic measurement and characterization also pose considerable challenges, particularly for complex traits like infection susceptibility, where precise quantification of exposure is crucial. For example, studies may lack detailed information on individual exposure levels, sexual orientation, or intravenous drug use, which are critical epidemiological modifiers of infection risk. [5] Without such granular data, it becomes difficult to fully disentangle genetic predispositions from environmental or behavioral factors that contribute to susceptibility. Additionally, analyses might be limited by design choices, such as sex-pooled analyses, which could obscure sex-specific genetic associations that are only present in males or females. [4]
Unaccounted Genetic and Environmental Variation
A substantial portion of the heritability for complex traits, including susceptibility to infections, often remains unexplained by common genetic variants identified through GWAS, pointing to the phenomenon of "missing heritability." This gap suggests that other forms of genetic variation, such as rare variants, copy number variations, or gene-gene interactions, which are not readily captured by standard GWAS methodologies, likely contribute significantly. [1] The current scope of GWAS platforms may not provide sufficient coverage to detect all relevant genetic loci, leaving many potential genetic determinants unexplored. [4]
Furthermore, environmental factors and gene-environment interactions represent crucial, yet often unmeasured, confounders in studies of infection susceptibility. Lifestyle choices, socioeconomic status, nutritional deficiencies, and exposure to pathogens or other environmental stressors can profoundly modify an individual's risk of infection, interacting with genetic predispositions in complex ways. [5] Without comprehensive data on these intricate environmental influences and their interplay with genetic factors, the full picture of infection susceptibility remains incomplete. This highlights a persistent knowledge gap regarding the dynamic relationship between an individual's genetic makeup and their lived environment in determining disease outcomes.
Variants
Genetic variants play a crucial role in shaping an individual's susceptibility and response to various infections, including viral and mycobacterial pathogens. These single nucleotide polymorphisms (SNPs) can reside within genes, altering protein function or expression, or in non-coding regions, influencing gene regulation. Understanding these variations helps to elucidate the complex interplay between human genetics and immune defense. Research efforts continue to identify specific genetic markers that contribute to host resistance or vulnerability to infectious diseases, often through large-scale genome-wide association studies (GWAS). [5]
Variants in genes of the Major Histocompatibility Complex (MHC), such as HLA-DQB2 (rs7453920) and HLA-DPB1 (rs9277535), are central to the immune system's ability to recognize and respond to pathogens. These HLA class II genes encode proteins that present pathogen-derived peptides to T-helper cells, initiating a specific adaptive immune response. Variations in these genes, such as rs7453920 in HLA-DQB2 and rs9277535 in HLA-DPB1, can influence the repertoire of peptides that can be presented, thereby affecting the strength and specificity of the immune response against viral infections like HIV-1 or mycobacterial infections such as tuberculosis. Such genetic differences can modulate the course of infection, influencing viral load set points or the ability to clear pathogens. [1]
Beyond antigen presentation, other genetic variations can affect immune function through diverse mechanisms. For instance, the KDM4C gene (KDM4C rs16925298) encodes a histone demethylase, an enzyme that regulates gene expression by modifying chromatin structure. A variant like rs16925298 could alter the expression of immune-related genes, impacting the development and function of immune cells. Similarly, genes involved in metabolism, like HSD17B8 (HSD17B8 - MIR219A1: rs421446) and CYP7B1 (CYP7B1 rs10808739), play roles in steroid and bile acid synthesis, pathways that can indirectly influence immune cell activity and inflammatory responses. Alterations in these metabolic pathways due to variants such as rs421446 or rs10808739 may affect the host's ability to mount an effective defense against infections. [8] The BICRA gene (BICRA rs3745760), involved in chromatin remodeling, could also influence immune gene expression, while LZTS1 (LZTS1 - TMEM97P2: rs7000921) plays a role in cell cycle regulation, potentially impacting immune cell proliferation. Variants in such genes, including rs3745760 and rs7000921, may lead to subtle but significant changes in immune cell behavior and overall immune competence. [2]
