Lifestyle Genomics最新文献

{"title":"Smoking-Interaction Loci Affect Obesity Traits: A Gene-Smoking Stratified Meta-Analysis of 545,131 Europeans.","authors":"Won-Jun Lee, Ji Eun Lim, Ji-One Kang, Tae-Woong Ha, Hae-Un Jung, Dong Jun Kim, Eun Ju Baek, Han Kyul Kim, Ju Yeon Chung, Bermseok Oh","doi":"10.1159/000525749","DOIUrl":"10.1159/000525749","url":null,"abstract":"<p><strong>Introduction: </strong>Although many studies have investigated the association between smoking and obesity, very few have analyzed how obesity traits are affected by interactions between genetic factors and smoking. Here, we aimed to identify the loci that affect obesity traits via smoking status-related interactions in European samples.</p><p><strong>Methods: </strong>We performed stratified analysis based on the smoking status using both the UK Biobank (UKB) data (N = 334,808) and the Genetic Investigation of ANthropometric Traits (GIANT) data (N = 210,323) to identify gene-smoking interaction for obesity traits. We divided the UKB subjects into two groups, current smokers and nonsmokers, based on the smoking status, and performed genome-wide association study (GWAS) for body mass index (BMI), waist circumference adjusted for BMI (WCadjBMI), and waist-hip ratio adjusted for BMI (WHRadjBMI) in each group. And then we carried out the meta-analysis using both GWAS summary statistics of UKB and GIANT for BMI, WCadjBMI, and WHRadjBMI and computed the stratified p values (pstratified) based on the differences between meta-analyzed estimated beta coefficients with standard errors in each group.</p><p><strong>Results: </strong>We identified four genome-wide significant loci in interactions with the smoking status (pstratified < 5 × 10-8): rs336396 (INPP4B) and rs12899135 (near CHRNB4) for BMI, and rs998584 (near VEGFA) and rs6916318 (near RSPO3) for WHRadjBMI. Moreover, we annotated the biological functions of the SNPs using expression quantitative trait loci (eQTL) and GWAS databases, along with publications, which revealed possible mechanisms underlying the association between the smoking status-related genetic variants and obesity.</p><p><strong>Conclusions: </strong>Our findings suggest that obesity traits can be modified by the smoking status via interactions with genetic variants through various biological pathways.</p>","PeriodicalId":18030,"journal":{"name":"Lifestyle Genomics","volume":"15 3","pages":"87-97"},"PeriodicalIF":2.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9905158","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quantile-Specific Heritability of Mean Platelet Volume, Leukocyte Count, and Other Blood Cell Phenotypes.","authors":"Paul T Williams","doi":"10.1159/000527048","DOIUrl":"https://doi.org/10.1159/000527048","url":null,"abstract":"<p><strong>Introduction: </strong>\"Quantile-dependent expressivity\" occurs when the effect size of a genetic variant depends upon whether the phenotype (e.g., mean platelet volume, MPV) is high or low relative to its distribution.</p><p><strong>Methods: </strong>Offspring-parent regression slopes (βOP) were estimated by quantile regression, from which quantile-specific heritabilities (h2) were calculated (h2 = 2βOP/[1 + rspouse]) for blood cell phenotypes in 3,929 parent-offspring pairs from the Framingham Heart Study.</p><p><strong>Results: </strong>Quantile-specific h2 (±SE) increased with increasing percentiles of the offspring's age- and sex-adjusted MPV distribution (plinear = 0.0001): 0.48 ± 0.09 at the 10th, 0.53 ± 0.04 at the 25th, 0.70 ± 0.06 at the 50th, 0.74 ± 0.06 at the 75th, and 0.90 ± 0.12 at the 90th percentile. Quantile-specific h2 also increased with increasing percentiles of the offspring's white blood cell (WBC, plinear = 0.002), monocyte (plinear = 0.01), and eosinophil distributions (plinear = 0.0005). In contrast, heritibilities of red blood cell (RBC) count, hematocrit (HCT), and hemoglobin (HGB) showed little evidence of quantile dependence. Quantile-dependent expressivity is consistent with gene-environment interactions reported by others, including (1) greater increases in WBC and PLT concentrations in subjects who are glutathione-S-transferase Mu1 (GSTM1) null homozygotes than GSTM1 sufficient when exposed to endotoxin; (2) significantly higher WBC count in AA homozygotes than carriers of the G-allele of the glutathione S-transferase P1 (GSTP1) rs1695 polymorphism at low but not high benzene exposure in shoe factory workers; (3) higher WBC counts in TT homozygotes than C-allele carriers of the interleukin-1β (IL1B) c.315C>T polymorphism after undergoing surgery for infective endocarditis but not before surgery.