IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-30931-2.html
   My bibliography  Save this article

Inherited basis of visceral, abdominal subcutaneous and gluteofemoral fat depots

Author

Listed:
  • Saaket Agrawal

    (Broad Institute of MIT and Harvard
    Massachusetts General Hospital
    Harvard Medical School)

  • Minxian Wang

    (Broad Institute of MIT and Harvard
    Massachusetts General Hospital
    Beijing Institute of Genomics, Chinese Academy of Sciences)

  • Marcus D. R. Klarqvist

    (Broad Institute of MIT and Harvard)

  • Kirk Smith

    (Broad Institute of MIT and Harvard
    Massachusetts General Hospital
    Harvard Medical School)

  • Joseph Shin

    (Broad Institute of MIT and Harvard
    Massachusetts General Hospital)

  • Hesam Dashti

    (Broad Institute of MIT and Harvard)

  • Nathaniel Diamant

    (Broad Institute of MIT and Harvard)

  • Seung Hoan Choi

    (Broad Institute of MIT and Harvard
    Massachusetts General Hospital)

  • Sean J. Jurgens

    (Broad Institute of MIT and Harvard
    Massachusetts General Hospital
    Amsterdam UMC, University of Amsterdam)

  • Patrick T. Ellinor

    (Broad Institute of MIT and Harvard
    Massachusetts General Hospital
    Harvard Medical School)

  • Anthony Philippakis

    (Broad Institute of MIT and Harvard
    Broad Institute of MIT and Harvard)

  • Melina Claussnitzer

    (Broad Institute of MIT and Harvard
    Massachusetts General Hospital
    Harvard Medical School)

  • Kenney Ng

    (Center for Computational Health, IBM Research)

  • Miriam S. Udler

    (Broad Institute of MIT and Harvard
    Massachusetts General Hospital
    Harvard Medical School)

  • Puneet Batra

    (Broad Institute of MIT and Harvard)

  • Amit V. Khera

    (Broad Institute of MIT and Harvard
    Massachusetts General Hospital
    Harvard Medical School
    Verve Therapeutics)

Abstract

For any given level of overall adiposity, individuals vary considerably in fat distribution. The inherited basis of fat distribution in the general population is not fully understood. Here, we study up to 38,965 UK Biobank participants with MRI-derived visceral (VAT), abdominal subcutaneous (ASAT), and gluteofemoral (GFAT) adipose tissue volumes. Because these fat depot volumes are highly correlated with BMI, we additionally study six local adiposity traits: VAT adjusted for BMI and height (VATadj), ASATadj, GFATadj, VAT/ASAT, VAT/GFAT, and ASAT/GFAT. We identify 250 independent common variants (39 newly-identified) associated with at least one trait, with many associations more pronounced in female participants. Rare variant association studies extend prior evidence for PDE3B as an important modulator of fat distribution. Local adiposity traits (1) highlight depot-specific genetic architecture and (2) enable construction of depot-specific polygenic scores that have divergent associations with type 2 diabetes and coronary artery disease. These results – using MRI-derived, BMI-independent measures of local adiposity – confirm fat distribution as a highly heritable trait with important implications for cardiometabolic health outcomes.

