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Association Genetics Identifies Single Nucleotide Polymorphisms Related to Kernel Oil Content and Quality in Camellia oleifera.
Lin, P, Yin, H, Yan, C, Yao, X, Wang, K
Journal of agricultural and food chemistry. 2019;(9):2547-2562
Abstract
Camellia oleifera, as an important nonwood tree species for seed oil in China, has received enormous attention owing to its high unsaturated fatty acid contents benefited to human health. It is necessary to examine allelic diversity of key genes that are associated with oil production in C. oleifera cultivars with a large variation of fatty acid compositions. In this study, we performed the association analysis between four key genes (two CoSAD and two Cofad2) coding fatty acid desaturases and traits including oil content and fatty acid composition. We identified two single nucleotide insertion-deletion (InDel) and 362 single-nucleotide polymorphisms (SNPs) within the four candidate genes by sequencing an association population (216 accessions). Single-marker (or haplotype) and traits association tests were conducted by linkage disequilibrium (LD) approaches to detect significant marker-trait associations. Validation population (279 hybrid individuals from six full-sibs families) studies were performed to validate the function of allelic variations significantly associated. In all, 90 single marker-trait and one haplotype-trait associations were significant in association population, and these loci explained 1.87-17.93% proportion of the corresponding phenotypic variance. Further, six SNP marker-trait associations ( Q < 0.10) from Cofad2-A, CoSAD1, and CoSAD2 were successfully validated in the validation population. The SNP markers identified in this study can potentially be applied for future marker-assisted selection to improve oil content and quality in C. oleifera.
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Association between oral cleft and transcobalamin 2 polymorphism in a sample study from Nassiriya, Iraq.
Carinci, F, Palmieri, A, Scapoli, L, Cura, F, Abenavoli, F, Giannì, AB, Russillo, A, Docimo, R, Martinelli, M
International journal of immunopathology and pharmacology. 2019;:2058738419855571
Abstract
Orofacial clefts are common congenital defects whose prevalence differs between geographical regions and ethnic groups. The inheritance is complex, involving the contribution of both genetic and environmental factors. The involvement of genes belonging to the folate pathway is still matter of debate, with strong evidences of association and conflicting results. After demonstrating the contribution, for a sample from the Italian population, of common mutations mapping on three genes of the folate pathway, our group tried to unravel their contribution in independent sample studies with different ethnicity. In the present investigation a set of 34 triads with oral cleft from Nassiriya, Iraq, has been genotyped for rs1801133 of MTHFR, rs1801198 of TCN2, and rs4920037 of CBS polymorphisms. Association analysis evidenced a decreased risk of cleft for children carrying the 667G allele at TCN2 gene (P = 0.02). This evidence further supported the relationship between polymorphisms of folate related genes and oral clefts, and outlined the relevance of studying populations having different ethnicity.
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BMI-associated gene variants in FTO and cardiometabolic and brain disease: obesity or pleiotropy?
Ganeff, IMM, Bos, MM, van Heemst, D, Noordam, R
Physiological genomics. 2019;(8):311-322
Abstract
Obesity is a causal risk factor for the development of age-related disease conditions, which includes Type 2 diabetes mellitus, cardiovascular disease, and dementia. In genome-wide association studies, genetic variation in FTO is strongly associated with obesity and has been described across different ethnic backgrounds and life stages. To date, much work has been devoted on determining the biological mechanisms via which FTO affects body weight regulation and ultimately contributes to age-related cardiometabolic and brain disease. The main hypotheses of the involved biological mechanisms include the involvement of FTO in habitual food intake and energy expenditure. In this narrative review, our overall aim is to provide an overview on how FTO gene variants could increase the risk of developing age-related disease conditions. Specifically, we will discuss the state of the literature based on the different hypotheses how FTO regulates body weight and ultimately contributes to cardiometabolic disease and brain disease.
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Contribution of MTR A2756G polymorphism and MTRR A66G polymorphism to the risk of idiopathic male infertility.