</p><p><strong>Discussion/conclusion: </strong>Quantile-dependent expressivity may explain several purported gene-environment interactions involving blood cell phenotypes.</p>","PeriodicalId":18030,"journal":{"name":"Lifestyle Genomics","volume":"15 4","pages":"111-123"},"PeriodicalIF":2.6,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10511418","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"APOE Genotypes, Lipid Profiles, and Associated Clinical Markers in a Finnish Population with Cardiovascular Disease Risk Factors.","authors":"Heidi Leskinen,&nbsp;Maaria Tringham,&nbsp;Heli Karjalainen,&nbsp;Terhi Iso-Touru,&nbsp;Hanna-Leena Hietaranta-Luoma,&nbsp;Pertti Marnila,&nbsp;Juha-Matti Pihlava,&nbsp;Timo Hurme,&nbsp;Hannu Puolijoki,&nbsp;Kari Åkerman,&nbsp;Sari Mäkinen,&nbsp;Mari Sandell,&nbsp;Kirsi Vähäkangas,&nbsp;Raija Tahvonen,&nbsp;Susanna Rokka,&nbsp;Anu Hopia","doi":"10.1159/000520864","DOIUrl":"https://doi.org/10.1159/000520864","url":null,"abstract":"<p><strong>Introduction: </strong>The APOE ε4 allele predisposes to high cholesterol and increases the risk for lifestyle-related diseases such as Alzheimer's disease and cardiovascular diseases (CVDs). The aim of this study was to analyse interrelationships of APOE genotypes with lipid metabolism and lifestyle factors in middle-aged Finns among whom the CVD risk factors are common.</p><p><strong>Methods: </strong>Participants (n = 211) were analysed for APOE ε genotypes, physiological parameters, and health- and diet-related plasma markers. Lifestyle choices were determined by a questionnaire.</p><p><strong>Results: </strong>APOE genotypes ε3/ε4 and ε4/ε4 (ε4 group) represented 34.1% of the participants. Genotype ε3/ε3 (ε3 group) frequency was 54.5%. Carriers of ε2 (ε2 group; ε2/ε2, ε2/ε3 and ε2/ε4) represented 11.4%; 1.9% were of the genotype ε2/ε4. LDL and total cholesterol levels were lower (p < 0.05) in the ε2 carriers than in the ε3 or ε4 groups, while the ε3 and ε4 groups did not differ. Proportions of plasma saturated fatty acids (SFAs) were higher (p < 0.01), and omega-6 fatty acids lower (p = 0.01) in the ε2 carriers compared with the ε4 group. The ε2 carriers had a higher (p < 0.05) percentage of 22:4n-6 and 22:5n-6 and a lower (p < 0.05) percentage of 24:5n-3 and 24:6n-3 than individuals without the ε2 allele.</p><p><strong>Conclusions: </strong>The plasma fatty-acid profiles in the ε2 group were characterized by higher SFA and lower omega-6 fatty-acid proportions. Their lower cholesterol values indicated a lower risk for CVD compared with the ε4 group. A novel finding was that the ε2 carriers had different proportions of 22:4n-6, 22:5n-6, 24:5n-3, and 24:6n-3 than individuals without the ε2 allele. The significance of the differences in fatty-acid composition remains to be studied.</p>","PeriodicalId":18030,"journal":{"name":"Lifestyle Genomics","volume":"15 2","pages":"45-54"},"PeriodicalIF":2.6,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39751573","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Applications of Metabolomics to Precision Nutrition.","authors":"Marcia LeVatte,&nbsp;Ammar Hassanzadeh Keshteli,&nbsp;Parvin Zarei,&nbsp;David S Wishart","doi":"10.1159/000518489","DOIUrl":"https://doi.org/10.1159/000518489","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;For thousands of years, disabilities due to nutrient deficiencies have plagued humanity. Rickets, scurvy, anemia, stunted growth, blindness, and mental handicaps due to nutrient deficiencies affected up to 1/10 of the world's population prior to 1900. The discovery of essential amino acids, vitamins, and minerals, in the early 1900s, led to a fundamental change in our understanding of food and a revolution in human health. Widespread vitamin and mineral supplementation, the development of recommended dietary allowances, and the implementation of food labeling and testing along with significant improvements in food production and food quality have meant that nutrient-related disorders have almost vanished in the developed world. The success of nutritional science in preventing disease at a population-wide level is one of the great scientific triumphs of the 20th century. The challenge for nutritional science in the 21st century is to understand how to use nutrients and other food constituents to enhance human health or prevent disease at a more personal level. This is the primary goal of precision nutrition.