Suggested Citation

  • Saaket Agrawal & Minxian Wang & Marcus D. R. Klarqvist & Kirk Smith & Joseph Shin & Hesam Dashti & Nathaniel Diamant & Seung Hoan Choi & Sean J. Jurgens & Patrick T. Ellinor & Anthony Philippakis & Me, 2022. "Inherited basis of visceral, abdominal subcutaneous and gluteofemoral fat depots," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-30931-2
    DOI: 10.1038/s41467-022-30931-2
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-30931-2
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-022-30931-2?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Clare Bycroft & Colin Freeman & Desislava Petkova & Gavin Band & Lloyd T. Elliott & Kevin Sharp & Allan Motyer & Damjan Vukcevic & Olivier Delaneau & Jared O’Connell & Adrian Cortes & Samantha Welsh &, 2018. "The UK Biobank resource with deep phenotyping and genomic data," Nature, Nature, vol. 562(7726), pages 203-209, October.
    2. Thomas J. Littlejohns & Jo Holliday & Lorna M. Gibson & Steve Garratt & Niels Oesingmann & Fidel Alfaro-Almagro & Jimmy D. Bell & Chris Boultwood & Rory Collins & Megan C. Conroy & Nicola Crabtree & N, 2020. "The UK Biobank imaging enhancement of 100,000 participants: rationale, data collection, management and future directions," Nature Communications, Nature, vol. 11(1), pages 1-12, December.
    3. Adam E. Locke & Bratati Kahali & Sonja I. Berndt & Anne E. Justice & Tune H. Pers & Felix R. Day & Corey Powell & Sailaja Vedantam & Martin L. Buchkovich & Jian Yang & Damien C. Croteau-Chonka & Tonu , 2015. "Genetic studies of body mass index yield new insights for obesity biology," Nature, Nature, vol. 518(7538), pages 197-206, February.
    4. Jean-Pierre Després & Isabelle Lemieux, 2006. "Abdominal obesity and metabolic syndrome," Nature, Nature, vol. 444(7121), pages 881-887, December.
    5. Nellie Y. Loh & James E. N. Minchin & Katherine E. Pinnick & Manu Verma & Marijana Todorčević & Nathan Denton & Julia El-Sayed Moustafa & John P. Kemp & Celia L. Gregson & David M. Evans & Matt J. Nev, 2020. "RSPO3 impacts body fat distribution and regulates adipose cell biology in vitro," Nature Communications, Nature, vol. 11(1), pages 1-15, December.
    6. Konrad J. Karczewski & Laurent C. Francioli & Grace Tiao & Beryl B. Cummings & Jessica Alföldi & Qingbo Wang & Ryan L. Collins & Kristen M. Laricchia & Andrea Ganna & Daniel P. Birnbaum & Laura D. Gau, 2020. "The mutational constraint spectrum quantified from variation in 141,456 humans," Nature, Nature, vol. 581(7809), pages 434-443, May.
    7. Tune H. Pers & Juha M. Karjalainen & Yingleong Chan & Harm-Jan Westra & Andrew R. Wood & Jian Yang & Julian C. Lui & Sailaja Vedantam & Stefan Gustafsson & Tonu Esko & Tim Frayling & Elizabeth K. Spel, 2015. "Biological interpretation of genome-wide association studies using predicted gene functions," Nature Communications, Nature, vol. 6(1), pages 1-9, May.
    8. Janina S. Ried & Janina Jeff M. & Audrey Y. Chu & Jennifer L. Bragg-Gresham & Jenny van Dongen & Jennifer E. Huffman & Tarunveer S. Ahluwalia & Gemma Cadby & Niina Eklund & Joel Eriksson & Tõnu Esko &, 2016. "A principal component meta-analysis on multiple anthropometric traits identifies novel loci for body shape," Nature Communications, Nature, vol. 7(1), pages 1-11, December.
    9. Ron Do & Nathan O. Stitziel & Hong-Hee Won & Anders Berg Jørgensen & Stefano Duga & Pier Angelica Merlini & Adam Kiezun & Martin Farrall & Anuj Goel & Or Zuk & Illaria Guella & Rosanna Asselta & Lesli, 2015. "Exome sequencing identifies rare LDLR and APOA5 alleles conferring risk for myocardial infarction," Nature, Nature, vol. 518(7537), pages 102-106, February.
    10. Dmitry Shungin & Thomas W. Winkler & Damien C. Croteau-Chonka & Teresa Ferreira & Adam E. Locke & Reedik Mägi & Rona J. Strawbridge & Tune H. Pers & Krista Fischer & Anne E. Justice & Tsegaselassie Wo, 2015. "New genetic loci link adipose and insulin biology to body fat distribution," Nature, Nature, vol. 518(7538), pages 187-196, February.
    Full references (including those not matched with items on IDEAS)

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Saaket Agrawal & Marcus D. R. Klarqvist & Nathaniel Diamant & Takara L. Stanley & Patrick T. Ellinor & Nehal N. Mehta & Anthony Philippakis & Kenney Ng & Melina Claussnitzer & Steven K. Grinspoon & Pu, 2023. "BMI-adjusted adipose tissue volumes exhibit depot-specific and divergent associations with cardiometabolic diseases," Nature Communications, Nature, vol. 14(1), pages 1-10, December.