Ren, ZJ, Zhang, YP, Ren, PW, Yang, B, Deng, S, Peng, ZF, Liu, LR, Wei, W, Dong, Q
Medicine. 2019;(51):e18273
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Abstract
BACKGROUND Methionine synthase reductase gene (MTRR A66G) polymorphism and methionine synthase gene (MTR A2756G) polymorphism have shown an association with idiopathic male infertility risk in several ethnic populations. However, their small sample sizes and inconsistent outcomes have prevented strong conclusions. We performed a meta-analysis with published studies to evaluate the associations of the 2 single nucleotide polymorphisms (SNPs) and idiopathic male infertility risk. METHODS A thorough literature search was performed up to Jun 21, 2019 with Medline, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), China Biology Medical literature (CBM), China Science and Technology Journal Database (VIP), and Chinese literature (Wan Fang) databases. Odds ratio (OR) and 95% confidence interval (95% CI) were used to assess the strength of associations. RESULTS Seventeen studies including 3269 cases and 3192 controls met the inclusion criteria. Our meta-analysis showed that the MTR A2756G mutation may contribute to genetic susceptibility to the risk of idiopathic male infertility in Non-Asians, but not to Asian population, whereas the MTRR A66G polymorphism may be unrelated to idiopathic male infertility in both Non-Asian and Asian populations. In the stratified analysis by infertility type, the MTR A2756G polymorphism was a risk factor for both non-obstructive azoospermia (NOA) and oligoasthenoteratozoospermia (OAT) patients. However, the MTRR A66G polymorphism is associated with risk for OAT in Asian, but not in Non-Asian population. CONCLUSION This meta-analysis suggested that the MTR A2756G and MTRR A66G polymorphisms were risk factors for idiopathic male infertility. Studies with larger sample sizes and representative population-based cases and well-matched controls are needed to validate our results.
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The effects of genetic variants related to insulin metabolism pathways and the interactions with lifestyles on colorectal cancer risk.
Jung, SY, Zhang, ZF
Menopause (New York, N.Y.). 2019;(7):771-780
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OBJECTIVES Genetic variants in metabolic signaling pathways may interact with lifestyle factors, such as dietary fatty acids, influencing postmenopausal colorectal cancer (CRC) risk, but these interrelated pathways are not fully understood. METHODS In this study, we examined 54 single-nucleotide polymorphisms (SNPs) in genes related to insulin-like growth factor-I/insulin traits and their signaling pathways and lifestyle factors in relation to postmenopausal CRC, using data from 6,539 postmenopausal women in the Women's Health Initiative Harmonized and Imputed Genome-Wide Association Studies. By employing a two-stage random survival forest analysis, we evaluated the SNPs and lifestyle factors by ranking them according to their predictive value and accuracy for CRC. RESULTS We identified four SNPs (IRS1 rs1801123, IRS1 rs1801278, AKT2 rs3730256, and AKT2 rs7247515) and two lifestyle factors (age and percentage calories from saturated fatty acids) as the top six most influential predictors for CRC risk. We further examined interactive effects of those factors on cancer risk. In the individual SNP analysis, no significant association was observed, but the combination of the four SNPs, age, and percentage calories from saturated fatty acid (≥11% per day) significantly increased the risk of CRC in a gene and lifestyle dose-dependent manner. CONCLUSIONS Our findings provide insight into gene-lifestyle interactions and will enable researchers to focus on individuals with risk genotypes to promote intervention strategies. Our study suggests the careful use of data on potential genetic targets in clinical trials for cancer prevention to reduce the risk for CRC in postmenopausal women.
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Discovery of the first genome-wide significant risk loci for attention deficit/hyperactivity disorder.
Demontis, D, Walters, RK, Martin, J, Mattheisen, M, Als, TD, Agerbo, E, Baldursson, G, Belliveau, R, Bybjerg-Grauholm, J, Bækvad-Hansen, M, et al
Nature genetics. 2019;(1):63-75
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Attention deficit/hyperactivity disorder (ADHD) is a highly heritable childhood behavioral disorder affecting 5% of children and 2.5% of adults. Common genetic variants contribute substantially to ADHD susceptibility, but no variants have been robustly associated with ADHD. We report a genome-wide association meta-analysis of 20,183 individuals diagnosed with ADHD and 35,191 controls that identifies variants surpassing genome-wide significance in 12 independent loci, finding important new information about the underlying biology of ADHD. Associations are enriched in evolutionarily constrained genomic regions and loss-of-function intolerant genes and around brain-expressed regulatory marks. Analyses of three replication studies: a cohort of individuals diagnosed with ADHD, a self-reported ADHD sample and a meta-analysis of quantitative measures of ADHD symptoms in the population, support these findings while highlighting study-specific differences on genetic overlap with educational attainment. Strong concordance with GWAS of quantitative population measures of ADHD symptoms supports that clinical diagnosis of ADHD is an extreme expression of continuous heritable traits.
