IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v12y2021i1d10.1038_s41467-021-26970-w.html
   My bibliography  Save this article

Simultaneous estimation of bi-directional causal effects and heritable confounding from GWAS summary statistics

Author

Listed:
  • Liza Darrous

    (University Center for Primary Care and Public Health, University of Lausanne
    Swiss Institute of Bioinformatics)

  • Ninon Mounier

    (University Center for Primary Care and Public Health, University of Lausanne
    Swiss Institute of Bioinformatics)

  • Zoltán Kutalik

    (University Center for Primary Care and Public Health, University of Lausanne
    Swiss Institute of Bioinformatics
    University of Lausanne)

Abstract

Mendelian Randomisation (MR) is an increasingly popular approach that estimates the causal effect of risk factors on complex human traits. While it has seen several extensions that relax its basic assumptions, most suffer from two major limitations; their under-exploitation of genome-wide markers, and sensitivity to the presence of a heritable confounder of the exposure-outcome relationship. To overcome these limitations, we propose a Latent Heritable Confounder MR (LHC-MR) method applicable to association summary statistics, which estimates bi-directional causal effects, direct heritabilities, and confounder effects while accounting for sample overlap. We demonstrate that LHC-MR outperforms several existing MR methods in a wide range of simulation settings and apply it to summary statistics of 13 complex traits. Besides several concordant results with other MR methods, LHC-MR unravels new mechanisms (how disease diagnosis might lead to improved lifestyle) and reveals new causal effects (e.g. HDL cholesterol being protective against high systolic blood pressure), hidden from standard MR methods due to a heritable confounder of opposite effect direction.

Suggested Citation

  • Liza Darrous & Ninon Mounier & Zoltán Kutalik, 2021. "Simultaneous estimation of bi-directional causal effects and heritable confounding from GWAS summary statistics," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
  • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-26970-w
    DOI: 10.1038/s41467-021-26970-w
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-021-26970-w
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-021-26970-w?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. Duncan Thomas & John Strauss & Maria-Helena Henriques, 1991. "How Does Mother's Education Affect Child Height?," Journal of Human Resources, University of Wisconsin Press, vol. 26(2), pages 183-211.
    2. Cawley, John & Markowitz, Sara & Tauras, John, 2004. "Lighting up and slimming down: the effects of body weight and cigarette prices on adolescent smoking initiation," Journal of Health Economics, Elsevier, vol. 23(2), pages 293-311, March.
    3. Eleanor Sanderson & George Davey Smith & Jack Bowden & Marcus R. Munafò, 2019. "Mendelian randomisation analysis of the effect of educational attainment and cognitive ability on smoking behaviour," Nature Communications, Nature, vol. 10(1), pages 1-9, December.
    4. Benson, Rebecca & von Hippel, Paul T. & Lynch, Jamie L., 2018. "Does more education cause lower BMI, or do lower-BMI individuals become more educated? Evidence from the National Longitudinal Survey of Youth 1979," Social Science & Medicine, Elsevier, vol. 211(C), pages 370-377.
    5. Richard Howey & So-Youn Shin & Caroline Relton & George Davey Smith & Heather J Cordell, 2020. "Bayesian network analysis incorporating genetic anchors complements conventional Mendelian randomization approaches for exploratory analysis of causal relationships in complex data," PLOS Genetics, Public Library of Science, vol. 16(3), pages 1-35, March.
    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. Liza Darrous & Gibran Hemani & George Davey Smith & Zoltán Kutalik, 2024. "PheWAS-based clustering of Mendelian Randomisation instruments reveals distinct mechanism-specific causal effects between obesity and educational attainment," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    2. Jennifer Sjaarda & Zoltán Kutalik, 2023. "Partner choice, confounding and trait convergence all contribute to phenotypic partner similarity," Nature Human Behaviour, Nature, vol. 7(5), pages 776-789, May.

