SwePub
Sök i SwePub databas

  Utökad sökning

Träfflista för sökning "WFRF:(Yaghootkar Hanieh) "

Sökning: WFRF:(Yaghootkar Hanieh)

  • Resultat 1-10 av 40
  • [1]234Nästa
Sortera/gruppera träfflistan
   
NumreringReferensOmslagsbildHitta
1.
  • Kanoni, Stavroula, et al. (författare)
  • Analysis with the exome array identifies multiple new independent variants in lipid loci
  • 2016
  • Ingår i: Human Molecular Genetics. - Oxford University Press. - 0964-6906. ; 25:18, s. 4094-4106
  • Tidskriftsartikel (refereegranskat)abstract
    • It has been hypothesized that low frequency (1-5% minor allele frequency (MAF)) and rare (<1% MAF) variants with large effect sizes may contribute to the missing heritability in complex traits. Here, we report an association analysis of lipid traits (total cholesterol, LDL-cholesterol, HDL-cholesterol triglycerides) in up to 27 312 individuals with a comprehensive set of low frequency coding variants (ExomeChip), combined with conditional analysis in the known lipid loci. No new locus reached genome-wide significance. However, we found a new lead variant in 26 known lipid association regions of which 16 were > 1000-fold more significant than the previous sentinel variant and not in close LD (six had MAF < 5%). Furthermore, conditional analysis revealed multiple independent signals (ranging from 1 to 5) in a third of the 98 lipid loci tested, including rare variants. Addition of our novel associations resulted in between 1.5- and 2.5-fold increase in the proportion of heritability explained for the different lipid traits. Our findings suggest that rare coding variants contribute to the genetic architecture of lipid traits.
  •  
2.
  • Wessel, Jennifer, et al. (författare)
  • Low-frequency and rare exome chip variants associate with fasting glucose and type 2 diabetes susceptibility
  • 2015
  • Ingår i: Nature communications. - 2041-1723. ; 6, s. 5897
  • Tidskriftsartikel (refereegranskat)abstract
    • Fasting glucose and insulin are intermediate traits for type 2 diabetes. Here we explore the role of coding variation on these traits by analysis of variants on the HumanExome BeadChip in 60,564 non-diabetic individuals and in 16,491 T2D cases and 81,877 controls. We identify a novel association of a low-frequency nonsynonymous SNV in GLP1R (A316T; rs10305492; MAF=1.4%) with lower FG (β=-0.09±0.01 mmol l(-1), P=3.4 × 10(-12)), T2D risk (OR[95%CI]=0.86[0.76-0.96], P=0.010), early insulin secretion (β=-0.07±0.035 pmolinsulin mmolglucose(-1), P=0.048), but higher 2-h glucose (β=0.16±0.05 mmol l(-1), P=4.3 × 10(-4)). We identify a gene-based association with FG at G6PC2 (pSKAT=6.8 × 10(-6)) driven by four rare protein-coding SNVs (H177Y, Y207S, R283X and S324P). We identify rs651007 (MAF=20%) in the first intron of ABO at the putative promoter of an antisense lncRNA, associating with higher FG (β=0.02±0.004 mmol l(-1), P=1.3 × 10(-8)). Our approach identifies novel coding variant associations and extends the allelic spectrum of variation underlying diabetes-related quantitative traits and T2D susceptibility.
3.
  • Beaumont, Robin N, et al. (författare)
  • Genome-wide association study of offspring birth weight in 86,577 women identifies five novel loci and highlights maternal genetic effects that are independent of fetal genetics.
  • 2018
  • Ingår i: Human molecular genetics. - 1460-2083 .- 1460-2083. ; 27:4, s. 742-756
  • Tidskriftsartikel (refereegranskat)abstract
    • Genome-wide association studies (GWAS) of birth weight have focused on fetal genetics, while relatively little is known about the role of maternal genetic variation. We aimed to identify maternal genetic variants associated with birth weight that could highlight potentially relevant maternal determinants of fetal growth. We meta-analysed data on up to 8.7 million SNPs in up to 86,577 women of European descent from the Early Growth Genetics (EGG) Consortium and the UK Biobank. We used structural equation modelling (SEM) and analyses of mother-child pairs to quantify the separate maternal and fetal genetic effects. Maternal SNPs at 10 loci (MTNR1B, HMGA2, SH2B3, KCNAB1, L3MBTL3, GCK, EBF1, TCF7L2, ACTL9, CYP3A7) were associated with offspring birth weight at P<5x10-8. In SEM analyses, at least 7 of the 10 associations were consistent with effects of the maternal genotype acting via the intrauterine environment, rather than via effects of shared alleles with the fetus. Variants, or correlated proxies, at many of the loci had been previously associated with adult traits, including fasting glucose (MTNR1B, GCK and TCF7L2) and sex hormone levels (CYP3A7), and one (EBF1) with gestational duration. The identified associations indicate genetic effects on maternal glucose, cytochrome P450 activity and gestational duration, and potentially on maternal blood pressure and immune function, are relevant for fetal growth. Further characterization of these associations in mechanistic and causal analyses will enhance understanding of the potentially modifiable maternal determinants of fetal growth, with the goal of reducing the morbidity and mortality associated with low and high birth weights.