Variants in genes that influence cell signaling, structural integrity, or non-coding RNA pathways can also modulate infection susceptibility. For example, FRMPD1 (FRMPD1 rs4878712) is involved in cell signaling and cytoskeletal organization, processes critical for immune cell migration and pathogen uptake. SPOCK1 (SPOCK1 rs1229741) encodes a proteoglycan that contributes to the extracellular matrix, potentially affecting immune cell trafficking and tissue remodeling during infection. Furthermore, non-coding RNAs like microRNAs, represented by MIR219A1 (part of HSD17B8 - MIR219A1: rs421446) and MIR8074 (MIR8074 - SIGLEC22P: rs3987765), regulate gene expression post-transcriptionally. Variants like rs421446 or rs3987765 could alter microRNA function, leading to dysregulation of immune pathways. The pseudogenes TMEM97P2 (part of LZTS1 - TMEM97P2: rs7000921) and SIGLEC22P (part of MIR8074 - SIGLEC22P: rs3987765) may also play regulatory roles, for example, by producing non-coding RNAs or influencing the expression of nearby functional genes, thus indirectly affecting the host's defense mechanisms . [5], [8]
Key Variants
| RS ID | Gene | Related Traits |
|---|---|---|
| rs7000921 | LZTS1 - TMEM97P2 | susceptibility to viral and mycobacterial infections |
| rs7453920 | HLA-DQB2 | chronic hepatitis B virus infection lymphoma hepatitis B virus infection susceptibility to viral and mycobacterial infections |
| rs421446 | HSD17B8 - MIR219A1 | susceptibility to viral and mycobacterial infections |
| rs4878712 | FRMPD1 | susceptibility to viral and mycobacterial infections |
| rs1229741 | SPOCK1 | susceptibility to viral and mycobacterial infections gut microbiome measurement, breastfeeding duration |
| rs9277535 | HLA-DPB1 | chronic hepatitis B virus infection hepatitis B virus infection susceptibility to viral and mycobacterial infections response to vaccine |
| rs16925298 | KDM4C | susceptibility to viral and mycobacterial infections |
| rs3987765 | MIR8074 - SIGLEC22P | susceptibility to viral and mycobacterial infections |
| rs3745760 | BICRA | susceptibility to viral and mycobacterial infections |
| rs10808739 | CYP7B1 | susceptibility to viral and mycobacterial infections |
Defining Susceptibility to HIV-1 Infection
Susceptibility to HIV-1 infection fundamentally refers to an individual's intrinsic likelihood of acquiring the Human Immunodeficiency Virus type 1. This trait is often characterized through "HIV infection status" [5] or the process of "HIV-1 acquisition" [1] distinguishing individuals who become infected from those who remain uninfected despite exposure. The concept also encompasses "HIV-1 control," which denotes the host's capacity to manage viral replication and disease progression following infection. [2]
Operationally, susceptibility is assessed by classifying individuals based on their "HIV-1 seropositive" status, indicating the presence of HIV antibodies. [1] Research frequently involves "seroconverting couples" to study transmission dynamics and host factors. [1] A critical aspect of defining and measuring susceptibility involves considering "quantified virus exposure," which utilizes metrics such as "HIV-1 exposure risk scores" or specific "HIV-1 exposure cutoff" values to standardize exposure levels among study participants. [1]
Genetic and Environmental Factors Influencing HIV-1 Susceptibility
The susceptibility to HIV-1 infection is significantly influenced by "host determinants," including specific "genetic variants" [2] or "common human genetic variants". [5] A well-characterized genetic factor is the CCR5 Δ32 deletion (rs333), which is a "genic deletion" known to be associated with aspects of HIV-1 control. [2] Genetic research aims to identify these variants and elucidate their mechanisms in modulating an individual's risk of infection or the trajectory of the disease.
Beyond inherent genetic predisposition, environmental and behavioral factors play a crucial role in determining exposure and, consequently, infection risk. Studies rigorously account for "quantified virus exposure," which includes variables such as "any unprotected sex," the circumcision status of the "male uninfected partner," and the "uninfected partner age <25 yrs". [1] Furthermore, the "infected partner plasma viral RNA" level is a significant determinant of transmission risk [1] necessitating the establishment of an "HIV-1 exposure cutoff" to ensure robust susceptibility analyses. [1]
Methodological Approaches and Criteria in Genetic Susceptibility Studies