    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. Jennifer M. Mellor, 2011. "Do cigarette taxes affect children's body mass index? The effect of household environment on health," Health Economics, John Wiley & Sons, Ltd., vol. 20(4), pages 417-431, April.
    2. Skoufias, Emmanuel, 1998. "Determinants of child health during the economic transition in Romania," World Development, Elsevier, vol. 26(11), pages 2045-2056, November.
    3. Ahsan, Md Nazmul & Maharaj, Riddhi, 2018. "Parental human capital and child health at birth in India," Economics & Human Biology, Elsevier, vol. 30(C), pages 130-149.
    4. Tom Coupé & W. Robert Reed, 2021. "Do Negative Replications Affect Citations?," Working Papers in Economics 21/14, University of Canterbury, Department of Economics and Finance.
    5. Fitzsimons, Emla & Malde, Bansi & Mesnard, Alice & Vera-Hernández, Marcos, 2016. "Nutrition, information and household behavior: Experimental evidence from Malawi," Journal of Development Economics, Elsevier, vol. 122(C), pages 113-126.
    6. Djankov, Simeon & McLiesh, Caralee & Nenova, Tatiana & Shleifer, Andrei, 2003. "Who Owns the Media?," Journal of Law and Economics, University of Chicago Press, vol. 46(2), pages 341-381, October.
    7. Sun, Ang & Zhao, Yaohui, 2016. "Divorce, abortion, and the child sex ratio: The impact of divorce reform in China," Journal of Development Economics, Elsevier, vol. 120(C), pages 53-69.
    8. Sanchez, Alan & Jaramillo, Miguel, 2012. "Impacto del programa Juntos sobre la nutrición temprana," Revista Estudios Económicos, Banco Central de Reserva del Perú, issue 23, pages 53-66.
    9. Gilles Postel‐Vinay & David E. Sahn, 2010. "Explaining stunting in nineteenth‐century France," Economic History Review, Economic History Society, vol. 63(2), pages 315-334, May.
    10. Vani Borooah & Sriya Iyer, 2005. "Vidya, Veda, and Varna: The influence of religion and caste on education in rural India," Journal of Development Studies, Taylor & Francis Journals, vol. 41(8), pages 1369-1404.
    11. Le, Dung D. & Molina, Teresa & Ibuka, Yoko & Goto, Rei, 2024. "The Intergenerational Health Effects of Child Marriage Bans," IZA Discussion Papers 17089, Institute of Labor Economics (IZA).
    12. Subha Mani, 2012. "Is there Complete, Partial, or No Recovery from Childhood Malnutrition? – Empirical Evidence from Indonesia," Oxford Bulletin of Economics and Statistics, Department of Economics, University of Oxford, vol. 74(5), pages 691-715, October.
    13. Arne Bigsten & Jörgen Levin, 2001. "Growth, Income Distribution, and Poverty," WIDER Working Paper Series DP2001-129, World Institute for Development Economic Research (UNU-WIDER).
    14. Aysit Tansel & Ceyhan Ozturk & Erkan Erdil, 2021. "The Impact of Body Mass Index on Growth, Schooling, Productivity, and Savings: A Cross-Country Study," Koç University-TUSIAD Economic Research Forum Working Papers 2118, Koc University-TUSIAD Economic Research Forum.
    15. Deniz Karaoğlan & Dürdane Şirin Saraçoğlu, 2018. "Socio-Economic Factors Affecting Early Childhood Health: the Case of Turkey," Child Indicators Research, Springer;The International Society of Child Indicators (ISCI), vol. 11(3), pages 1051-1075, June.
    16. Thao Bui, 2023. "Compulsory education reform and child mortality in Peru," Health Economics, John Wiley & Sons, Ltd., vol. 32(9), pages 1941-1963, September.
    17. Hui Zheng & Jonathan Dirlam & Paola Echave, 2021. "Divergent Trends in the Effects of Early Life Factors on Adult Health," Population Research and Policy Review, Springer;Southern Demographic Association (SDA), vol. 40(5), pages 1119-1148, October.
    18. Karimi, Seyed M. & Basu, Anirban, 2018. "The effect of prenatal exposure to Ramadan on children’s height," Economics & Human Biology, Elsevier, vol. 30(C), pages 69-83.
    19. Gibson, John, 2001. "Literacy and Intrahousehold Externalities," World Development, Elsevier, vol. 29(1), pages 155-166, January.
    20. Jungho Kim, 2010. "Women's Education and Fertility: An Analysis of the Relationship between Education and Birth Spacing in Indonesia," Economic Development and Cultural Change, University of Chicago Press, vol. 58(4), pages 739-774, July.

    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:12:y:2021:i:1:d:10.1038_s41467-021-26970-w. 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.