IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-39259-x.html
   My bibliography  Save this article

Unravelling the genetic architecture of human complex traits through whole genome sequencing

Author

Listed:
  • Ozvan Bocher

    (Institute of Translational Genomics, Helmholtz Zentrum München, German Research Center for Environmental Health)

  • Cristen J. Willer

    (University of Michigan
    University of Michigan
    University of Michigan)

  • Eleftheria Zeggini

    (Institute of Translational Genomics, Helmholtz Zentrum München, German Research Center for Environmental Health
    Technical University of Munich (TUM) and Klinikum Rechts der Isar, TUM School of Medicine)

Abstract

Whole genome sequencing has enabled new insights into the genetic architecture of complex traits, especially through access to low-frequency and rare variation. This Comment highlights the key contributions from this technology and discusses considerations for its use and future perspectives.

Suggested Citation

  • Ozvan Bocher & Cristen J. Willer & Eleftheria Zeggini, 2023. "Unravelling the genetic architecture of human complex traits through whole genome sequencing," Nature Communications, Nature, vol. 14(1), pages 1-4, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-39259-x
    DOI: 10.1038/s41467-023-39259-x
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-39259-x
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-39259-x?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. Xutong Zhao & Dandi Qiao & Chaojie Yang & Silva Kasela & Wonji Kim & Yanlin Ma & Nick Shrine & Chiara Batini & Tamar Sofer & Sarah A. Gagliano Taliun & Phuwanat Sakornsakolpat & Pallavi P. Balte & Dmi, 2020. "Whole genome sequence analysis of pulmonary function and COPD in 19,996 multi-ethnic participants," Nature Communications, Nature, vol. 11(1), pages 1-12, December.
    2. Jonas B. Nielsen & Oren Rom & Ida Surakka & Sarah E. Graham & Wei Zhou & Tanmoy Roychowdhury & Lars G. Fritsche & Sarah A. Gagliano Taliun & Carlo Sidore & Yuhao Liu & Maiken E. Gabrielsen & Anne Heid, 2020. "Loss-of-function genomic variants highlight potential therapeutic targets for cardiovascular disease," Nature Communications, Nature, vol. 11(1), pages 1-12, December.
    3. Quanli Wang & Ryan S. Dhindsa & Keren Carss & Andrew R. Harper & Abhishek Nag & Ioanna Tachmazidou & Dimitrios Vitsios & Sri V. V. Deevi & Alex Mackay & Daniel Muthas & Michael Hühn & Susan Monkley & , 2021. "Rare variant contribution to human disease in 281,104 UK Biobank exomes," Nature, Nature, vol. 597(7877), pages 527-532, September.
    4. Marcin Kierczak & Nima Rafati & Julia Höglund & Hadrien Gourlé & Valeria Lo Faro & Daniel Schmitz & Weronica E. Ek & Ulf Gyllensten & Stefan Enroth & Diana Ekman & Björn Nystedt & Torgny Karlsson & Ås, 2022. "Contribution of rare whole-genome sequencing variants to plasma protein levels and the missing heritability," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    5. Loïc Yengo & Sailaja Vedantam & Eirini Marouli & Julia Sidorenko & Eric Bartell & Saori Sakaue & Marielisa Graff & Anders U. Eliasen & Yunxuan Jiang & Sridharan Raghavan & Jenkai Miao & Joshua D. Aria, 2022. "A saturated map of common genetic variants associated with human height," Nature, Nature, vol. 610(7933), pages 704-712, October.
    6. Peter Priestley & Jonathan Baber & Martijn P. Lolkema & Neeltje Steeghs & Ewart Bruijn & Charles Shale & Korneel Duyvesteyn & Susan Haidari & Arne Hoeck & Wendy Onstenk & Paul Roepman & Mircea Voda & , 2019. "Pan-cancer whole-genome analyses of metastatic solid tumours," Nature, Nature, vol. 575(7781), pages 210-216, November.
    7. Daniel J. Weiner & Ajay Nadig & Karthik A. Jagadeesh & Kushal K. Dey & Benjamin M. Neale & Elise B. Robinson & Konrad J. Karczewski & Luke J. O’Connor, 2023. "Polygenic architecture of rare coding variation across 394,783 exomes," Nature, Nature, vol. 614(7948), pages 492-499, February.
    8. Margaret Sunitha Selvaraj & Xihao Li & Zilin Li & Akhil Pampana & David Y. Zhang & Joseph Park & Stella Aslibekyan & Joshua C. Bis & Jennifer A. Brody & Brian E. Cade & Lee-Ming Chuang & Ren-Hua Chung, 2022. "Whole genome sequence analysis of blood lipid levels in >66,000 individuals," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    9. Mitja I. Kurki & Juha Karjalainen & Priit Palta & Timo P. Sipilä & Kati Kristiansson & Kati M. Donner & Mary P. Reeve & Hannele Laivuori & Mervi Aavikko & Mari A. Kaunisto & Anu Loukola & Elisa Lahtel, 2023. "Author Correction: FinnGen provides genetic insights from a well-phenotyped isolated population," Nature, Nature, vol. 615(7952), pages 19-19, March.
    10. Julia Steinberg & Lorraine Southam & Theodoros I. Roumeliotis & Matthew J. Clark & Raveen L. Jayasuriya & Diane Swift & Karan M. Shah & Natalie C. Butterfield & Roger A. Brooks & Andrew W. McCaskie & , 2021. "A molecular quantitative trait locus map for osteoarthritis," Nature Communications, Nature, vol. 12(1), pages 1-11, December.
    11. Daniel Taliun & Daniel N. Harris & Michael D. Kessler & Jedidiah Carlson & Zachary A. Szpiech & Raul Torres & Sarah A. Gagliano Taliun & André Corvelo & Stephanie M. Gogarten & Hyun Min Kang & Achille, 2021. "Sequencing of 53,831 diverse genomes from the NHLBI TOPMed Program," Nature, Nature, vol. 590(7845), pages 290-299, February.
    12. Mitja I. Kurki & Juha Karjalainen & Priit Palta & Timo P. Sipilä & Kati Kristiansson & Kati M. Donner & Mary P. Reeve & Hannele Laivuori & Mervi Aavikko & Mari A. Kaunisto & Anu Loukola & Elisa Lahtel, 2023. "FinnGen provides genetic insights from a well-phenotyped isolated population," Nature, Nature, vol. 613(7944), pages 508-518, January.
    Full references (including those not matched with items on IDEAS)

