The Experts below are selected from a list of 27282 Experts worldwide ranked by ideXlab platform
L Meng - One of the best experts on this subject based on the ideXlab platform.
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isolation and characterization of polymorphic microsatellite loci from an est library of turbot scophthalmus maximus and cross species amplification
Molecular Ecology Notes, 2007Co-Authors: Songlin Chen, Y Jiang, Xiaolin Liao, L MengAbstract:In the present study, we report 12 polymorphic microsatellite loci developed from a cDNA library from the turbot, Scophthalmus maximus. Observed and expected heterozygosities varied from 0.20 to 1.00 and from 0.18 to 0.78, respectively. No significant linkage disequilibrium between pairs of loci was found, but two loci significantly deviated from Hardy–Weinberg equilibrium after Bonferroni Correction. Cross-species amplifications of these microsatellites in five additional fish species revealed between five and 11 positive amplifications and between zero and four polymorphic loci per species.
Yuanming Zhang - One of the best experts on this subject based on the ideXlab platform.
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improving power and accuracy of genome wide association studies via a multi locus mixed linear model methodology
Scientific Reports, 2016Co-Authors: Shibo Wang, Jianying Feng, Wenlong Ren, Bo Huang, Ling Zhou, Yangjun Wen, Jin Zhang, Jim M Dunwell, Yuanming ZhangAbstract:Genome-wide association studies (GWAS) have been widely used in genetic dissection of complex traits. However, common methods are all based on a fixed-SNP-effect mixed linear model (MLM) and single marker analysis, such as efficient mixed model analysis (EMMA). These methods require Bonferroni Correction for multiple tests, which often is too conservative when the number of markers is extremely large. To address this concern, we proposed a random-SNP-effect MLM (RMLM) and a multi-locus RMLM (MRMLM) for GWAS. The RMLM simply treats the SNP-effect as random, but it allows a modified Bonferroni Correction to be used to calculate the threshold p value for significance tests. The MRMLM is a multi-locus model including markers selected from the RMLM method with a less stringent selection criterion. Due to the multi-locus nature, no multiple test Correction is needed. Simulation studies show that the MRMLM is more powerful in QTN detection and more accurate in QTN effect estimation than the RMLM, which in turn is more powerful and accurate than the EMMA. To demonstrate the new methods, we analyzed six flowering time related traits in Arabidopsis thaliana and detected more genes than previous reported using the EMMA. Therefore, the MRMLM provides an alternative for multi-locus GWAS.
Atul J Butte - One of the best experts on this subject based on the ideXlab platform.
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systematic identification of interaction effects between genome and environment wide associations in type 2 diabetes mellitus
Human Genetics, 2013Co-Authors: Chirag J Patel, Rong Chen, Keiichi Kodama, John P A Ioannidis, Atul J ButteAbstract:Diseases such as type 2 diabetes (T2D) result from environmental and genetic factors, and risk varies considerably in the population. T2D-related genetic loci discovered to date explain only a small portion of the T2D heritability. Some heritability may be due to gene–environment interactions. However, documenting these interactions has been difficult due to low availability of concurrent genetic and environmental measures, selection bias, and challenges in controlling for multiple hypothesis testing. Through genome-wide association studies (GWAS), investigators have identified over 90 single nucleotide polymorphisms (SNPs) associated to T2D. Using a method analogous to GWAS [environment-wide association study (EWAS)], we found five environmental factors associated with the disease. By focusing on risk factors that emerge from GWAS and EWAS, it is possible to overcome difficulties in uncovering gene–environment interactions. Using data from the National Health and Nutrition Examination Survey (NHANES), we screened 18 SNPs and 5 serum-based environmental factors for interaction in association to T2D. We controlled for multiple hypotheses using false discovery rate (FDR) and Bonferroni Correction and found four interactions with FDR <20 %. The interaction between rs13266634 (SLC30A8) and trans-β-carotene withstood Bonferroni Correction (corrected p = 0.006, FDR <1.5 %). The per-risk-allele effect sizes in subjects with low levels of trans-β-carotene were 40 % greater than the marginal effect size [odds ratio (OR) 1.8, 95 % CI 1.3–2.6]. We hypothesize that impaired function driven by rs13266634 increases T2D risk when combined with serum levels of nutrients. Unbiased consideration of environmental and genetic factors may help identify larger and more relevant effect sizes for disease associations.