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PPARG and FTO polymorphism can modulate the outcomes of a central European diet and a Mediterranean diet in centrally obese postmenopausal women.
Chmurzynska, A, Muzsik, A, Krzyżanowska-Jankowska, P, Mądry, E, Walkowiak, J, Bajerska, J
Nutrition research (New York, N.Y.). 2019;:94-100
Abstract
The aim of this study was to test the hypothesis that polymorphism of genes with the biggest effects on body mass (FTO and PPARG) can affect the results of dieting in centrally obese postmenopausal women. A total of 144 volunteers were randomized to a 16-week intervention with two hypocaloric diets: either a Mediterranean diet (MED) moderate in fat (37% total energy as fat) or the Central European diet (CED) moderate in carbohydrates (55% total energy as carbohydrates). The associations between FTO and PPARG polymorphism on the baseline body mass, body composition, blood pressure, lipid and non-lipid parameters, and their changes after the trial were analyzed. None of the examined baseline outcomes differed in the rs9939609 FTO subgroups; abdominal fat was higher in the minor (G) allele carriers of the PPARG rs1801282. After the intervention, in the CED group, the PPARG G allele carriers showed greater reductions in weight (-6.58 ± 0.61 vs -9.58 ± 0.83; P < .01), lean mass (-0.38 ± 0.29 vs -1.79 ± 0.38; P < .05) and high-density lipoprotein (HDL) cholesterol (-0.46 ± 0.77 vs -5.25 ± 1.49; P < .01) than the CC homozygotes, and the TT individuals of the rs9939609 FTO had greater reductions in diastolic blood pressure (-9.03 ± 1.78 vs. -7.58 ± 1.50; P < .05). In the MED group, greater reductions in abdominal fat were observed in the G allele carriers than in the CC homozygotes (-3.31 ± 0.26 vs. -4.23 ± 0.41; P < .05). PPARG and FTO polymorphism may affect the outcomes of the diets aimed at weight reduction in postmenopausal women.
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Genome-wide meta-analysis of SNP-by9-ACEI/ARB and SNP-by-thiazide diuretic and effect on serum potassium in cohorts of European and African ancestry.
Irvin, MR, Sitlani, CM, Noordam, R, Avery, CL, Bis, JC, Floyd, JS, Li, J, Limdi, NA, Srinivasasainagendra, V, Stewart, J, et al
The pharmacogenomics journal. 2019;(1):97-108
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We evaluated interactions of SNP-by-ACE-I/ARB and SNP-by-TD on serum potassium (K+) among users of antihypertensive treatments (anti-HTN). Our study included seven European-ancestry (EA) (N = 4835) and four African-ancestry (AA) cohorts (N = 2016). We performed race-stratified, fixed-effect, inverse-variance-weighted meta-analyses of 2.5 million SNP-by-drug interaction estimates; race-combined meta-analysis; and trans-ethnic fine-mapping. Among EAs, we identified 11 significant SNPs (P < 5 × 10-8) for SNP-ACE-I/ARB interactions on serum K+ that were located between NR2F1-AS1 and ARRDC3-AS1 on chromosome 5 (top SNP rs6878413 P = 1.7 × 10-8; ratio of serum K+ in ACE-I/ARB exposed compared to unexposed is 1.0476, 1.0280, 1.0088 for the TT, AT, and AA genotypes, respectively). Trans-ethnic fine mapping identified the same group of SNPs on chromosome 5 as genome-wide significant for the ACE-I/ARB analysis. In conclusion, SNP-by-ACE-I /ARB interaction analyses uncovered loci that, if replicated, could have future implications for the prevention of arrhythmias due to anti-HTN treatment-related hyperkalemia. Before these loci can be identified as clinically relevant, future validation studies of equal or greater size in comparison to our discovery effort are needed.
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Genome-wide association analysis of common genetic variants of resistant hypertension.
