SwePub
Sök i SwePub databas

  form:Ext_t

Träfflista för sökning "WFRF:(Wareham Nicholas J.) "

form:Search_simp_t: WFRF:(Wareham Nicholas J.)

  • navigation:Result_t 1-10 navigation:of_t 293
hitlist:Modify_result_t
   
hitlist:Enumeration_thitlist:Reference_thitlist:Reference_picture_thitlist:Find_Mark_t
1.
  • Kanoni, Stavroula, et al. (creator_code:aut_t)
  • Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.
  • 2022
  • record:In_t: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 23:1
  • swepub:Mat_article_t (swepub:level_refereed_t)abstract
    • Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism.Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.
  •  
2.
  • Joshi, Peter K, et al. (creator_code:aut_t)
  • Directional dominance on stature and cognition in diverse human populations
  • 2015
  • record:In_t: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 523:7561, s. 459-462
  • swepub:Mat_article_t (swepub:level_refereed_t)abstract
    • Homozygosity has long been associated with rare, often devastating, Mendelian disorders, and Darwin was one of the first to recognize that inbreeding reduces evolutionary fitness. However, the effect of the more distant parental relatedness that is common in modern human populations is less well understood. Genomic data now allow us to investigate the effects of homozygosity on traits of public health importance by observing contiguous homozygous segments (runs of homozygosity), which are inferred to be homozygous along their complete length. Given the low levels of genome-wide homozygosity prevalent in most human populations, information is required on very large numbers of people to provide sufficient power. Here we use runs of homozygosity to study 16 health-related quantitative traits in 354,224 individuals from 102 cohorts, and find statistically significant associations between summed runs of homozygosity and four complex traits: height, forced expiratory lung volume in one second, general cognitive ability and educational attainment (P < 1 × 10(-300), 2.1 × 10(-6), 2.5 × 10(-10) and 1.8 × 10(-10), respectively). In each case, increased homozygosity was associated with decreased trait value, equivalent to the offspring of first cousins being 1.2 cm shorter and having 10 months' less education. Similar effect sizes were found across four continental groups and populations with different degrees of genome-wide homozygosity, providing evidence that homozygosity, rather than confounding, directly contributes to phenotypic variance. Contrary to earlier reports in substantially smaller samples, no evidence was seen of an influence of genome-wide homozygosity on blood pressure and low density lipoprotein cholesterol, or ten other cardio-metabolic traits. Since directional dominance is predicted for traits under directional evolutionary selection, this study provides evidence that increased stature and cognitive function have been positively selected in human evolution, whereas many important risk factors for late-onset complex diseases may not have been.
  •  
3.
  • Palmer, Nicholette D, et al. (creator_code:aut_t)
  • A genome-wide association search for type 2 diabetes genes in African Americans.
  • 2012
  • record:In_t: PloS one. - San Francisco : Public Library of Science (PLoS). - 1932-6203. ; 7:1, s. e29202-
  • swepub:Mat_article_t (swepub:level_refereed_t)abstract
    • African Americans are disproportionately affected by type 2 diabetes (T2DM) yet few studies have examined T2DM using genome-wide association approaches in this ethnicity. The aim of this study was to identify genes associated with T2DM in the African American population. We performed a Genome Wide Association Study (GWAS) using the Affymetrix 6.0 array in 965 African-American cases with T2DM and end-stage renal disease (T2DM-ESRD) and 1029 population-based controls. The most significant SNPs (n = 550 independent loci) were genotyped in a replication cohort and 122 SNPs (n = 98 independent loci) were further tested through genotyping three additional validation cohorts followed by meta-analysis in all five cohorts totaling 3,132 cases and 3,317 controls. Twelve SNPs had evidence of association in the GWAS (P<0.0071), were directionally consistent in the Replication cohort and were associated with T2DM in subjects without nephropathy (P<0.05). Meta-analysis in all cases and controls revealed a single SNP reaching genome-wide significance (P<2.5×10(-8)). SNP rs7560163 (P = 7.0×10(-9), OR (95% CI) = 0.75 (0.67-0.84)) is located intergenically between RND3 and RBM43. Four additional loci (rs7542900, rs4659485, rs2722769 and rs7107217) were associated with T2DM (P<0.05) and reached more nominal levels of significance (P<2.5×10(-5)) in the overall analysis and may represent novel loci that contribute to T2DM. We have identified novel T2DM-susceptibility variants in the African-American population. Notably, T2DM risk was associated with the major allele and implies an interesting genetic architecture in this population. These results suggest that multiple loci underlie T2DM susceptibility in the African-American population and that these loci are distinct from those identified in other ethnic populations.
