scholarly journals Genome Wide Meta-analysis Highlights the Role of Genetic Variation in RARRES2 in the Regulation of Circulating Serum Chemerin

PLoS Genetics ◽  
2014 ◽  
Vol 10 (12) ◽  
pp. e1004854 ◽  
Author(s):  
Anke Tönjes ◽  
Markus Scholz ◽  
Jana Breitfeld ◽  
Carola Marzi ◽  
Harald Grallert ◽  
...  
Keyword(s):  
Genetic Variation ◽  
Meta Analysis ◽  
Genome Wide

scholarly journals Genome-wide study identifies association between HLA-B*55:01 and penicillin allergy

2020 ◽  
Author(s):  
Kristi Krebs ◽  
Jonas Bovijn ◽  
Maarja Lepamets ◽  
Jenny C Censin ◽  
Tuuli Jürgenson ◽  
...  
Keyword(s):  
Genetic Variation ◽  
Meta Analysis ◽  
Strong Association ◽  
Hla Typing ◽  
Penicillin Allergy ◽  
P Value ◽  
Hypersensitivity Reactions ◽  
Hla Association ◽  
Genome Wide

AbstractBackgroundHypersensitivity reactions to drugs are often unpredictable and can be life-threatening, underscoring a need for understanding their underlying mechanisms and risk factors. The extent to which germline genetic variation influences the risk of commonly reported drug allergies such as penicillin allergy remains largely unknown.MethodsWe extracted data from the electronic health records of 52,000 Estonian and 500,000 UK biobank participants to study the role of genetic variation in the occurrence of penicillin hypersensitivity reactions. We used imputed SNP to HLA typing data from up to 22,554 and 488,377 individuals from the Estonian and UK cohorts, respectively, to further fine-map the human leukocyte antigen (HLA) association and replicated our results in two additional cohorts involving a total of 1.14 million individuals.ResultsGenome-wide meta-analysis of penicillin allergy revealed a significant association located in the HLA region on chromosome 6. The signal was further fine-mapped to the HLA-B*55:01 allele (OR 1.47 95% CI 1.37-1.58, P-value 4.63×10-26) and confirmed by independent replication in two cohorts. The meta-analysis of all four cohorts in the study revealed a strong association of HLA-B*55:01 allele with penicillin allergy (OR 1.33 95% CI 1.29-1.37, P-value 2.23×10-72). In silico follow-up suggests a potential effect on T lymphocytes at HLA-B*55:01.ConclusionWe present the first robust evidence for the role of an allele of the major histocompatibility complex (MHC) I gene HLA-B in the occurrence of penicillin allergy.

scholarly journals The crucial role of genome-wide genetic variation in conservation

2021 ◽  
Vol 118 (48) ◽  
pp. e2104642118
Author(s):  
Marty Kardos ◽  
Ellie E. Armstrong ◽  
Sarah W. Fitzpatrick ◽  
Samantha Hauser ◽  
Philip W. Hedrick ◽  
...  
Keyword(s):  
Genetic Variation ◽  
Environmental Changes ◽  
Population Viability ◽  
Adaptive Potential ◽  
Biodiversity Crisis ◽  
Genome Wide ◽  
Simulation Based ◽  
Functional Genetic Variation

The unprecedented rate of extinction calls for efficient use of genetics to help conserve biodiversity. Several recent genomic and simulation-based studies have argued that the field of conservation biology has placed too much focus on conserving genome-wide genetic variation, and that the field should instead focus on managing the subset of functional genetic variation that is thought to affect fitness. Here, we critically evaluate the feasibility and likely benefits of this approach in conservation. We find that population genetics theory and empirical results show that conserving genome-wide genetic variation is generally the best approach to prevent inbreeding depression and loss of adaptive potential from driving populations toward extinction. Focusing conservation efforts on presumably functional genetic variation will only be feasible occasionally, often misleading, and counterproductive when prioritized over genome-wide genetic variation. Given the increasing rate of habitat loss and other environmental changes, failure to recognize the detrimental effects of lost genome-wide genetic variation on long-term population viability will only worsen the biodiversity crisis.