  •  
4.
  • Erzurumluoglu, A Mesut, et al. (författare)
  • Meta-analysis of up to 622,409 individuals identifies 40 novel smoking behaviour associated genetic loci
  • 2019
  • Ingår i: Molecular Psychiatry. - Nature Publishing Group. - 1359-4184 .- 1476-5578.
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Smoking is a major heritable and modifiable risk factor for many diseases, including cancer, common respiratory disorders and cardiovascular diseases. Fourteen genetic loci have previously been associated with smoking behaviour-related traits. We tested up to 235,116 single nucleotide variants (SNVs) on the exome-array for association with smoking initiation, cigarettes per day, pack-years, and smoking cessation in a fixed effects meta-analysis of up to 61 studies (up to 346,813 participants). In a subset of 112,811 participants, a further one million SNVs were also genotyped and tested for association with the four smoking behaviour traits. SNV-trait associations with P &lt; 5 × 10<sup>-8</sup> in either analysis were taken forward for replication in up to 275,596 independent participants from UK Biobank. Lastly, a meta-analysis of the discovery and replication studies was performed. Sixteen SNVs were associated with at least one of the smoking behaviour traits (P &lt; 5 × 10<sup>-8</sup>) in the discovery samples. Ten novel SNVs, including rs12616219 near TMEM182, were followed-up and five of them (rs462779 in REV3L, rs12780116 in CNNM2, rs1190736 in GPR101, rs11539157 in PJA1, and rs12616219 near TMEM182) replicated at a Bonferroni significance threshold (P &lt; 4.5 × 10<sup>-3</sup>) with consistent direction of effect. A further 35 SNVs were associated with smoking behaviour traits in the discovery plus replication meta-analysis (up to 622,409 participants) including a rare SNV, rs150493199, in CCDC141 and two low-frequency SNVs in CEP350 and HDGFRP2. Functional follow-up implied that decreased expression of REV3L may lower the probability of smoking initiation. The novel loci will facilitate understanding the genetic aetiology of smoking behaviour and may lead to the identification of potential drug targets for smoking prevention and/or cessation.</p>
  •  
5.
  • Fall, Tove, et al. (författare)
  • Using genetic variants to assess the relationship between circulating lipids and type 2 diabetes.
  • 2015
  • Ingår i: Diabetes. - American Diabetes Association Inc.. - 1939-327X. ; 64:7, s. 2676-2684
  • Tidskriftsartikel (refereegranskat)abstract
    • The effects of dyslipidemia on the risk of type 2 diabetes (T2D) and related traits are not clear. We used regression models and 140 lipid-associated genetic variants to estimate associations between circulating HDL-cholesterol, LDL-cholesterol and triglycerides, and T2D and related traits. Each genetic test was corrected for effects of variants on the other two lipid types and surrogates of adiposity. We used the largest datasets available - 34,840 T2D cases and 114,981 controls from the DIAGRAM consortium and up to 133,010 non-diabetic individuals for insulin secretion and sensitivity, from the MAGIC and GENESIS studies.Eight out of 21 associations between groups of variants and diabetes traits were significant at the nominal level, including those between genetically determined lower HDL-C (β=-0.12, P=0.03) and T2D, and genetically determined lower LDL-C (β =-0.21, P=5x10(-6)) and T2D. While some of these may represent causal associations, we discuss why caution must be used when using Mendelian randomization in the context of circulating lipid levels and diabetes traits. In conclusion, we found evidence of links between genetic variants associated with lipids and T2D, but deepened knowledge of the underlying genetic mechanisms of specific lipid variants is needed before drawing definite conclusions about causality using Mendelian randomization methodology.
  •  
6.
  • Horikoshi, Momoko, et al. (författare)
  • New loci associated with birth weight identify genetic links between intrauterine growth and adult height and metabolism.
  • 2013
  • Ingår i: Nature Genetics. - 1061-4036 .- 1546-1718. ; 45:1