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Summary: &lt;/strong&gt;Precision nutrition is an emerging branch of nutrition science that aims to use modern omics technologies (genomics, proteomics, and metabolomics) to assess an individual's response to specific foods or dietary patterns and thereby determine the most effective diet or lifestyle interventions to prevent or treat specific diseases in that individual. Metabolomics is vital to nearly every aspect of precision nutrition. It can be used to comprehensively characterize the thousands of chemicals in foods, to identify food byproducts in human biofluids or tissues, to characterize nutrient deficiencies or excesses, to monitor biochemical responses to dietary interventions, to track long-term or short-term dietary habits, and to guide the development of nutritional therapies. In this review, we will describe how metabolomics has been used to advance the field of precision nutrition by providing some notable examples or use cases. First, we will describe how metabolomics helped launch the field of precision nutrition through the diagnosis and dietary therapy of individuals with inborn errors of metabolism. Next, we will describe how metabolomics is being used to comprehensively characterize the full chemical complexity of many key foods, and how this is revealing much more about nutrients than ever imagined. Third, we will describe how metabolomics is being used to identify food consumption biomarkers and how this opens the door to a more objective and quantitative assessments of an individual's diet and their response to certain foods. Finally, we will describe how metabolomics is being coupled with other omics technologies to develop custom diets and lifestyle interventions that are leading to positive health benefits. Key Message: Metabolomics is vital to the advancement of nutritional sc","PeriodicalId":18030,"journal":{"name":"Lifestyle Genomics","volume":" ","pages":"1-9"},"PeriodicalIF":2.6,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39414674","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quantile-Dependent Heritability of Glucose, Insulin, Proinsulin, Insulin Resistance, and Glycated Hemoglobin.","authors":"Paul T Williams","doi":"10.1159/000519382","DOIUrl":"10.1159/000519382","url":null,"abstract":"<p><strong>Background: </strong>\"Quantile-dependent expressivity\" is a dependence of genetic effects on whether the phenotype (e.g., insulin resistance) is high or low relative to its distribution.</p><p><strong>Methods: </strong>Quantile-specific offspring-parent regression slopes (βOP) were estimated by quantile regression for fasting glucose concentrations in 6,453 offspring-parent pairs from the Framingham Heart Study.</p><p><strong>Results: </strong>Quantile-specific heritability (h2), estimated by 2βOP/(1 + rspouse), increased 0.0045 ± 0.0007 (p = 8.8 × 10-14) for each 1% increment in the fasting glucose distribution, that is, h2 ± SE were 0.057 ± 0.021, 0.095 ± 0.024, 0.146 ± 0.019, 0.293 ± 0.038, and 0.456 ± 0.061 at the 10th, 25th, 50th, 75th, and 90th percentiles of the fasting glucose distribution, respectively. Significant increases in quantile-specific heritability were also suggested for fasting insulin (p = 1.2 × 10-6), homeostatic model assessment of insulin resistance (HOMA-IR, p = 5.3 × 10-5), insulin/glucose ratio (p = 3.9 × 10-5), proinsulin (p = 1.4 × 10-6), proinsulin/insulin ratio (p = 2.7 × 10-5), and glucose concentrations during a glucose tolerance test (p = 0.001), and their logarithmically transformed values.</p><p><strong>Discussion/conclusion: </strong>These findings suggest alternative interpretations to precision medicine and gene-environment interactions, including alternative interpretation of reported synergisms between ACE, ADRB3, PPAR-γ2, and TNF-α polymorphisms and being born small for gestational age on adult insulin resistance (fetal origin theory), and gene-adiposity (APOE, ENPP1, GCKR, IGF2BP2, IL-6, IRS-1, KIAA0280, LEPR, MFHAS1, RETN, TCF7L2), gene-exercise (INS), gene-diet (ACSL1, ELOVL6, IRS-1, PLIN, S100A9), and gene-socioeconomic interactions.</p>","PeriodicalId":18030,"journal":{"name":"Lifestyle Genomics","volume":"15 1","pages":"10-34"},"PeriodicalIF":2.6,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8766916/pdf/nihms-1746619.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10449465","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Upregulated miR-146a Expression in Peripheral Blood Relates to Th17 and Treg Imbalance in Elder Rheumatoid Arthritis Patients.","authors":"Menglan Liu,&nbsp;Tianli Ren,&nbsp;Zhi Lin,&nbsp;Minhui Hua","doi":"10.1159/000525112","DOIUrl":"https://doi.org/10.1159/000525112","url":null,"abstract":"<p><strong>Background: </strong>The expression level of microRNA-146a (miR-146a) increased in peripheral blood and synovialis tissue of rheumatoid arthritis (RA) patient, and it may play an important role in the pathological process of RA. We investigated its possibility as a diagnostic marker and the correlation with T helper 17 (Th17) and Treg cells in elder RA patients.