SwePub
Sök i SwePub databas

  Utökad sökning

Träfflista för sökning "WFRF:(Perola Markus) "

Sökning: WFRF:(Perola Markus)

  • Resultat 61-70 av 92
Sortera/gruppera träfflistan
   
NumreringReferensOmslagsbildHitta
61.
  • Ollila, Hanna M., et al. (författare)
  • Narcolepsy risk loci outline role of T cell autoimmunity and infectious triggers in narcolepsy
  • 2023
  • Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 14
  • Tidskriftsartikel (refereegranskat)abstract
    • Narcolepsy type 1 (NT1) is caused by a loss of hypocretin/orexin transmission. Risk factors include pandemic 2009 H1N1 influenza A infection and immunization with Pandemrix (R). Here, we dissect disease mechanisms and interactions with environmental triggers in a multi-ethnic sample of 6,073 cases and 84,856 controls. We fine-mapped GWAS signals within HLA (DQ0602, DQB1*03:01 and DPB1*04:02) and discovered seven novel associations (CD207, NAB1, IKZF4-ERBB3, CTSC, DENND1B, SIRPG, PRF1). Significant signals at TRA and DQB1*06:02 loci were found in 245 vaccination-related cases, who also shared polygenic risk. T cell receptor associations in NT1 modulated TRAJ*24, TRAJ*28 and TRBV*4-2 chain-usage. Partitioned heritability and immune cell enrichment analyses found genetic signals to be driven by dendritic and helper T cells. Lastly comorbidity analysis using data from FinnGen, suggests shared effects between NT1 and other autoimmune diseases. NT1 genetic variants shape autoimmunity and response to environmental triggers, including influenza A infection and immunization with Pandemrix (R).
  •  
62.
  • Palmer, Nicholette D, et al. (författare)
  • A genome-wide association search for type 2 diabetes genes in African Americans.
  • 2012
  • Ingår i: PloS one. - San Francisco : Public Library of Science (PLoS). - 1932-6203. ; 7:1, s. e29202-
  • Tidskriftsartikel (refereegranskat)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.
  •  
63.
  • Prokic, Ivana, et al. (författare)
  • A cross-omics integrative study of metabolic signatures of chronic obstructive pulmonary disease
  • 2020
  • Ingår i: BMC Pulmonary Medicine. - : Springer Science and Business Media LLC. - 1471-2466. ; 20:1
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundChronic obstructive pulmonary disease (COPD) is a common lung disorder characterized by persistent and progressive airflow limitation as well as systemic changes. Metabolic changes in blood may help detect COPD in an earlier stage and predict prognosis.MethodsWe conducted a comprehensive study of circulating metabolites, measured by proton Nuclear Magnetic Resonance Spectroscopy, in relation with COPD and lung function. The discovery sample consisted of 5557 individuals from two large population-based studies in the Netherlands, the Rotterdam Study and the Erasmus Rucphen Family study. Significant findings were replicated in 12,205 individuals from the Lifelines-DEEP study, FINRISK and the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) studies. For replicated metabolites further investigation of causality was performed, utilizing genetics in the Mendelian randomization approach.ResultsThere were 602 cases of COPD and 4955 controls used in the discovery meta-analysis. Our logistic regression results showed that higher levels of plasma Glycoprotein acetyls (GlycA) are significantly associated with COPD (OR = 1.16, P = 5.6 × 10− 4 in the discovery and OR = 1.30, P = 1.8 × 10− 6 in the replication sample). A bi-directional two-sample Mendelian randomization analysis suggested that circulating blood GlycA is not causally related to COPD, but that COPD causally increases GlycA levels. Using the prospective data of the same sample of Rotterdam Study in Cox-regression, we show that the circulating GlycA level is a predictive biomarker of COPD incidence (HR = 1.99, 95%CI 1.52–2.60, comparing those in the highest and lowest quartile of GlycA) but is not significantly associated with mortality in COPD patients (HR = 1.07, 95%CI 0.94–1.20).ConclusionsOur study shows that circulating blood GlycA is a biomarker of early COPD pathology.
  •  
64.