scholarly journals The crucial role of genome-wide genetic variation in conservation

2021 ◽  
Author(s):  
Martin Kardos ◽  
Ellie Armstrong ◽  
Sarah W Fitzpatrick ◽  
Samantha Hauser ◽  
Philip Hedrick ◽  
...  
Keyword(s):  
Genetic Variation ◽  
Environmental Changes ◽  
Population Viability ◽  
Adaptive Potential ◽  
Biodiversity Crisis ◽  
Genome Wide ◽  
Simulation Based ◽  
Functional Genetic Variation

The unprecedented rate of extinction calls for efficient use of genetics to help conserve biodiversity. Several recent genomic and simulation-based studies have argued that the field of conservation biology has placed too much focus on the conservation of genome-wide genetic variation, and that this approach should be replaced with another that focuses instead on managing the subset of functional genetic variation that is thought to affect fitness. Here, we critically evaluate the feasibility and likely benefits of this approach in conservation. We find that population genetics theory and empirical results show that the conserving genome-wide genetic variation is generally the best approach to prevent inbreeding depression and loss of adaptive potential from driving populations towards extinction. Focusing conservation efforts on presumably functional genetic variation will only be feasible occasionally, often misleading, and counterproductive when prioritized over genome-wide genetic variation. Given the increasing rate of habitat loss and other environmental changes, failure to recognize the detrimental effects of lost genome-wide variation on long-term population viability will only worsen the biodiversity crisis.

scholarly journals Genetic Susceptibility Loci for Childhood Acute Lymphoblastic Leukemia Among Japanese

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3731-3731
Author(s):  
Kevin Y Urayama ◽  
Masatoshi Takagi ◽  
Takahisa Kawaguchi ◽  
Keitaro Matsuo ◽  
Yoichi Tanaka ◽  
...  
Keyword(s):  
Genetic Variation ◽  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Study Group ◽  
Susceptibility Loci ◽  
East Asians ◽  
Childhood All ◽  
Genome Wide

Abstract Scrutiny of the human genome through evaluation of common genetic variants has revealed hundreds of disease susceptibility loci. In childhood acute lymphoblastic leukemia (ALL), six regions that have replicated in several populations are now considered known susceptibility loci (ARID5B, IKZF1, CEBPE, CDKN2A, PIP4K2A, and GATA3), but their effects have yet to be fully confirmed in populations of non-European ancestry. Targeted validation attempts based on the same SNPs originally identified in European ancestral populations have been performed in East Asians, but findings have been inconsistent. This may be due to differences in linkage disequilibrium patterns, allele frequency, and/or magnitude of effect between Europeans and East Asians; thus a comprehensive characterization of genetic variation across the targeted genetic loci is required for an appropriate validation attempt in different populations. Using a large network of hospitals within the Tokyo Children's Cancer Study Group, saliva samples from previously diagnosed childhood ALL patients (aged 0-19 years) were collected between December 2012 and May 2015. Genome-wide single nucleotide polymorphism (SNP) genotyping was performed and resulted in the inclusion of a total of 570 ALL patients, with genetic data available for up to about 500,000 SNPs after quality control exclusions. Control genome-wide data were available for 2,712 previously genotyped samples from the Nagahama Study Group and Aichi Cancer Center Study, Japan. SNP imputation was performed on the combined case-control dataset using ShapeIT and Minimac3, and the 1000 Genomes Project Phase I Version 3 as the reference population. Tests of association between childhood ALL and all available SNP genotypes across the six genes (mentioned above) implicated in previous genome-wide association studies was performed using logistic regression and assuming a log-additive model of inheritance. Of the six genomic regions examined, SNPs within the IKZF1, ARID5B, and PIP4K2A genes showed a statistically significant association with childhood ALL risk after Bonferroni correction. SNPs with the strongest evidence of association for these three genes included rs7090445 (ARID5B, OR=1.75, P =3.7x10-17), rs12533431 (IKZF1, OR=1.43, P =4.3x10-5), and rs11013045 (PIP4K2A, OR=0.76, P =9.5x10-5). Further examination of these regions indicated a second independently associated locus within ARID5B. Furthermore, we observed that the same previously reported primary ALL susceptibility SNPs for IKZF1 (e.g. rs4132601, rs11978267) and PIP4K2A (e.g. rs10828317, rs7088318) were not associated in Japanese. This highlights the importance of considering regional genetic variation comprehensively when testing the role of previously implicated candidate regions in a different racial/ethnic population. Characterization of the role of CEBPE, CDKN2A, and GATA3 genetic variation in Japanese may benefit from greater statistical power and potentially additional coverage of SNPs within these regions. Disclosures No relevant conflicts of interest to declare.