Genetic susceptibility to HIV-1 is typically investigated using "genome-wide association analysis" (GWAS), a powerful approach that systematically searches for associations between "HIV infection status" and "single-marker genotypes" across the entire genome. [5] These analyses commonly employ "logistic regression in an additive genetic model," incorporating adjustments for confounding variables such as age, gender, and population structure. [5] To account for "population stratification," methods like "EIGENSTRAT" are utilized, which leverage "principal component analysis" to model and correct for ancestral differences among study participants. [5]
In terms of statistical criteria and nomenclature, controlling for "multiple testing" in GWAS is essential, often achieved through adjustments like "Bonferroni correction". [5] This correction may follow a "linkage disequilibrium pruning procedure" to reduce the number of entirely dependent markers. [5] Key genetic terminology includes "minor allele frequency" (MAF), which describes the prevalence of the less common allele at a specific genetic locus. [4] While a universally "standard method" or "well defined" cut-off p-value for statistical significance in GWAS remains elusive [9] proposed thresholds, such as p = 4.26x10^-7 derived from Bayesian approaches, serve as valuable "rough reference[s]" for identifying significant genetic associations. [9]
Genetic Predisposition to Infection
Susceptibility to viral and mycobacterial infections is significantly influenced by an individual's genetic makeup, encompassing both specific inherited variants and the cumulative effect of multiple genes. For instance, a well-documented genetic factor is the _CCR5_ delta32 deletion (rs333), which confers resistance to HIV-1 infection by preventing the virus from entering host cells. [2] Similarly, polymorphisms within the _MBL_ (Mannose-binding lectin) gene, which plays a critical role in innate immunity, have been shown to impact susceptibility to HIV-1 infection. [10]
Beyond these specific Mendelian-like effects, the broader landscape of genetic risk involves numerous common and rare variants, contributing to a polygenic risk profile. Genome-wide association studies (GWAS) have identified common genetic variants associated with disease outcomes, but they also highlight that low-frequency or rare host variations are important sources of human disease causation that are not easily captured by current GWAS methods and necessitate large-scale genome sequencing efforts. [1] Furthermore, genetic variation in genes like _IL28B_ has been found to predict treatment-induced viral clearance for infections such as hepatitis C, suggesting a role for host genetics in the immune response and resolution of viral challenges. [11]
Environmental Exposure and Behavioral Modifiers
Environmental factors play a critical role in determining an individual's risk of acquiring viral and mycobacterial infections, often interacting with genetic predispositions. For HIV-1, the level of exposure is a primary determinant of infection risk, with quantified exposure levels modifying the risk of sexual transmission by up to 300-fold. [1] This underscores the profound impact of the environment and specific exposure events on disease acquisition.
Key environmental and behavioral factors influencing transmission risk include the plasma HIV-1 RNA levels in the transmitting partner, which directly correlates with viral load exposure. [1] Additional epidemiological, biological, and behavioral elements, such as the circumcision status of uninfected male partners and the frequency of unprotected sexual encounters, also significantly contribute to the overall risk of acquiring HIV-1. [1] These factors collectively highlight how external circumstances and individual choices can dramatically alter an individual's probability of infection, regardless of underlying genetic vulnerabilities.
Gene-Environment Interactions in Susceptibility
The interplay between an individual's genetic background and their environmental exposures represents a complex dynamic that shapes susceptibility to viral and mycobacterial infections. Research designs, such as studies involving HIV-1 serodiscordant couples with carefully quantified virus exposure, are specifically employed to control for epidemiological modifiers of HIV-1 acquisition. [1] This approach allows for a more precise isolation of genetic factors by accounting for the varying levels of environmental challenge, thereby revealing how genetic predispositions manifest under different exposure scenarios.
Without accurate quantification of exposure, misclassification of infection phenotypes can occur, leading to a reduced ability to detect relevant common genetic variants. [1] This suggests that genetic susceptibility is not static but is expressed or masked depending on the intensity and nature of environmental triggers. For example, a genetic resistance factor might only provide a protective advantage when an individual is actually exposed to the pathogen, illustrating how inherited traits modify risk within a specific environmental context.