  •  
4.
  • Speliotes, Elizabeth K., et al. (creator_code:aut_t)
  • Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index
  • 2010
  • record:In_t: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:11, s. 937-948
  • swepub:Mat_article_t (swepub:level_refereed_t)abstract
    • Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and ~2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SNPs in up to 125,931 additional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci associated with body mass index (P < 5 × 10−8), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly associated loci may provide new insights into human body weight regulation.
  •  
5.
  • van de Vegte, Yordi, et al. (creator_code:aut_t)
  • Genetic insights into resting heart rate and its role in cardiovascular disease
  • 2023
  • record:In_t: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1
  • swepub:Mat_article_t (swepub:level_refereed_t)abstract
    • The genetics and clinical consequences of resting heart rate (RHR) remain incompletely understood. Here, the authors discover new genetic variants associated with RHR and find that higher genetically predicted RHR decreases risk of atrial fibrillation and ischemic stroke. Resting heart rate is associated with cardiovascular diseases and mortality in observational and Mendelian randomization studies. The aims of this study are to extend the number of resting heart rate associated genetic variants and to obtain further insights in resting heart rate biology and its clinical consequences. A genome-wide meta-analysis of 100 studies in up to 835,465 individuals reveals 493 independent genetic variants in 352 loci, including 68 genetic variants outside previously identified resting heart rate associated loci. We prioritize 670 genes and in silico annotations point to their enrichment in cardiomyocytes and provide insights in their ECG signature. Two-sample Mendelian randomization analyses indicate that higher genetically predicted resting heart rate increases risk of dilated cardiomyopathy, but decreases risk of developing atrial fibrillation, ischemic stroke, and cardio-embolic stroke. We do not find evidence for a linear or non-linear genetic association between resting heart rate and all-cause mortality in contrast to our previous Mendelian randomization study. Systematic alteration of key differences between the current and previous Mendelian randomization study indicates that the most likely cause of the discrepancy between these studies arises from false positive findings in previous one-sample MR analyses caused by weak-instrument bias at lower P-value thresholds. The results extend our understanding of resting heart rate biology and give additional insights in its role in cardiovascular disease development.
  •  
6.
  • Surendran, Praveen, et al. (creator_code:aut_t)
  • Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals
  • 2020
  • record:In_t: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 52:12, s. 1314-1332
  • swepub:Mat_article_t (swepub:level_refereed_t)abstract
    • Genetic studies of blood pressure (BP) to date have mainly analyzed common variants (minor allele frequency > 0.05). In a meta-analysis of up to similar to 1.3 million participants, we discovered 106 new BP-associated genomic regions and 87 rare (minor allele frequency <= 0.01) variant BP associations (P < 5 x 10(-8)), of which 32 were in new BP-associated loci and 55 were independent BP-associated single-nucleotide variants within known BP-associated regions. Average effects of rare variants (44% coding) were similar to 8 times larger than common variant effects and indicate potential candidate causal genes at new and known loci (for example, GATA5 and PLCB3). BP-associated variants (including rare and common) were enriched in regions of active chromatin in fetal tissues, potentially linking fetal development with BP regulation in later life. Multivariable Mendelian randomization suggested possible inverse effects of elevated systolic and diastolic BP on large artery stroke. Our study demonstrates the utility of rare-variant analyses for identifying candidate genes and the results highlight potential therapeutic targets.
  •  
7.
  • Evangelou, Evangelos, et al. (creator_code:aut_t)
  • Genetic analysis of over 1 million people identifies 535 new loci associated with blood pressure traits.
  • 2018
  • record:In_t: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 50:10, s. 1412-1425
  • swepub:Mat_article_t (swepub:level_refereed_t)abstract
    • High blood pressure is a highly heritable and modifiable risk factor for cardiovascular disease. We report the largest genetic association study of blood pressure traits (systolic, diastolic and pulse pressure) to date in over 1 million people of European ancestry. We identify 535 novel blood pressure loci that not only offer new biological insights into blood pressure regulation but also highlight shared genetic architecture between blood pressure and lifestyle exposures. Our findings identify new biological pathways for blood pressure regulation with potential for improved cardiovascular disease prevention in the future.