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Birth weight within the normal range is associated with a variety of adult-onset diseases, but the mechanisms behind these associations are poorly understood. Previous genome-wide association studies of birth weight identified a variant in the ADCY5 gene associated both with birth weight and type 2 diabetes and a second variant, near CCNL1, with no obvious link to adult traits. In an expanded genome-wide association meta-analysis and follow-up study of birth weight (of up to 69,308 individuals of European descent from 43 studies), we have now extended the number of loci associated at genome-wide significance to 7, accounting for a similar proportion of variance as maternal smoking. Five of the loci are known to be associated with other phenotypes: ADCY5 and CDKAL1 with type 2 diabetes, ADRB1 with adult blood pressure and HMGA2 and LCORL with adult height. Our findings highlight genetic links between fetal growth and postnatal growth and metabolism.</p>
  •  
7.
  • Ji, Yingjie, et al. (författare)
  • Genome-wide and abdominal MRI data provide evidence that a genetically determined favorable adiposity phenotype is characterized by lower ectopic liver fat and lower risk of type 2 diabetes, heart disease, and hypertension
  • 2019
  • Ingår i: Diabetes. - American Diabetes Association Inc.. - 0012-1797. ; 68:1, s. 207-219
  • Tidskriftsartikel (refereegranskat)abstract
    • Recent genetic studies have identified alleles associated with opposite effects on adiposity and risk of type 2 diabetes. We aimed to identify more of these variants and test the hypothesis that such favorable adiposity alleles are associated with higher subcutaneous fat and lower ectopic fat. We combined MRI data with genome-wide association studies of body fat percentage (%) and metabolic traits. We report 14 alleles, including 7 newly characterized alleles, associated with higher adiposity but a favorable metabolic profile. Consistent with previous studies, individuals carrying more favorable adiposity alleles had higher body fat % and higher BMI but lower risk of type 2 diabetes, heart disease, and hypertension. These individuals also had higher subcutaneous fat but lower liver fat and a lower visceral-to-subcutaneous adipose tissue ratio. Individual alleles associated with higher body fat % but lower liver fat and lower risk of type 2 diabetes included those in PPARG, GRB14, and IRS1, whereas the allele in ANKRD55 was paradoxically associated with higher visceral fat but lower risk of type 2 diabetes. Most identified favorable adiposity alleles are associated with higher subcutaneous and lower liver fat, a mechanism consistent with the beneficial effects of storing excess triglycerides in metabolically low-risk depots.
  •  
8.
  • Ji, Yingjie, et al. (författare)
  • Genome-Wide and Abdominal MRI Data Provide Evidence That a Genetically Determined Favorable Adiposity Phenotype Is Characterized by Lower Ectopic Liver Fat and Lower Risk of Type 2 Diabetes, Heart Disease, and Hypertension
  • 2019
  • Ingår i: Diabetes. - The American Diabetes Association. - 0012-1797 .- 1939-327X. ; 68:1, s. 207-219
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Recent genetic studies have identified alleles associated with opposite effects on adiposity and risk of type 2 diabetes. We aimed to identify more of these variants and test the hypothesis that such favorable adiposity alleles are associated with higher subcutaneous fat and lower ectopic fat. We combined MRI data with genome-wide association studies of body fat percentage (%) and metabolic traits. We report 14 alleles, including 7 newly characterized alleles, associated with higher adiposity but a favorable metabolic profile. Consistent with previous studies, individuals carrying more favorable adiposity alleles had higher body fat % and higher BMI but lower risk of type 2 diabetes, heart disease, and hypertension. These individuals also had higher subcutaneous fat but lower liver fat and a lower visceral-to-subcutaneous adipose tissue ratio. Individual alleles associated with higher body fat % but lower liver fat and lower risk of type 2 diabetes included those in <em>PPARG</em>, <em>GRB14</em>, and <em>IRS1</em>, whereas the allele in <em>ANKRD55</em> was paradoxically associated with higher visceral fat but lower risk of type 2 diabetes. Most identified favorable adiposity alleles are associated with higher subcutaneous and lower liver fat, a mechanism consistent with the beneficial effects of storing excess triglycerides in metabolically low-risk depots.</p>
  •  
9.
  • Justice, Anne E., et al. (författare)