Host Immune Recognition and Pathogen Entry
Susceptibility to viral and mycobacterial infections is significantly influenced by the host's ability to recognize pathogens and prevent their entry into cells. A key molecular player in viral infection, specifically HIV-1, is the chemokine receptor CCR5. This protein acts as a co-receptor for HIV-1 entry into host cells, and a common genetic variant, a 32-base pair deletion in the CCR5 gene, known as CCR5_Δ32 (rs333), is associated with altered susceptibility to HIV-1 infection . This pathway is essential for T helper 17 (Th17) cell differentiation and function, which are crucial for defense against extracellular pathogens. Furthermore, SOCS1 (Suppressor of Cytokine Signaling 1) acts as a critical negative feedback regulator within these pathways, being cytokine-inducible and dampening excessive immune activation, thereby preventing immunopathology. [8] Its expression can be induced by cytokines like IL2, IL3, erythropoietin, and interferon-gamma, highlighting its central role in modulating the intensity and duration of inflammatory processes. [8]
Host-Pathogen Interaction at the Cellular Surface
The initial contact between host cells and pathogens often dictates the success of an infection, with host cell surface molecules playing a crucial role. For instance, the FUT2 gene is responsible for the expression of Lewis human blood group antigens on the surface of epithelial cells and in various body fluids. [8] Genetic variations in FUT2 have been linked to an altered susceptibility to infections, including Norovirus and Helicobacter pylori, by influencing the availability of these surface receptors for pathogen attachment. [8] Similarly, polymorphisms in the CCR5 gene have been implicated in susceptibility to viral infections, specifically HIV-1, by affecting the entry mechanisms pathogens utilize to infect host cells. [1]
Cellular Stress Response and Protein Homeostasis
Host defense against infection also relies on robust cellular mechanisms to combat stress and maintain protein integrity. PRDX5, which encodes Peroxiredoxin-5, is a member of the peroxiredoxin family of antioxidant enzymes that are vital for reducing hydrogen peroxide and alkyl hydroperoxides. [8] This enzymatic activity is crucial for protecting cells from oxidative damage, which is a common consequence of inflammatory processes and immune responses to infection. [8] Additionally, the heat-shock protein 90 (HSP90) molecular chaperone system, assisted by cochaperones like CDC37 and STI1, is fundamental for the proper folding and stabilization of many client proteins, including key signaling molecules like JAK1 and JAK2. [8] The integrity of this chaperone system is essential for maintaining the functionality of immune signaling pathways and cellular resilience during infection. [8]
Integrated Immunological Networks and Disease Susceptibility
Susceptibility to viral and mycobacterial infections arises from the complex integration and crosstalk among various molecular pathways rather than isolated mechanisms. The interconnectedness of genes involved in the IL23/Th17 signaling pathway, such as IL12B, IL23R, TYK2, JAK2, SOCS1, and STAT3, exemplifies how multiple components collaborate to mount an effective immune response. [8] Dysregulation within these tightly regulated networks, whether through genetic variants affecting gene expression or protein function, can impair the host's ability to clear pathogens or lead to excessive inflammation. This systems-level interaction, where cellular stress responses, immune signaling, and host-pathogen receptor interactions are all interwoven, ultimately determines the emergent properties of host susceptibility and disease outcome.
Clinical Relevance
Understanding an individual's genetic susceptibility to viral and mycobacterial infections holds significant clinical relevance, influencing risk assessment, disease management, and public health strategies. While specific genetic determinants can vary across different pathogens, insights gained from studies on viruses like HIV-1 highlight the potential for personalized medicine approaches. These insights encompass identifying individuals at heightened risk, predicting disease trajectory, and optimizing therapeutic interventions.
Genetic Determinants of Viral Susceptibility and Acquisition
Host genetic factors significantly influence an individual's susceptibility to acquiring viral infections, exemplified by human immunodeficiency virus type 1 (HIV-1). Polymorphisms in genes such as CCR5 and mannose-binding lectin (MBL) have been identified as key determinants impacting HIV-1 infection risk ([1] ). This genetic insight provides diagnostic utility for risk assessment, enabling clinicians to identify high-risk individuals and tailor personalized prevention strategies. Understanding these genetic predispositions is crucial for developing targeted interventions and public health initiatives to reduce viral transmission.
Prognostic Value in Viral Disease Progression and Control
Host genetic factors play a crucial role in predicting the course of viral infections, including HIV-1 disease progression and the establishment of viral set points ([1] ). Studies investigating host determinants of HIV-1 control in specific populations, such as African Americans, have provided insights into factors influencing viral load and long-term disease outcomes ([2] ). This prognostic information helps in anticipating individual patient trajectories, guiding expectations for disease progression, and informing discussions about long-term implications. Such genetic insights can also predict treatment response, allowing for a more nuanced approach to patient management.
Informing Personalized Management and Monitoring Strategies
The identification of host genetic determinants influencing susceptibility and control of viral infections has significant implications for personalized patient care. Genetic information can guide treatment selection by identifying patients who might respond differently to specific antiviral therapies based on their genetic profile ([2] ). Furthermore, these insights enable the development of more effective prevention strategies by targeting high-risk individuals for intensive counseling or prophylactic measures ([1] ). Finally, understanding genetic susceptibility informs the design of monitoring strategies, allowing for closer surveillance of individuals predisposed to severe disease or treatment complications, thereby optimizing patient outcomes.
Frequently Asked Questions About Susceptibility To Viral And Mycobacterial Infections
These questions address the most important and specific aspects of susceptibility to viral and mycobacterial infections based on current genetic research.
1. My sibling got really sick with the flu, but I barely felt it. Why the difference?
Your genetic makeup plays a big role in how your immune system responds to infections. Variations in genes related to immune signaling or T-cell function can mean you mount a quicker, more effective defense against a virus like the flu compared to your sibling, even with similar exposure.
