Gene by environment interactions

Culverhouse, Robert; Suarez, Brian K.

doi:10.1002/gepi.20282

Cited by 4 publications

(2 citation statements)

References 22 publications

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“…However, there are important power and multiple testing factors to be considered. A 500 K SNP study would result in about 10 11 and 10 16 two and three SNP combinations respectively, and various strategies to improve power and reduce the cost of computation and multiple testing have been published [45][46][47]. But there is no simple method, and the advantages and shortcomings of the analytic strategies should be considered in advance of developing the experimental design of any study of interaction effects.…”

Section: Analysis Issues In Genome-wide Association Studiesmentioning

confidence: 99%

Hypertension and genome-wide association studies: combining high fidelity phenotyping and hypercontrols

Padmanabhan

Melander

Hastie

et al. 2008

Journal of Hypertension

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Among the common complex diseases, hypertension has been particularly unlucky in the recent surge of positive results from genome-wide association studies. We summarize the evidence that would support continuing the effort in the hunt for a genetic basis for hypertension. The problems facing the genetic studies for hypertension are not unique, but phenotypic characterization, heterogeneity and high prevalence make it a special case requiring a more individualized approach. We argue that, even in the presence of a strong environmental component to hypertension risk, the common disease/common variant model is relevant for hypertension and discuss the issues involved in designing a genome-wide association study for hypertension. It is likely that the individual odds ratios for disease variants will be less than 1.3 and, although individually these effect sizes are minor, the combination of even a few such common polymorphisms can have substantial population attributable risks. The identification of hypertension gene variants should provide new insight into the disease susceptibility, progression and severity. This will lead to the identification of potential targets for lifestyle and pharmacological interventions, with the ultimate goal of improving prevention, diagnosis and treatment.

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Section: Analysis Issues In Genome-wide Association Studiesmentioning

confidence: 99%

Hypertension and genome-wide association studies: combining high fidelity phenotyping and hypercontrols

Padmanabhan

Melander

Hastie

et al. 2008

Journal of Hypertension

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“…Identifying gene-environment interactions can further our understanding of the architecture and underlying biology of complex traits. 25 A difference in the effect size of a genetic variant in individuals differing in an environmental or clinical exposure suggests the presence of a gene-environment interaction, rather than simply additive effects of the 2 exposures. 26 Unfortunately, the ability to measure accurately environmental exposures is a limiting factor.…”

Section: Integrative Analyses To Extend Gwas Findingsmentioning

confidence: 99%

2018 George Lyman Duff Memorial Lecture

McPherson

2019

ATVB

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Recent studies have led to a broader understanding of the genetic architecture of coronary artery disease and demonstrate that it largely derives from the cumulative effect of multiple common risk alleles individually of small effect size rather than rare variants with large effects on coronary artery disease risk. The tools applied include genome-wide association studies encompassing over 200 000 individuals complemented by bioinformatic approaches including imputation from whole-genome data sets, expression quantitative trait loci analyses, and interrogation of ENCODE (Encyclopedia of DNA Elements), Roadmap Epigenetic Project, and other data sets. Over 160 genome-wide significant loci associated with coronary artery disease risk have been identified using the genome-wide association studies approach, 90% of which are situated in intergenic regions. Here, I will describe, in part, our research over the last decade performed in collaboration with a series of bright trainees and an extensive number of groups and individuals around the world as it applies to our understanding of the genetic basis of this complex disease. These studies include computational approaches to better understand missing heritability and identify causal pathways, experimental approaches, and progress in understanding at the molecular level the function of the multiple risk loci identified and potential applications of these genomic data in clinical medicine and drug discovery.

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Inhibition of TNF-alpha secretion from peripheral blood monocular cells by triptolid is associated with TNF-alpha-308 gene polymorphisms in rheumatoid arthritis patients

Xiuliang

Xiong

et al. 2010

Front. Med. China

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This study examined the inhibitory effect of triptolid (TP) on tumor necrosis factor-α (TNF-α) secreted from peripheral blood monocular cells (PBMCs) and the association of the inhibitory effect with TNF-α-308 gene polymorphisms in rheumatoid arthritis (RA) patients. Gene polymorphism at A-G site 308 in the promoter region of TNF-α gene was detected in 42 RA patients by using allele specific polymerase chain reaction (AS-PCR) assay. PBMCs were harvested from these patients and treated first with lipopolysaccharides (LPS) and then with different doses of TP (1, 5.4 and 15 ng/mL). The TNF-α level in the supernatants was measured by enzyme-linked immunosorbent assay (ELISA). The results showed that TNF-α level in the supernatants of TP (1 ng/mL)-treated PBMCs was decreased by 3.80% and 4.91%, respectively, in the patients with AA and AG genotypes, when compared with those treated with LPS alone (P > 0.05). Moreover, the TNF-α level in the patients with GG genotype was reduced by 20.74% (P < 0.05). When PBMCs were treated with TP at 5.4 ng/mL, TNF-α levels in the patients with AA, AG, and GG genotypes were decreased by 20.42%, 34.73%, and 41.69%, respectively (P < 0.05). The TNF-α level was slightly higher in the PBMCs treated with 15 ng/mL of TP than those in the two TP groups in the patients carrying AA, AG, and GG genotypes (P > 0.05). It was concluded that gene polymorphism at TNF-α-308 sites may relate to the secretion of TNF-α in RA patients. TP has different inhibitory effects on the secretion of TNF-α in the patients harboring different genotypes, which may be one of the reasons for individual variation in response to TP.

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Gene by environment interactions

Cited by 4 publications

References 22 publications

Hypertension and genome-wide association studies: combining high fidelity phenotyping and hypercontrols

Hypertension and genome-wide association studies: combining high fidelity phenotyping and hypercontrols

2018 George Lyman Duff Memorial Lecture

Inhibition of TNF-alpha secretion from peripheral blood monocular cells by triptolid is associated with TNF-alpha-308 gene polymorphisms in rheumatoid arthritis patients

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