  • Protein-coding variants implicate novel genes related to lipid homeostasis contributing to body-fat distribution
  • 2019
  • Ingår i: Nature Genetics. - Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:3, s. 452-469
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Body-fat distribution is a risk factor for adverse cardiovascular health consequences. We analyzed the association of body-fat distribution, assessed by waist-to-hip ratio adjusted for body mass index, with 228,985 predicted coding and splice site variants available on exome arrays in up to 344,369 individuals from five major ancestries (discovery) and 132,177 European-ancestry individuals (validation). We identified 15 common (minor allele frequency, MAF &gt;= 5%) and nine low-frequency or rare (MAF &lt; 5%) coding novel variants. Pathway/gene set enrichment analyses identified lipid particle, adiponectin, abnormal white adipose tissue physiology and bone development and morphology as important contributors to fat distribution, while cross-trait associations highlight cardiometabolic traits. In functional follow-up analyses, specifically in Drosophila RNAi-knockdowns, we observed a significant increase in the total body triglyceride levels for two genes (DNAH10 and PLXND1). We implicate novel genes in fat distribution, stressing the importance of interrogating low-frequency and protein-coding variants.</p>
  •  
10.
  • Kanoni, Stavroula, et al. (författare)
  • Analysis with the exome array identifies multiple new independent variants in lipid loci
  • 2016
  • Ingår i: Human Molecular Genetics. - 0964-6906 .- 1460-2083. ; 25:18, s. 4094-4106
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>It has been hypothesized that low frequency (1-5% minor allele frequency (MAF)) and rare (&lt;1% MAF) variants with large effect sizes may contribute to the missing heritability in complex traits. Here, we report an association analysis of lipid traits (total cholesterol, LDL-cholesterol, HDL-cholesterol triglycerides) in up to 27 312 individuals with a comprehensive set of low frequency coding variants (ExomeChip), combined with conditional analysis in the known lipid loci. No new locus reached genome-wide significance. However, we found a new lead variant in 26 known lipid association regions of which 16 were &gt;1000-fold more significant than the previous sentinel variant and not in close LD (six had MAF &lt;5%). Furthermore, conditional analysis revealed multiple independent signals (ranging from 1 to 5) in a third of the 98 lipid loci tested, including rare variants. Addition of our novel associations resulted in between 1.5- and 2.5-fold increase in the proportion of heritability explained for the different lipid traits. Our findings suggest that rare coding variants contribute to the genetic architecture of lipid traits.</p>
  •  
Skapa referenser, mejla, bekava och länka
  • Resultat 1-10 av 40
  • [1]234Nästa
Åtkomst
fritt online (5)
Typ av publikation
tidskriftsartikel (39)
forskningsöversikt (1)
Typ av innehåll
refereegranskat (40)
övrigt vetenskapligt (1)
Författare/redaktör
Yaghootkar, Hanieh (40)
McCarthy, Mark I (29)
Scott, Robert A (29)
Langenberg, Claudia (26)
Frayling, Timothy M. (26)
Mohlke, Karen L (24)
visa fler...
Franks, Paul W, (22)
Laakso, Markku, (22)
Deloukas, Panos (21)
Wareham, Nicholas J (21)
Kuusisto, Johanna, (21)
Pedersen, Oluf, (21)
Hansen, Torben, (21)
Willems, Sara M. (21)
Rolandsson, Olov, (20)
Boehnke, Michael (20)
Ingelsson, Erik (19)
Hayward, Caroline (19)
Zeggini, Eleftheria (19)
Linneberg, Allan, (18)
Grarup, Niels, (18)
Hattersley, Andrew T (18)
Stancáková, Alena, (17)
Varga, Tibor V (17)
Luan, Jian'an (17)
Uitterlinden, Andre ... (16)
Bork-Jensen, Jette, (16)
Salomaa, Veikko (16)
Perola, Markus (16)
Boerwinkle, Eric (16)
Boeing, Heiner (15)
Meigs, James B. (15)
Balkau, Beverley (15)
Sattar, Naveed (15)
Hivert, Marie-France (15)
Forouhi, Nita G. (15)
Walker, Mark (15)
Amouyel, Philippe (14)
Rotter, Jerome I. (14)
Van Duijn, Cornelia ... (14)
Barroso, Inês (14)
Polasek, Ozren (14)
Morris, Andrew P. (14)
Tuomilehto, Jaakko (14)
Munroe, Patricia B. (14)
Rudan, Igor (14)
Loos, Ruth J. F. (14)
Dupuis, Josée (14)
Pankow, James S. (14)
Mahajan, Anubha (14)
visa färre...
Lärosäte
Umeå universitet (13)
Lunds universitet (10)
Uppsala universitet (8)
Göteborgs universitet (4)
Karolinska Institutet (3)
Luleå tekniska universitet (2)
visa fler...
Mittuniversitetet (2)
Stockholms universitet (1)
visa färre...
Språk
Engelska (40)
Forskningsämne (UKÄ/SCB)
Medicin och hälsovetenskap (37)
Naturvetenskap (2)

År

 
pil uppåt Stäng

Kopiera och spara länken för att återkomma till aktuell vy