  • Qi, Qibin, et al. (författare)
  • FTO genetic variants, dietary intake and body mass index : insights from 177 330 individuals
  • 2014
  • Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 23:25, s. 6961-6972
  • Tidskriftsartikel (refereegranskat)abstract
    • FTO is the strongest known genetic susceptibility locus for obesity. Experimental studies in animals suggest the potential roles of FTO in regulating food intake. The interactive relation among FTO variants, dietary intake and body mass index (BMI) is complex and results from previous often small-scale studies in humans are highly inconsistent. We performed large-scale analyses based on data from 177 330 adults (154 439 Whites, 5776 African Americans and 17 115 Asians) from 40 studies to examine: (i) the association between the FTO-rs9939609 variant (or a proxy single-nucleotide polymorphism) and total energy and macronutrient intake and (ii) the interaction between the FTO variant and dietary intake on BMI. The minor allele (A-allele) of the FTO-rs9939609 variant was associated with higher BMI in Whites (effect per allele = 0.34 [0.31, 0.37] kg/m(2), P = 1.9 × 10(-105)), and all participants (0.30 [0.30, 0.35] kg/m(2), P = 3.6 × 10(-107)). The BMI-increasing allele of the FTO variant showed a significant association with higher dietary protein intake (effect per allele = 0.08 [0.06, 0.10] %, P = 2.4 × 10(-16)), and relative weak associations with lower total energy intake (-6.4 [-10.1, -2.6] kcal/day, P = 0.001) and lower dietary carbohydrate intake (-0.07 [-0.11, -0.02] %, P = 0.004). The associations with protein (P = 7.5 × 10(-9)) and total energy (P = 0.002) were attenuated but remained significant after adjustment for BMI. We did not find significant interactions between the FTO variant and dietary intake of total energy, protein, carbohydrate or fat on BMI. Our findings suggest a positive association between the BMI-increasing allele of FTO variant and higher dietary protein intake and offer insight into potential link between FTO, dietary protein intake and adiposity.
  •  
65.
  • Ried, Janina S., et al. (författare)
  • A principal component meta-analysis on multiple anthropometric traits identifies novel loci for body shape
  • 2016
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
  • Tidskriftsartikel (refereegranskat)abstract
    • Large consortia have revealed hundreds of genetic loci associated with anthropometric traits, one trait at a time. We examined whether genetic variants affect body shape as a composite phenotype that is represented by a combination of anthropometric traits. We developed an approach that calculates averaged PCs (AvPCs) representing body shape derived from six anthropometric traits (body mass index, height, weight, waist and hip circumference, waist-to-hip ratio). The first four AvPCs explain >99% of the variability, are heritable, and associate with cardiometabolic outcomes. We performed genome-wide association analyses for each body shape composite phenotype across 65 studies and meta-analysed summary statistics. We identify six novel loci: LEMD2 and CD47 for AvPC1, RPS6KA5/C14orf159 and GANAB for AvPC3, and ARL15 and ANP32 for AvPC4. Our findings highlight the value of using multiple traits to define complex phenotypes for discovery, which are not captured by single-trait analyses, and may shed light onto new pathways.
  •  
66.