El Rouby, N, McDonough, CW, Gong, Y, McClure, LA, Mitchell, BD, Horenstein, RB, Talbert, RL, Crawford, DC, , , Gitzendanner, MA, et al
The pharmacogenomics journal. 2019;(3):295-304
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Resistant hypertension (RHTN), defined as uncontrolled blood pressure (BP) ≥ 140/90 using three or more drugs or controlled BP (<140/90) using four or more drugs, is associated with adverse outcomes, including decline in kidney function. We conducted a genome-wide association analysis in 1194 White and Hispanic participants with hypertension and coronary artery disease from the INternational VErapamil-SR Trandolapril STudy-GENEtic Substudy (INVEST-GENES). Top variants associated with RHTN at p < 10-4 were tested for replication in 585 White and Hispanic participants with hypertension and subcortical strokes from the Secondary Prevention of Subcortical Strokes GENEtic Substudy (SPS3-GENES). A genetic risk score for RHTN was created by summing the risk alleles of replicated RHTN signals. rs11749255 in MSX2 was associated with RHTN in INVEST (odds ratio (OR) (95% CI) = 1.50 (1.2-1.8), p = 7.3 × 10-5) and replicated in SPS3 (OR = 2.0 (1.4-2.8), p = 4.3 × 10-5), with genome-wide significance in meta-analysis (OR = 1.60 (1.3-1.9), p = 3.8 × 10-8). Other replicated signals were in IFLTD1 and PTPRD. IFLTD1 rs6487504 was associated with RHTN in INVEST (OR = 1.90 (1.4-2.5), p = 1.1 × 10-5) and SPS3 (OR = 1.70 (1.2-2.5), p = 4 × 10-3). PTPRD rs324498, a previously reported RHTN signal, was among the top signals in INVEST (OR = 1.60 (1.3-2.0), p = 3.4 × 10-5) and replicated in SPS3 (OR = 1.60 (1.1-2.4), one-sided p = 0.005). Participants with the highest number of risk alleles were at increased risk of RHTN compared to participants with a lower number (p-trend = 1.8 × 10-15). Overall, we identified and replicated associations with RHTN in the MSX2, IFLTD1, and PTPRD regions, and combined these associations to create a genetic risk score.
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Single nucleotide polymorphisms at the ADIPOQ gene locus rs1501299 interact with different type of dietary fatty acids in two hypocaloric diets.
de Luis, DA, Izaola, O, Primo, D, Aller, R
European review for medical and pharmacological sciences. 2019;(7):2960-2970
Abstract
OBJECTIVE Some adiponectin gene (ADIPOQ) and single nucleotide polymorphisms (SNPs) have been related to adiponectin levels and metabolic parameters. Few studies of interaction gene-nutrient have been realized in this topic area. The aim of our study was to analyze the effect of the rs1501299 ADIPOQ gene polymorphism, and the dietary intake on total adiponectin levels and the insulin resistance changes after an enriched-monounsaturated fat (Diet M) vs. an enriched-polyunsaturated fat hypocaloric diet (Diet P). PATIENTS AND METHODS A Caucasian population of 363 obese patients was enrolled in a randomized clinical trial with two hypocaloric diets. Before and after 12 weeks on each hypocaloric diet, an anthropometric evaluation, an assessment of nutritional intake and a biochemical analysis were realized. The statistical analysis was performed for the combined GT and TT as a group (mutant) and GG as second group (wild). RESULTS With both caloric restriction strategies, body weight, body mass index (BMI), fat mass, waist circumference, systolic blood pressure and leptin levels decreased. After Diet P, only subjects with GG genotype showed a significant improvement in the insulin levels (GG vs. GT±TT) (-3.2±1.0 mU/L vs. -0.6±0.4 mU/L: p=0.01) and in the homeostasis model assessment (HOMA-IR) (-1.1±0.2 units vs. -0.3±0.4 units: p=0.02). The same improvement in both parameters was reported after Diet M: insulin levels (-3.7±0.9 mU/L vs. -0.4±0.5 mU/L: p=0.01) and HOMA-IR (-1.0±0.2 units vs. -0.4±0.3 units: p=0.03). After weight loss with diet M, both genotypes (GG vs. GT±TT) showed similar decrease in total cholesterol and LDL-cholesterol. Only subjects with GG genotype showed a significant increase of the adiponectin levels after both diets: (Diet P: 9.3±3.0 ng/dl vs. Diet M: 8.2±2.9 ng/dl: p=0.38). CONCLUSIONS The GG genotype of ADIPOQ gene variant (rs1501299) is associated to a significant improvement in the adiponectin levels and a decrease of insulin and HOMA-IR after two different hypocaloric diets with different profile of unsaturated dietary fats.