</p><p><strong>Methods: </strong>Blood samples were collected from 38 active RA patients, 38 inactive RA patients, and 40 healthy controls. RNA expression levels of miR-146a were detected from the peripheral blood samples. The proportion of Th17 and Treg cells were analyzed, as well as their cell-specific transcription factor retinoic acid-related orphan receptor variant 2 (RORc) and forkhead box protein 3 (FOXP3). Furthermore, secretion of pre-inflammatory and anti-inflammatory factors was detected. Correlations between miR-146a and these factors were also analyzed.</p><p><strong>Results: </strong>Compared with healthy control, expression levels of miR-146a in inactive and active groups were significantly higher, with the highest level in active group. The expression of miR-146a and the RA severity, Th17 cell ratio, RORc expression, IL-17 level showed a significant positive correlation, while it showed a significantly negative correlation with Treg cell ration, FOXP3 expression, and TGF-β1 secretion.</p><p><strong>Conclusions: </strong>These results suggested that miR-146a may be used as a disease progression marker in the peripheral blood of elder RA patients.</p>","PeriodicalId":18030,"journal":{"name":"Lifestyle Genomics","volume":" ","pages":"98-106"},"PeriodicalIF":2.6,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40402736","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acknowledgement to Reviewers","authors":"","doi":"10.1159/000521289","DOIUrl":"https://doi.org/10.1159/000521289","url":null,"abstract":"","PeriodicalId":18030,"journal":{"name":"Lifestyle Genomics","volume":"14 1","pages":"153 - 153"},"PeriodicalIF":2.6,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44807386","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Erratum","authors":"","doi":"10.1159/000512164","DOIUrl":"https://doi.org/10.1159/000512164","url":null,"abstract":"","PeriodicalId":18030,"journal":{"name":"Lifestyle Genomics","volume":"14 1","pages":"62 - 62"},"PeriodicalIF":2.6,"publicationDate":"2021-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000512164","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45816331","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proceedings of the 4th European Summer School on Nutrigenomics (ESSN 2021), June 21-25, 2021.","authors":"","doi":"10.1159/000517609","DOIUrl":"https://doi.org/10.1159/000517609","url":null,"abstract":"","PeriodicalId":18030,"journal":{"name":"Lifestyle Genomics","volume":"14 3","pages":"91-116"},"PeriodicalIF":2.6,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000517609","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39119288","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gene-Centric Database Reveals Environmental and Lifestyle Relationships for Potential Risk Modification and Prevention.","authors":"Ron L Martin","doi":"10.1159/000512690","DOIUrl":"https://doi.org/10.1159/000512690","url":null,"abstract":"<p><p>The database at Nutrigenetics.net has been under development since 2007 to facilitate the identification and classification of PubMed articles relevant to human genetics. A controlled vocabulary (i.e., standardized terminology) is used to index these records, with links back to PubMed for every article title. This enables the display of indexes (alphabetical subtopic listings) for any given topic, or for any given combination of topics, including for genes and specific genetic variants. Stepwise use of such indexes (first for one topic, then for combinations of topics) can reveal relationships that are otherwise easily overlooked. These relationships include environmental and lifestyle variables with potential relevance to risk modification (both beneficial and detrimental), and to prevention, or at least to the potential delay of symptom onset for health conditions like Alzheimer disease among many others. Thirty-four specific genetic variants have each been mentioned in at least ≥1,000 PubMed titles/abstracts, and these numbers are steadily increasing. The benefits of indexing with standardized terminology are illustrated for genetic variants like MTHFR 677C-T and its various synonyms (e.g., rs1801133 or Ala222Val). Such use of a controlled vocabulary is also helpful for numerous health conditions, and for potential risk modifiers (i.e., potential risk/effect modifiers).</p>","PeriodicalId":18030,"journal":{"name":"Lifestyle Genomics","volume":"14 1","pages":"30-36"},"PeriodicalIF":2.6,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000512690","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38831667","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}