scholarly journals Genetics of psoriasis: a basis for precision medicine

2019 ◽  
Vol 2 (2) ◽  
pp. 120-130 ◽  
Author(s):  
Delin Ran ◽  
Minglong Cai ◽  
Xuejun Zhang
Keyword(s):  
Genetic Variation ◽  
Precision Medicine ◽  
Genetic Factors ◽  
Genome Wide Association Study ◽  
Direct Sequencing ◽  
Disease Prediction ◽  
Inflammatory Skin Disease ◽  
Polygenic Inheritance ◽  
Genome Wide

AbstractPsoriasis is an inflammatory skin disease with a background of polygenic inheritance. Both environmental and genetic factors are involved in the etiology of the disease. In the last two decades, numerous studies have been conducted through linkage analysis, genome-wide association study (GWAS), and direct sequencing to explore the role of genetic variation in disease pathogenesis and progression. To date, >80 psoriasis susceptibility genes have been identified, including HLA-Cw6, IL12B, IL23R, and LCE3B/3C. Some genetic markers have been applied in disease prediction, clinical diagnosis, treatment, and new drug development, which could further explain the pathogenesis of psoriasis and promote the development of precision medicine. This review summarizes related research on genetic variation in psoriasis and explores implications of the findings in clinical application and the promotion of a personalized medicine project.

scholarly journals Apolipoprotein B gene polymorphisms and serum lipids: meta-analysis of the role of genetic variation in responsiveness to diet

2000 ◽  
Vol 71 (3) ◽  
pp. 713-724 ◽  
Author(s):  
Maire Rantala ◽  
Tapio T Rantala ◽  
Markku J Savolainen ◽  
Yechiel Friedlander ◽  
Y Antero Kesäniemi
Keyword(s):  
Genetic Variation ◽  
Apolipoprotein B ◽  
Gene Polymorphisms ◽  
Serum Lipids ◽  
Meta Analysis ◽  
Apolipoprotein B Gene

scholarly journals Genome-Wide Association Analyses Identify Variants in IRF4 Associated With Acute Myeloid Leukemia and Myelodysplastic Syndrome Susceptibility

2021 ◽  
Vol 12 ◽  
Author(s):  
Junke Wang ◽  
Alyssa I. Clay-Gilmour ◽  
Ezgi Karaesmen ◽  
Abbas Rizvi ◽  
Qianqian Zhu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Acute Myeloid Leukemia ◽  
Genetic Variation ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Genome Wide Association ◽  
Genome Wide ◽  
Increased Risk ◽  
Acute Myeloid