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Parsa Akbari & Olukayode A. Sosina & Jonas Bovijn & Karl Landheer & Jonas B. Nielsen & Minhee Kim & Senem Aykul & Tanima De & Mary E. Haas & George Hindy & Nan Lin & Ian R. Dinsmore & Jonathan Z. Luo , 2022. "Multiancestry exome sequencing reveals INHBE mutations associated with favorable fat distribution and protection from diabetes," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    2. Andrew D. Grotzinger & Travis T. Mallard & Zhaowen Liu & Jakob Seidlitz & Tian Ge & Jordan W. Smoller, 2023. "Multivariate genomic architecture of cortical thickness and surface area at multiple levels of analysis," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    3. Jacob Joseph & Chang Liu & Qin Hui & Krishna Aragam & Zeyuan Wang & Brian Charest & Jennifer E. Huffman & Jacob M. Keaton & Todd L. Edwards & Serkalem Demissie & Luc Djousse & Juan P. Casas & J. Micha, 2022. "Genetic architecture of heart failure with preserved versus reduced ejection fraction," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    4. Saaket Agrawal & Marcus D. R. Klarqvist & Nathaniel Diamant & Takara L. Stanley & Patrick T. Ellinor & Nehal N. Mehta & Anthony Philippakis & Kenney Ng & Melina Claussnitzer & Steven K. Grinspoon & Pu, 2023. "BMI-adjusted adipose tissue volumes exhibit depot-specific and divergent associations with cardiometabolic diseases," Nature Communications, Nature, vol. 14(1), pages 1-10, December.
    5. Lili Liu & Atlas Khan & Elena Sanchez-Rodriguez & Francesca Zanoni & Yifu Li & Nicholas Steers & Olivia Balderes & Junying Zhang & Priya Krithivasan & Robert A. LeDesma & Clara Fischman & Scott J. Heb, 2022. "Genetic regulation of serum IgA levels and susceptibility to common immune, infectious, kidney, and cardio-metabolic traits," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    6. Aimee M. Deaton & Aditi Dubey & Lucas D. Ward & Peter Dornbos & Jason Flannick & Elaine Yee & Simina Ticau & Leila Noetzli & Margaret M. Parker & Rachel A. Hoffing & Carissa Willis & Mollie E. Plekan , 2022. "Rare loss of function variants in the hepatokine gene INHBE protect from abdominal obesity," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    7. Young Jin Kim & Sanghoon Moon & Mi Yeong Hwang & Sohee Han & Hye-Mi Jang & Jinhwa Kong & Dong Mun Shin & Kyungheon Yoon & Sung Min Kim & Jong-Eun Lee & Anubha Mahajan & Hyun-Young Park & Mark I. McCar, 2022. "The contribution of common and rare genetic variants to variation in metabolic traits in 288,137 East Asians," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    8. Hazewinkel, Audinga-Dea & Richmond, Rebecca C. & Wade, Kaitlin H. & Dixon, Padraig, 2022. "Mendelian randomization analysis of the causal impact of body mass index and waist-hip ratio on rates of hospital admission," Economics & Human Biology, Elsevier, vol. 44(C).
    9. Vincent Michaud & Eulalie Lasseaux & David J. Green & Dave T. Gerrard & Claudio Plaisant & Tomas Fitzgerald & Ewan Birney & Benoît Arveiler & Graeme C. Black & Panagiotis I. Sergouniotis, 2022. "The contribution of common regulatory and protein-coding TYR variants to the genetic architecture of albinism," Nature Communications, Nature, vol. 13(1), pages 1-8, December.
    10. Nicole Deflaux & Margaret Sunitha Selvaraj & Henry Robert Condon & Kelsey Mayo & Sara Haidermota & Melissa A. Basford & Chris Lunt & Anthony A. Philippakis & Dan M. Roden & Joshua C. Denny & Anjene Mu, 2023. "Demonstrating paths for unlocking the value of cloud genomics through cross cohort analysis," Nature Communications, Nature, vol. 14(1), pages 1-10, December.