    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. 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.
    2. Matthew Tegtmeyer & Jatin Arora & Samira Asgari & Beth A. Cimini & Ajay Nadig & Emily Peirent & Dhara Liyanage & Gregory P. Way & Erin Weisbart & Aparna Nathan & Tiffany Amariuta & Kevin Eggan & Marzi, 2024. "High-dimensional phenotyping to define the genetic basis of cellular morphology," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    3. Tuomo Hartonen & Bradley Jermy & Hanna Sõnajalg & Pekka Vartiainen & Kristi Krebs & Andrius Vabalas & Tuija Leino & Hanna Nohynek & Jonas Sivelä & Reedik Mägi & Mark Daly & Hanna M. Ollila & Lili Mila, 2023. "Nationwide health, socio-economic and genetic predictors of COVID-19 vaccination status in Finland," Nature Human Behaviour, Nature, vol. 7(7), pages 1069-1083, July.
    4. William R. Reay & Dylan J. Kiltschewskij & Maria A. Biase & Zachary F. Gerring & Kousik Kundu & Praveen Surendran & Laura A. Greco & Erin D. Clarke & Clare E. Collins & Alison M. Mondul & Demetrius Al, 2024. "Genetic influences on circulating retinol and its relationship to human health," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    5. Linda Ottensmann & Rubina Tabassum & Sanni E. Ruotsalainen & Mathias J. Gerl & Christian Klose & Elisabeth Widén & Kai Simons & Samuli Ripatti & Matti Pirinen, 2023. "Genome-wide association analysis of plasma lipidome identifies 495 genetic associations," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    6. Hui Chen & Zeyang Wang & Lihai Gong & Qixuan Wang & Wenyan Chen & Jia Wang & Xuelian Ma & Ruofan Ding & Xing Li & Xudong Zou & Mireya Plass & Cheng Lian & Ting Ni & Gong-Hong Wei & Wei Li & Lin Deng &, 2024. "A distinct class of pan-cancer susceptibility genes revealed by an alternative polyadenylation transcriptome-wide association study," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    7. Aoxing Liu & Evelina T. Akimova & Xuejie Ding & Sakari Jukarainen & Pekka Vartiainen & Tuomo Kiiskinen & Sara Koskelainen & Aki S. Havulinna & Mika Gissler & Stefano Lombardi & Tove Fall & Melinda C. , 2024. "Evidence from Finland and Sweden on the relationship between early-life diseases and lifetime childlessness in men and women," Nature Human Behaviour, Nature, vol. 8(2), pages 276-287, February.
    8. Jiwoo Lee & Sakari Jukarainen & Antti Karvanen & Padraig Dixon & Neil M. Davies & George Davey Smith & Pradeep Natarajan & Andrea Ganna, 2023. "Quantifying the causal impact of biological risk factors on healthcare costs," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    9. Anders Mälarstig & Felix Grassmann & Leo Dahl & Marios Dimitriou & Dianna McLeod & Marike Gabrielson & Karl Smith-Byrne & Cecilia E. Thomas & Tzu-Hsuan Huang & Simon K. G. Forsberg & Per Eriksson & Mi, 2023. "Evaluation of circulating plasma proteins in breast cancer using Mendelian randomisation," Nature Communications, Nature, vol. 14(1), pages 1-9, December.
