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Sökning: onr:"swepub:oai:DiVA.org:uu-460378" > Effect of General A...

Effect of General Adiposity and Central Body Fat Distribution on the Circulating Metabolome : A Multi-Cohort Nontargeted Metabolomics Observational and Mendelian Randomization Study

Ahmad, Shafqat (författare)
Uppsala universitet,Molekylär epidemiologi,Science for Life Laboratory, SciLifeLab,Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, EpiHubben, MTC-huset, Uppsala, Sweden; Preventive Medicine Division, Harvard Medical School, Brigham and Women's Hospital, Boston, MA, United States
Hammar, Ulf (författare)
Uppsala universitet,Molekylär epidemiologi,Science for Life Laboratory, SciLifeLab,Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, EpiHubben, MTC-huset, Uppsala, Sweden
Kennedy, Beatrice, 1982- (författare)
Uppsala universitet,Molekylär epidemiologi,Science for Life Laboratory, SciLifeLab,Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, EpiHubben, MTC-huset, Uppsala, Sweden
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Salihovic, Samira, Associate Senior Lecturer, 1985- (författare)
Karolinska Institutet,Örebro universitet,Uppsala universitet,Molekylär epidemiologi,Science for Life Laboratory, SciLifeLab,School of Medical Sciences, Örebro University, Örebro, Sweden,Institutionen för medicinska vetenskaper,Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, EpiHubben, MTC-huset, Uppsala, Sweden
Ganna, Andrea (författare)
Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
Lind, Lars (författare)
Uppsala universitet,Klinisk epidemiologi,Department of Medical Sciences, Cardiovascular Epidemiology, Uppsala University, Uppsala, Sweden
Sundström, Johan, Professor, 1971- (författare)
Uppsala universitet,Klinisk epidemiologi,Department of Medical Sciences, Clinical Epidemiology, Uppsala University, Uppsala, Sweden; The George Institute for Global Health, Sydney, Australia
Ärnlöv, Johan, 1970- (författare)
Högskolan Dalarna,Medicinsk vetenskap,Karolinska Institutet, Stockholm,Division of and Primary Care, Department of Neurobiology, Care Sciences, and Society, Karolinska Institutet; School of Health and Social Studies, Dalarna University
Berne, Christian (författare)
Uppsala universitet,Molekylär epidemiologi,Science for Life Laboratory, SciLifeLab,Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, EpiHubben, MTC-huset, Uppsala, Sweden
Risérus, Ulf, 1967- (författare)
Uppsala universitet,Klinisk nutrition och metabolism,Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism, Uppsala University, Uppsala, Sweden
Magnusson, Patrik KE (författare)
Karolinska Institutet
Larsson, Susanna C. (författare)
Uppsala universitet,Medicinsk epidemiologi,Unit of Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; Department of Surgical Sciences, Uppsala University, Uppsala, Sweden
Fall, Tove, 1979- (författare)
Uppsala universitet,Science for Life Laboratory, SciLifeLab,Molekylär epidemiologi,Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, EpiHubben, MTC-huset, Uppsala, Sweden
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 (creator_code:org_t)
2021-11-16
2022
Engelska.
Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 71:2, s. 329-339
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https://doi.org/10.2...
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  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
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  • Obesity is associated with adverse health outcomes, but the metabolic effects have not yet been fully elucidated. We aimed to investigate the association between adiposity with circulating metabolites and to address causality with Mendelian randomization (MR). Metabolomics data was generated by non-targeted ultra-performance liquid-chromatography coupled to time-of-flight mass-spectrometry in plasma and serum from three population-based Swedish cohorts: ULSAM (N=1,135), PIVUS (N=970), and TwinGene (N=2,059). We assessed associations between general adiposity measured as body mass index (BMI) and central body fat distribution measured as waist-to-hip ratio adjusted for BMI (WHRadjBMI) with 210 annotated metabolites. We employed MR analysis to assess causal effects. Lastly, we attempted to replicate the MR findings in the KORA and TwinsUK cohorts (N=7,373), the CHARGE consortium (N=8,631), the Framingham Heart Study (N=2,076) and the DIRECT consortium (N=3,029). BMI was associated with 77 metabolites, while WHRadjBMI was associated with 11 and 3 metabolites in women and men, respectively. The MR analyses in the Swedish cohorts suggested a causal association (p-value <0.05) of increased general adiposity and reduced levels of arachidonic acid, dodecanedioic acid and lysophosphatidylcholine (P-16:0) as well as with increased creatine levels. The replication effort provided support for a causal association of adiposity on reduced levels of arachidonic acid (p-value 0.03). Adiposity is associated with variation of large parts of the circulating metabolome, however causality needs further investigation in well-powered cohorts.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)

Nyckelord

Endocrinology
Diabetes and Metabolism
Internal Medicine

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