  • Ripatti, Samuli, et al. (författare)
  • A multilocus genetic risk score for coronary heart disease: case-control and prospective cohort analyses
  • 2010
  • Ingår i: The Lancet. - 1474-547X. ; 376:9750, s. 1393-1400
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Comparison of patients with coronary heart disease and controls in genome-wide association studies has revealed several single nucleotide polymorphisms (SNPs) associated with coronary heart disease. We aimed to establish the external validity of these findings and to obtain more precise risk estimates using a prospective cohort design. Methods We tested 13 recently discovered SNPs for association with coronary heart disease in a case-control design including participants differing from those in the discovery samples (3829 participants with prevalent coronary heart disease and 48 897 controls free of the disease) and a prospective cohort design including 30 725 participants free of cardiovascular disease from Finland and Sweden. We modelled the 13 SNPs as a multilocus genetic risk score and used Cox proportional hazards models to estimate the association of genetic risk score with incident coronary heart disease. For case-control analyses we analysed associations between individual SNPs and quintiles of genetic risk score using logistic regression. Findings In prospective cohort analyses, 1264 participants had a first coronary heart disease event during a median 10.7 years' follow-up (IQR 6.7-13.6). Genetic risk score was associated with a first coronary heart disease event. When compared with the bottom quintile of genetic risk score, participants in the top quintile were at 1.66-times increased risk of coronary heart disease in a model adjusting for traditional risk factors (95% CI 1.35-2.04, p value for linear trend=7.3x10(-10)). Adjustment for family history did not change these estimates. Genetic risk score did not improve C index over traditional risk factors and family history (p=0.19), nor did it have a significant effect on net reclassification improvement (2.2%, p=0.18); however, it did have a small effect on integrated discrimination index (0.004, p=0.0006). Results of the case-control analyses were similar to those of the prospective cohort analyses. Interpretation Using a genetic risk score based on 13 SNPs associated with coronary heart disease, we can identify the 20% of individuals of European ancestry who are at roughly 70% increased risk of a first coronary heart disease event. The potential clinical use of this panel of SNPs remains to be defined.
  •  
67.
  • Saleheen, Danish, et al. (författare)
  • Loss of Cardioprotective Effects at the ADAMTS7 Locus as a Result of Gene-Smoking Interactions
  • 2017
  • Ingår i: Circulation. - 0009-7322 .- 1524-4539. ; 135:24, s. 2336-2353
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Common diseases such as coronary heart disease (CHD) are complex in etiology. The interaction of genetic susceptibility with lifestyle factors may play a prominent role. However, gene-lifestyle interactions for CHD have been difficult to identify. Here, we investigate interaction of smoking behavior, a potent lifestyle factor, with genotypes that have been shown to associate with CHD risk.METHODS: We analyzed data on 60 919 CHD cases and 80 243 controls from 29 studies for gene-smoking interactions for genetic variants at 45 loci previously reported to be associated with CHD risk. We also studied 5 loci associated with smoking behavior. Study-specific gene-smoking interaction effects were calculated and pooled using fixed-effects meta-analyses. Interaction analyses were declared to be significant at a P value of < 1.0x10-3 (Bonferroni correction for 50 tests).RESULTS: We identified novel gene-smoking interaction for a variant upstream of the ADAMTS7 gene. Every T allele of rs7178051 was associated with lower CHD risk by 12% in never-smokers (P= 1.3x10(-16)) in comparison with 5% in ever-smokers (P= 2.5x10-4), translating to a 60% loss of CHD protection conferred by this allelic variation in people who smoked tobacco (interaction P value= 8.7x10-5). The protective T allele at rs7178051 was also associated with reduced ADAMTS7 expression in human aortic endothelial cells and lymphoblastoid cell lines. Exposure of human coronary artery smooth muscle cells to cigarette smoke extract led to induction of ADAMTS7.CONCLUSIONS: Allelic variation at rs7178051 that associates with reduced ADAMTS7 expression confers stronger CHD protection in never-smokers than in ever-smokers. Increased vascular ADAMTS7 expression may contribute to the loss of CHD protection in smokers.
  •  
68.