2. Why do some people seem to catch every bug going around, but others rarely get sick?
It's often due to genetic variations that influence your immune system's strength and efficiency. Some individuals have genetic profiles that make their immune systems better at recognizing and clearing pathogens, while others might have variations that make them more vulnerable to contracting infections.
3. If I'm exposed to a virus, will I get as sick as my friend did?
Not necessarily. Your genetic profile significantly influences how severely you react to an infection. Variations in genes like IL6 or TNF can affect the intensity of your immune response, determining whether you develop mild symptoms or a more severe illness and complications.
4. Does my family's ethnic background affect how I handle infections?
Yes, genetic factors influencing infection susceptibility can vary significantly across different ancestral populations. Your background might mean you have different genetic predispositions or immune responses compared to someone from another group, impacting your risk and disease progression.
5. Can genetics tell me if a vaccine will work well for me?
Potentially, yes. Understanding your genetic profile can help predict how effectively your immune system will respond to a vaccine. This insight could lead to personalized vaccination strategies, ensuring you receive the most effective protection based on your unique genetic makeup.
6. I was exposed to TB years ago but never got sick. Does my body naturally fight it better?
It's very possible. Genetic factors can influence whether a latent Mycobacterium tuberculosis infection progresses to active disease. Your genes might give your immune system an advantage in keeping the bacteria under control, preventing you from developing symptoms.
7. Does being stressed all the time make me more likely to get sick, or is that a myth?
It's not a myth; stress can absolutely impact your susceptibility. While genetics set a baseline for your immune response, environmental factors like chronic stress, poor nutrition, or lifestyle choices can significantly influence how well your immune system functions and your overall vulnerability to infection.
8. Could a DNA test tell me if I'm extra vulnerable to certain infections?
Yes, identifying specific genetic factors through testing can pinpoint individuals at higher risk for developing severe forms of viral or mycobacterial diseases. This knowledge can help guide targeted preventive measures and early interventions for you.
9. Why do some people recover quickly from infections, but I take ages to feel better?
Your genes play a role in how quickly your body clears pathogens and repairs damage. Genetic differences can influence the speed and efficiency of your immune response, affecting disease progression, the likelihood of complications, and ultimately, your recovery time.
10. My coworker got COVID and was fine, but I was really sick. Why were our experiences so different?
Individual genetic variations significantly impact how your immune system responds to viruses like SARS-CoV-2. Differences in genes affecting pathogen recognition, immune signaling, or the strength of your inflammatory response can lead to vastly different disease severities, even with the same virus.
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
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[2] Pelak, K, et al. "Host determinants of HIV-1 control in African Americans." J Infect Dis, vol. 201, no. 11, 2010, pp. 1656-61.
[3] Huang, J., et al. "Cross-disorder genomewide analysis of schizophrenia, bipolar disorder, and depression." Am J Psychiatry, vol. 167, no. 10, 2010, pp. 1228-1238.
[4] Yang, Q, et al. "Genome-wide association and linkage analyses of hemostatic factors and hematological phenotypes in the Framingham Heart Study." BMC Med Genet, vol. 8, 2007, p. 55.
[5] Petrovski, S, et al. "Common human genetic variants and HIV-1 susceptibility: a genome-wide survey in a homogeneous African population." AIDS, vol. 25, no. 3, 2011, pp. 331-7.
[6] Zuo, L, et al. "Genome-wide search for replicable risk gene regions in alcohol and nicotine co-dependence." Am J Med Genet B Neuropsychiatr Genet, vol. 159B, no. 4, 2012, pp. 433-46.
[7] Ferrucci, L., et al. "Common variation in the beta-carotene 15,15'-monooxygenase 1 gene affects circulating levels of carotenoids: a genome-wide association study." Am J Hum Genet, vol. 84, no. 1, 2009, pp. 123-133.
[8] Ellinghaus, D, et al. "Combined analysis of genome-wide association studies for Crohn disease and psoriasis identifies seven shared susceptibility loci." Am J Hum Genet, vol. 90, no. 4, 2012, pp. 683-97.
[9] Liu, Y. Z., et al. "Powerful bivariate genome-wide association analyses suggest the SOX6 gene influencing both obesity and osteoporosis phenotypes in males." PLoS One, vol. 4, no. 8, 2009, p. e6730. PMID: 19714249.
[10] Pastinen, T., et al. "Contribution of the CCR5 and MBL genes to susceptibility to HIV type 1 infection in the Finnish population." AIDS Res Hum Retroviruses, vol. 14, no. 8, 1998, pp. 695–698.
[11] Ge, D., Fellay, J., Thompson, A. J., et al. "Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance." Nature, vol. 461, no. 7262, 2009, pp. 399-401.