    11. Cecilia Pessoa Rodrigues & Aindrila Chatterjee & Meike Wiese & Thomas Stehle & Witold Szymanski & Maria Shvedunova & Asifa Akhtar, 2021. "Histone H4 lysine 16 acetylation controls central carbon metabolism and diet-induced obesity in mice," Nature Communications, Nature, vol. 12(1), pages 1-21, December.
    12. Ruoyu Tian & Tian Ge & Hyeokmoon Kweon & Daniel B. Rocha & Max Lam & Jimmy Z. Liu & Kritika Singh & Daniel F. Levey & Joel Gelernter & Murray B. Stein & Ellen A. Tsai & Hailiang Huang & Christopher F., 2024. "Whole-exome sequencing in UK Biobank reveals rare genetic architecture for depression," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    13. Magdalena Zimoń & Yunfeng Huang & Anthi Trasta & Aliaksandr Halavatyi & Jimmy Z. Liu & Chia-Yen Chen & Peter Blattmann & Bernd Klaus & Christopher D. Whelan & David Sexton & Sally John & Wolfgang Hube, 2021. "Pairwise effects between lipid GWAS genes modulate lipid plasma levels and cellular uptake," Nature Communications, Nature, vol. 12(1), pages 1-16, December.
    14. Catherine M. Francis & Matthias E. Futschik & Jian Huang & Wenjia Bai & Muralidharan Sargurupremraj & Alexander Teumer & Monique M. B. Breteler & Enrico Petretto & Amanda S. R. Ho & Philippe Amouyel &, 2022. "Genome-wide associations of aortic distensibility suggest causality for aortic aneurysms and brain white matter hyperintensities," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    15. H. Serhat Tetikol & Deniz Turgut & Kubra Narci & Gungor Budak & Ozem Kalay & Elif Arslan & Sinem Demirkaya-Budak & Alexey Dolgoborodov & Duygu Kabakci-Zorlu & Vladimir Semenyuk & Amit Jain & Brandi N., 2022. "Pan-African genome demonstrates how population-specific genome graphs improve high-throughput sequencing data analysis," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    16. Milton Pividori & Sumei Lu & Binglan Li & Chun Su & Matthew E. Johnson & Wei-Qi Wei & Qiping Feng & Bahram Namjou & Krzysztof Kiryluk & Iftikhar J. Kullo & Yuan Luo & Blair D. Sullivan & Benjamin F. V, 2023. "Projecting genetic associations through gene expression patterns highlights disease etiology and drug mechanisms," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    17. Jeffrey D. Wall & J. Fah Sathirapongsasuti & Ravi Gupta & Asif Rasheed & Radha Venkatesan & Saurabh Belsare & Ramesh Menon & Sameer Phalke & Anuradha Mittal & John Fang & Deepak Tanneeru & Manjari Des, 2023. "South Asian medical cohorts reveal strong founder effects and high rates of homozygosity," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    18. Ada J. S. Chan & Worrawat Engchuan & Miriam S. Reuter & Zhuozhi Wang & Bhooma Thiruvahindrapuram & Brett Trost & Thomas Nalpathamkalam & Carol Negrijn & Sylvia Lamoureux & Giovanna Pellecchia & Rohan , 2022. "Genome-wide rare variant score associates with morphological subtypes of autism spectrum disorder," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    19. Andrew D. Grotzinger & Javier de la Fuente & Gail Davies & Michel G. Nivard & Elliot M. Tucker-Drob, 2022. "Transcriptome-wide and stratified genomic structural equation modeling identify neurobiological pathways shared across diverse cognitive traits," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    20. Stephanie O. Erjavec & Sahar Gelfman & Alexa R. Abdelaziz & Eunice Y. Lee & Isha Monga & Anna Alkelai & Iuliana Ionita-Laza & Lynn Petukhova & Angela M. Christiano, 2022. "Whole exome sequencing in Alopecia Areata identifies rare variants in KRT82," Nature Communications, Nature, vol. 13(1), pages 1-13, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-30931-2. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.