Kimmo Kontula - One of the best experts on this subject based on the ideXlab platform.
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human essential hypertension no significant association of polygenic risk scores with antihypertensive drug responses
Scientific Reports, 2020Co-Authors: Heini Sanez Tahtisalo, Sanni Ruotsalainen, Nina Mars, Kimmo Porthan, Lasse Oikarinen, Juha Virolainen, Frej Fyhrquist, Samuli Ripatti, Kimmo KontulaAbstract:Polygenic risk scores (PRSs) for essential hypertension, calculated from > 900 genomic loci, were recently found to explain a significant fraction of hypertension heritability and complications. To investigate whether variation of hypertension PRS also captures variation of antihypertensive drug responsiveness, we calculated two different PRSs for both systolic and diastolic blood pressure: one based on the top 793 independent hypertension-associated single nucleotide polymorphisms and another based on over 1 million genome-wide variants. Using our pharmacogenomic GENRES study comprising four different antihypertensive monotherapies (n ~ 200 for all drugs), we identified a weak, but (after Bonferroni Correction) statistically nonsignificant association of higher genome-wide PRSs with weaker response to a diuretic. In addition, we noticed a correlation between high genome-wide PRS and electrocardiographic left ventricular hypertrophy. Finally, using data of the Finnish arm of the LIFE study (n = 346), we found that PRSs for systolic blood pressure were slightly higher in patients with drug-resistant hypertension than in those with drug-controlled hypertension (p = 0.03, not significant after Bonferroni Correction). In conclusion, our results indicate that patients with elevated hypertension PRSs may be predisposed to difficult-to-control hypertension and complications thereof. No general association between a high PRS and less efficient drug responsiveness was noticed.
Kimmo Porthan - One of the best experts on this subject based on the ideXlab platform.
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human essential hypertension no significant association of polygenic risk scores with antihypertensive drug responses
Scientific Reports, 2020Co-Authors: Heini Sanez Tahtisalo, Sanni Ruotsalainen, Nina Mars, Kimmo Porthan, Lasse Oikarinen, Juha Virolainen, Frej Fyhrquist, Samuli Ripatti, Kimmo KontulaAbstract:Polygenic risk scores (PRSs) for essential hypertension, calculated from > 900 genomic loci, were recently found to explain a significant fraction of hypertension heritability and complications. To investigate whether variation of hypertension PRS also captures variation of antihypertensive drug responsiveness, we calculated two different PRSs for both systolic and diastolic blood pressure: one based on the top 793 independent hypertension-associated single nucleotide polymorphisms and another based on over 1 million genome-wide variants. Using our pharmacogenomic GENRES study comprising four different antihypertensive monotherapies (n ~ 200 for all drugs), we identified a weak, but (after Bonferroni Correction) statistically nonsignificant association of higher genome-wide PRSs with weaker response to a diuretic. In addition, we noticed a correlation between high genome-wide PRS and electrocardiographic left ventricular hypertrophy. Finally, using data of the Finnish arm of the LIFE study (n = 346), we found that PRSs for systolic blood pressure were slightly higher in patients with drug-resistant hypertension than in those with drug-controlled hypertension (p = 0.03, not significant after Bonferroni Correction). In conclusion, our results indicate that patients with elevated hypertension PRSs may be predisposed to difficult-to-control hypertension and complications thereof. No general association between a high PRS and less efficient drug responsiveness was noticed.