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Winkler, Thomas W. ; Günther, Felix ; Höllerer, Simon ; Zimmermann, Martina ; Loos, Ruth J. F. ; Kutalik, Zoltán ; Heid, Iris M.

A joint view on genetic variants for adiposity differentiates subtypes with distinct metabolic implications

Winkler, Thomas W. , Günther, Felix, Höllerer, Simon, Zimmermann, Martina , Loos, Ruth J. F. , Kutalik, Zoltán und Heid, Iris M. (2018) A joint view on genetic variants for adiposity differentiates subtypes with distinct metabolic implications. Nature Communications 9 (1946), S. 1-13.

Veröffentlichungsdatum dieses Volltextes: 22 Apr 2021 13:59
Artikel
DOI zum Zitieren dieses Dokuments: 10.5283/epub.37428


Zusammenfassung

The problem of the genetics of related phenotypes is often addressed by analyzing adjusted-model traits, but such traits warrant cautious interpretation. Here, we adopt a joint view of adiposity traits in similar to 322,154 subjects (GIANT consortium). We classify 159 signals associated with body mass index (BMI), waist-to-hip ratio (WHR), or WHR adjusted for BMI (WHRadjBMI) at P < 5 x 10(-8), ...

The problem of the genetics of related phenotypes is often addressed by analyzing adjusted-model traits, but such traits warrant cautious interpretation. Here, we adopt a joint view of adiposity traits in similar to 322,154 subjects (GIANT consortium). We classify 159 signals associated with body mass index (BMI), waist-to-hip ratio (WHR), or WHR adjusted for BMI (WHRadjBMI) at P < 5 x 10(-8), into four classes based on the direction of their effects on BMI and WHR. Our classes help differentiate adiposity genetics with respect to anthropometry, fat depots, and metabolic health. Class-specific Mendelian randomization reveals that variants associated with both WHR-decrease and BMI increase are linked to metabolically rather favorable adiposity through beneficial hip fat. Class-specific enrichment analyses implicate digestive systems as a pathway in adiposity genetics. Our results demonstrate that WHRadjBMI variants capture relevant effects of "unexpected fat distribution given the BMI" and that a joint view of the genetics underlying related phenotypes can inform on important biology.



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Details

DokumentenartArtikel
Titel eines Journals oder einer ZeitschriftNature Communications
Verlag:Nature
Ort der Veröffentlichung:LONDON
Band:9
Nummer des Zeitschriftenheftes oder des Kapitels:1946
Seitenbereich:S. 1-13
Datum16 Mai 2018
InstitutionenMedizin > Institut für Epidemiologie und Präventivmedizin > Lehrstuhl für Genetische Epidemiologie
Identifikationsnummer
WertTyp
10.1038/s41467-018-04124-9DOI
Stichwörter / KeywordsGENOME-WIDE ASSOCIATION; BODY-MASS INDEX; FAT; TISSUE; RISK; ARCHITECTURE; METAANALYSIS; INSIGHTS; DISEASE; BIOLOGY;
Dewey-Dezimal-Klassifikation500 Naturwissenschaften und Mathematik > 570 Biowissenschaften, Biologie
StatusVeröffentlicht
BegutachtetJa, diese Version wurde begutachtet
An der Universität Regensburg entstandenJa
URN der UB Regensburgurn:nbn:de:bvb:355-epub-374281
Dokumenten-ID37428

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