  • Sarin, Heikki V., et al. (författare)
  • Molecular Pathways Mediating Immunosuppression in Response to Prolonged Intensive Physical Training, Low-Energy Availability, and Intensive Weight Loss
  • 2019
  • Ingår i: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 10
  • Tidskriftsartikel (refereegranskat)abstract
    • Exercise and exercise-induced weight loss have a beneficial effect on overall health, including positive effects on molecular pathways associated with immune function, especially in overweight individuals. The main aim of our study was to assess how energy deprivation (i.e., "semi-starvation") leading to substantial fat mass loss affects the immune system and immunosuppression in previously normal weight individuals. Thus, to address this hypothesis, we applied a high-throughput systems biology approach to better characterize potential key pathways associated with immune system modulation during intensive weight loss and subsequent weight regain. We examined 42 healthy female physique athletes (age 27.5 +/- 4.0 years, body mass index 23.4 +/- 1.7 kg/m(2)) volunteered into either a diet group (n = 25) or a control group (n = 17). For the diet group, the energy intake was reduced and exercise levels were increased to induce loss of fat mass that was subsequently regained during a recovery period. The control group was instructed to maintain their typical lifestyle, exercise levels, and energy intake at a constant level. For quantification of systems biology markers, fasting blood samples were drawn at three time points: baseline (PRE), at the end of the weight loss period (MID 21.1 +/- 3.1 weeks after PRE), and at the end of the weight regain period (POST 18.4 +/- 2.9 weeks after MID). In contrast to the control group, the diet group showed significant (false discovery rate <0.05) alteration of all measured immune function parameters-white blood cells (WBCs), immunoglobulin G glycome, leukocyte transcriptome, and cytokine profile. Integrative omics suggested effects on multiple levels of immune system as dysregulated hematopoiesis, suppressed immune cell proliferation, attenuated systemic inflammation, and loss of immune cell function by reduced antibody and chemokine secretion was implied after intense weight loss. During the weight regain period, the majority of the measured immune system parameters returned back to the baseline. In summary, this study elucidated a number of molecular pathways presumably explaining immunosuppression in individuals going through prolonged periods of intense training with low-energy availability. Our findings also reinforce the perception that the way in which weight loss is achieved (i.e., dietary restriction, exercise, or both) has a distinct effect on how the immune system is modulated.
  •  
69.
  • Sarin, Heikki V., et al. (författare)
  • Resistance Training Induces Antiatherogenic Effects on Metabolomic Pathways
  • 2019
  • Ingår i: Medicine & Science in Sports & Exercise. - 0195-9131 .- 1530-0315. ; 51:9, s. 1866-1875
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction Arising evidence suggests that resistance training has the potential to induce beneficial modulation of biomarker profile. To date, however, only immediate responses to resistance training have been investigated using high-throughput metabolomics whereas the effects of chronic resistance training on biomarker profile have not been studied in detail. Methods A total of 86 recreationally active healthy men without previous systematic resistance training background were allocated into (i) a resistance training (RT) group (n = 68; age, 33 ± 7 yr; body mass index, 28 ± 3 kg·m-2) and (ii) a non-RT group (n = 18; age, 31 ± 4 yr; body mass index, 27 ± 3 kg·m-2). Blood samples were collected at baseline (PRE), after 4 wk (POST-4wk), and after 16 wk of resistance training intervention (POST-16wk), as well as baseline and after the non-RT period (20-24 wk). Nuclear magnetic resonance-metabolome platform was used to determine metabolomic responses to chronic resistance training. Results Overall, the resistance training intervention resulted in favorable alterations (P < 0.05) in body composition with increased levels of lean mass (2.8%), decreased levels of android (9.6%), and total fat mass (7.5%). These changes in body composition were accompanied by antiatherogenic alterations in serum metabolome profile (false discovery rate < 0.05) as reductions in non-high-density lipoprotein cholesterol (e.g., free cholesterol, remnant cholesterol, intermediate-density lipoprotein cholesterols, low-density lipoprotein cholesterols) and related apolipoprotein B, and increments in conjugated linoleic fatty acids levels were observed. Individuals with the poorest baseline status (i.e., body composition, metabolome profile) benefitted the most from the resistance training intervention. Conclusions In conclusion, resistance training improves cardiometabolic risk factors and serum metabolome even in previously healthy young men. Thus, suggesting attenuated risk for future cardiovascular disease. 
  •  
70.