  •  
8.
  • Heid, Iris M, et al. (creator_code:aut_t)
  • Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution
  • 2010
  • record:In_t: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:11, s. 949-960
  • swepub:Mat_article_t (swepub:level_refereed_t)abstract
    • Waist-hip ratio (WHR) is a measure of body fat distribution and a predictor of metabolic consequences independent of overall adiposity. WHR is heritable, but few genetic variants influencing this trait have been identified. We conducted a meta-analysis of 32 genome-wide association studies for WHR adjusted for body mass index (comprising up to 77,167 participants), following up 16 loci in an additional 29 studies (comprising up to 113,636 subjects). We identified 13 new loci in or near RSPO3, VEGFA, TBX15-WARS2, NFE2L3, GRB14, DNM3-PIGC, ITPR2-SSPN, LY86, HOXC13, ADAMTS9, ZNRF3-KREMEN1, NISCH-STAB1 and CPEB4 (P = 1.9 × 10⁻⁹ to P = 1.8 × 10⁻⁴⁰) and the known signal at LYPLAL1. Seven of these loci exhibited marked sexual dimorphism, all with a stronger effect on WHR in women than men (P for sex difference = 1.9 × 10⁻³ to P = 1.2 × 10⁻¹³). These findings provide evidence for multiple loci that modulate body fat distribution independent of overall adiposity and reveal strong gene-by-sex interactions.
  •  
9.
  • Locke, Adam E, et al. (creator_code:aut_t)
  • Genetic studies of body mass index yield new insights for obesity biology.
  • 2015
  • record:In_t: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 197-401
  • swepub:Mat_article_t (swepub:level_refereed_t)abstract
    • Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.
  •  
10.
  • Turcot, Valerie, et al. (creator_code:aut_t)
  • Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity
  • 2018
  • record:In_t: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 50:1, s. 26-41
  • swepub:Mat_article_t (swepub:level_refereed_t)abstract
    • Genome-wide association studies (GWAS) have identified >250 loci for body mass index (BMI), implicating pathways related to neuronal biology. Most GWAS loci represent clusters of common, noncoding variants from which pinpointing causal genes remains challenging. Here we combined data from 718,734 individuals to discover rare and low-frequency (minor allele frequency (MAF) < 5%) coding variants associated with BMI. We identified 14 coding variants in 13 genes, of which 8 variants were in genes (ZBTB7B, ACHE, RAPGEF3, RAB21, ZFHX3, ENTPD6, ZFR2 and ZNF169) newly implicated in human obesity, 2 variants were in genes (MC4R and KSR2) previously observed to be mutated in extreme obesity and 2 variants were in GIPR. The effect sizes of rare variants are similar to 10 times larger than those of common variants, with the largest effect observed in carriers of an MC4R mutation introducing a stop codon (p.Tyr35Ter, MAF = 0.01%), who weighed similar to 7 kg more than non-carriers. Pathway analyses based on the variants associated with BMI confirm enrichment of neuronal genes and provide new evidence for adipocyte and energy expenditure biology, widening the potential of genetically supported therapeutic targets in obesity.
  •  
Skapa referenser, mejla, bekava och länka
  • navigation:Result_t 1-10 navigation:of_t 293
swepub:Mat_t
swepub:mat_article_t (288)
swepub:mat_publicationother_t (2)
swepub:mat_researchreview_t (2)
swepub:mat_conferencepaper_t (1)
swepub:Level_t
swepub:level_refereed_t (290)
swepub:level_scientificother_t (3)
swepub:Hitlist_author_t
Wareham, Nicholas J. (252)
Boeing, Heiner (137)
Riboli, Elio (129)
Tumino, Rosario (128)
Overvad, Kim (124)
Khaw, Kay-Tee (122)
deldatabas:search_more_t
Langenberg, Claudia (121)
Trichopoulou, Antoni ... (93)
Palli, Domenico (93)
Kaaks, Rudolf (91)
Tjonneland, Anne (91)
Panico, Salvatore (88)
Loos, Ruth J F (82)
Forouhi, Nita G. (76)
Luan, Jian'an (72)
Sacerdote, Carlotta (68)
Boutron-Ruault, Mari ... (65)
Sánchez, Maria-José (64)
McCarthy, Mark I (64)
Barricarte, Aurelio (63)
Weiderpass, Elisabet ... (63)
Boehnke, Michael (63)
Laakso, Markku (60)
Scott, Robert A (60)
Barroso, Ines (60)
Franks, Paul W. (58)
Mohlke, Karen L (56)
Key, Timothy J (55)
Rolandsson, Olov (55)
Sharp, Stephen J. (55)
Fagherazzi, Guy (54)
Zhao, Jing Hua (54)
Deloukas, Panos (53)
van der Schouw, Yvon ... (52)
Salomaa, Veikko (51)
Tuomilehto, Jaakko (51)
Slimani, Nadia (51)
Hofman, Albert (51)
Lind, Lars (50)
Uitterlinden, André ... (50)
Clavel-Chapelon, Fra ... (49)
Kuusisto, Johanna (49)
Hayward, Caroline (49)
Morris, Andrew P. (49)
Ardanaz, Eva (48)
Gieger, Christian (48)
Bueno-de-Mesquita, H ... (47)
Schulze, Matthias B. (46)
Gudnason, Vilmundur (46)
Jackson, Anne U. (46)
deldatabas:search_less_t
swepub:Hitlist_uni_t
swepub_uni:umu_t (174)
swepub_uni:lu_t (161)
swepub_uni:uu_t (79)
swepub_uni:ki_t (48)
swepub_uni:gu_t (26)
swepub_uni:oru_t (7)
deldatabas:search_more_t
swepub_uni:su_t (5)
swepub_uni:slu_t (4)
swepub_uni:ltu_t (3)
swepub_uni:hkr_t (1)
swepub_uni:liu_t (1)
deldatabas:search_less_t
hitlist:Language_t
language:Eng_t (293)
hitlist:HSV_t
hsv:Cat_3_t (233)
hsv:Cat_1_t (7)
hsv:Cat_5_t (2)

hitlist:Year_t

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.

 
pil uppåt tools:Close_t

tools:Permalink_label_t