    10. Alexander T. Williams & Jing Chen & Kayesha Coley & Chiara Batini & Abril Izquierdo & Richard Packer & Erik Abner & Stavroula Kanoni & David J. Shepherd & Robert C. Free & Edward J. Hollox & Nigel J. , 2023. "Genome-wide association study of thyroid-stimulating hormone highlights new genes, pathways and associations with thyroid disease," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    11. Mischan Vali-Pour & Solip Park & Jose Espinosa-Carrasco & Daniel Ortiz-Martínez & Ben Lehner & Fran Supek, 2022. "The impact of rare germline variants on human somatic mutation processes," Nature Communications, Nature, vol. 13(1), pages 1-21, December.
    12. 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.
    13. Cambrosio, Alberto & Campbell, Jonah & Keating, Peter & Polk, Jessica B. & Aguilar-Mahecha, Adriana & Basik, Mark, 2022. "Healthcare policy by other means: Cancer clinical research as “oncopolicy”," Social Science & Medicine, Elsevier, vol. 292(C).
    14. Mathias Seviiri & Matthew H. Law & Jue-Sheng Ong & Puya Gharahkhani & Pierre Fontanillas & Catherine M. Olsen & David C. Whiteman & Stuart MacGregor, 2022. "A multi-phenotype analysis reveals 19 susceptibility loci for basal cell carcinoma and 15 for squamous cell carcinoma," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    15. Elena V. Feofanova & Michael R. Brown & Taryn Alkis & Astrid M. Manuel & Xihao Li & Usman A. Tahir & Zilin Li & Kevin M. Mendez & Rachel S. Kelly & Qibin Qi & Han Chen & Martin G. Larson & Rozenn N. L, 2023. "Whole-Genome Sequencing Analysis of Human Metabolome in Multi-Ethnic Populations," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    16. Xiaoyi Raymond Gao & Marion Chiariglione & Alexander J. Arch, 2022. "Whole-exome sequencing study identifies rare variants and genes associated with intraocular pressure and glaucoma," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    17. 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.
    18. Xingjie Hao & Zhonghe Shao & Ning Zhang & Minghui Jiang & Xi Cao & Si Li & Yunlong Guan & Chaolong Wang, 2023. "Integrative genome-wide analyses identify novel loci associated with kidney stones and provide insights into its genetic architecture," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    19. Pei-Kuan Cong & Wei-Yang Bai & Jin-Chen Li & Meng-Yuan Yang & Saber Khederzadeh & Si-Rui Gai & Nan Li & Yu-Heng Liu & Shi-Hui Yu & Wei-Wei Zhao & Jun-Quan Liu & Yi Sun & Xiao-Wei Zhu & Pian-Pian Zhao , 2022. "Genomic analyses of 10,376 individuals in the Westlake BioBank for Chinese (WBBC) pilot project," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    20. Nazia Pathan & Wei Q. Deng & Matteo Di Scipio & Mohammad Khan & Shihong Mao & Robert W. Morton & Ricky Lali & Marie Pigeyre & Michael R. Chong & Guillaume Paré, 2024. "A method to estimate the contribution of rare coding variants to complex trait heritability," Nature Communications, Nature, vol. 15(1), pages 1-16, 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:14:y:2023:i:1:d:10.1038_s41467-023-39259-x. 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.