  • Scott, Robert A., et al. (författare)
  • A genomic approach to therapeutic target validation identifies a glucose-lowering GLP1R variant protective for coronary heart disease
  • 2016
  • Ingår i: Science Translational Medicine. - : American Association for the Advancement of Science (AAAS). - 1946-6234 .- 1946-6242. ; 8:341
  • Tidskriftsartikel (refereegranskat)abstract
    • Regulatory authorities have indicated that new drugs to treat type 2 diabetes (T2D) should not be associated with an unacceptable increase in cardiovascular risk. Human genetics may be able to guide development of antidiabetic therapies by predicting cardiovascular and other health endpoints. We therefore investigated the association of variants in six genes that encode drug targets for obesity or T2D with a range of metabolic traits in up to 11,806 individuals by targeted exome sequencing and follow-up in 39,979 individuals by targeted genotyping, with additional in silico follow-up in consortia. We used these data to first compare associations of variants in genes encoding drug targets with the effects of pharmacological manipulation of those targets in clinical trials. We then tested the association of those variants with disease outcomes, including coronary heart disease, to predict cardiovascular safety of these agents. A low-frequency missense variant (Ala316Thr; rs10305492) in the gene encoding glucagon-like peptide-1 receptor (GLP1R), the target of GLP1R agonists, was associated with lower fasting glucose and T2D risk, consistent with GLP1R agonist therapies. The minor allele was also associated with protection against heart disease, thus providing evidence that GLP1R agonists are not likely to be associated with an unacceptable increase in cardiovascular risk. Our results provide an encouraging signal that these agents may be associated with benefit, a question currently being addressed in randomized controlled trials. Genetic variants associated with metabolic traits and multiple disease outcomes can be used to validate therapeutic targets at an early stage in the drug development process.
  •  
Skapa referenser, mejla, bekava och länka
  • Resultat 61-70 av 92
Typ av publikation
tidskriftsartikel (90)
annan publikation (1)
doktorsavhandling (1)
Typ av innehåll
refereegranskat (89)
övrigt vetenskapligt/konstnärligt (3)
Författare/redaktör
Perola, Markus (87)
Salomaa, Veikko (59)
Metspalu, Andres (38)
Esko, Tõnu (37)
Lind, Lars (36)
McCarthy, Mark I (36)
visa fler...
van Duijn, Cornelia ... (36)
Gieger, Christian (36)
Wareham, Nicholas J. (35)
Samani, Nilesh J. (35)
Loos, Ruth J F (34)
Uitterlinden, André ... (34)
Hayward, Caroline (34)
Rudan, Igor (33)
Deloukas, Panos (33)
Ripatti, Samuli (33)
Luan, Jian'an (33)
Boehnke, Michael (32)
Hofman, Albert (31)
Kaprio, Jaakko (30)
Laakso, Markku (29)
Stefansson, Kari (29)
Mangino, Massimo (29)
Jula, Antti (28)
Langenberg, Claudia (28)
Ingelsson, Erik (28)
Thorleifsson, Gudmar (28)
Gudnason, Vilmundur (28)
Groop, Leif (27)
Campbell, Harry (27)
Mohlke, Karen L (27)
Wilson, James F. (27)
Harris, Tamara B (27)
Vollenweider, Peter (27)
Borecki, Ingrid B. (27)
Chasman, Daniel I. (26)
Tuomilehto, Jaakko (26)
Feitosa, Mary F. (26)
Lindgren, Cecilia M. (26)
Ridker, Paul M. (25)
Thorsteinsdottir, Un ... (25)
Munroe, Patricia B. (25)
Polasek, Ozren (25)
Kanoni, Stavroula (25)
Kuusisto, Johanna (24)
Willemsen, Gonneke (24)
Boomsma, Dorret I. (24)
Rivadeneira, Fernand ... (24)
Zhao, Jing Hua (24)
Boerwinkle, Eric (24)
visa färre...
Lärosäte
Uppsala universitet (46)
Lunds universitet (44)
Umeå universitet (24)
Karolinska Institutet (20)
Göteborgs universitet (9)
Stockholms universitet (2)
visa fler...
Mittuniversitetet (2)
Högskolan i Skövde (2)
Chalmers tekniska högskola (2)
Luleå tekniska universitet (1)
Linköpings universitet (1)
Handelshögskolan i Stockholm (1)
Södertörns högskola (1)
visa färre...
Språk
Engelska (91)
Odefinierat språk (1)
Forskningsämne (UKÄ/SCB)
Medicin och hälsovetenskap (75)
Naturvetenskap (11)
Samhällsvetenskap (1)

År

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 Stäng

Kopiera och spara länken för att återkomma till aktuell vy