The role of common genetic variation in susceptibility to acute myeloid leukemia (AML), and myelodysplastic syndrome (MDS), a group of rare clonal hematologic disorders characterized by dysplastic hematopoiesis and high mortality, remains unclear. We performed AML and MDS genome-wide association studies (GWAS) in the DISCOVeRY-BMT cohorts (2,309 cases and 2,814 controls). Association analysis based on subsets (ASSET) was used to conduct a summary statistics SNP-based analysis of MDS and AML subtypes. For each AML and MDS case and control we used PrediXcan to estimate the component of gene expression determined by their genetic profile and correlate this imputed gene expression level with risk of developing disease in a transcriptome-wide association study (TWAS). ASSET identified an increased risk for de novo AML and MDS (OR = 1.38, 95% CI, 1.26-1.51, Pmeta = 2.8 × 10–12) in patients carrying the T allele at s12203592 in Interferon Regulatory Factor 4 (IRF4), a transcription factor which regulates myeloid and lymphoid hematopoietic differentiation. Our TWAS analyses showed increased IRF4 gene expression is associated with increased risk of de novo AML and MDS (OR = 3.90, 95% CI, 2.36-6.44, Pmeta = 1.0 × 10–7). The identification of IRF4 by both GWAS and TWAS contributes valuable insight on the role of genetic variation in AML and MDS susceptibility.

scholarly journals Genome-wide association analyses identify variants in IRF4 associated with acute myeloid leukemia and myelodysplastic syndrome susceptibility

2019 ◽  
Author(s):  
Junke Wang ◽  
Alyssa I. Clay-Gilmour ◽  
Ezgi Karaesmen ◽  
Abbas Rizvi ◽  
Qianqian Zhu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Acute Myeloid Leukemia ◽  
Genetic Variation ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Genome Wide Association ◽  
Genome Wide ◽  
Increased Risk ◽  
Acute Myeloid

ABSTRACTThe role of common genetic variation in susceptibility to acute myeloid leukemia (AML), and myelodysplastic syndrome (MDS), a group of rare clonal hematologic disorders characterized by dysplastic hematopoiesis and high mortality, remains unclear. We performed AML and MDS genome-wide association studies (GWAS) in the DISCOVeRY-BMT cohorts (2309 cases and 2814 controls). Association analysis based on subsets (ASSET) was used to conduct a summary statistics SNP-based analysis of MDS and AML subtypes. For each AML and MDS case and control we used PrediXcan to estimate the component of gene expression determined by their genetic profile and correlate this imputed gene expression level with risk of developing disease in a transcriptome-wide association study (TWAS). ASSET identified an increased risk for de novo AML and MDS (OR=1.38, 95% CI, 1.26-1.51, Pmeta=2.8×10-12) in patients carrying the T allele at rs12203592 in Interferon Regulatory Factor 4 (IRF4), a transcription factor which regulates myeloid and lymphoid hematopoietic differentiation. Our TWAS analyses showed increased IRF4 gene expression is associated with increased risk of de novo AML and MDS (OR=3.90, 95% CI, 2.36-6.44, Pmeta =1.0×10-7). The identification of IRF4 by both GWAS and TWAS contributes valuable insight on the role of genetic variation in AML and MDS susceptibility.

scholarly journals Plastic responses to novel environments are biased towards phenotype dimensions with high additive genetic variation

2019 ◽  
Vol 116 (27) ◽  
pp. 13452-13461 ◽  
Author(s):  
Daniel W. A. Noble ◽  
Reinder Radersma ◽  
Tobias Uller
Keyword(s):  
Genetic Variation ◽  
Meta Analysis ◽  
Additive Genetic Variance ◽  
Genetic Mutation ◽  
Developmental Systems ◽  
Additive Genetic Variation ◽  
Genetic Constraint ◽  
Novel Environments ◽  
Plastic Responses

Environmentally induced phenotypes have been proposed to initiate and bias adaptive evolutionary change toward particular directions. The potential for this to happen depends in part on how well plastic responses are aligned with the additive genetic variance and covariance in traits. Using meta-analysis, we demonstrate that plastic responses to novel environments tend to occur along phenotype dimensions that harbor substantial amounts of additive genetic variation. This suggests that selection for or against environmentally induced phenotypes typically will be effective. One interpretation of the alignment between the direction of plasticity and the main axis of additive genetic variation is that developmental systems tend to respond to environmental novelty as they do to genetic mutation. This makes it challenging to distinguish if the direction of evolution is biased by plasticity or genetic “constraint.” Our results therefore highlight a need for new theoretical and empirical approaches to address the role of plasticity in evolution.

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