Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses
Open accessAbstract
Very few genetic variants have been associated with depression and neuroticism, likely because of limitations on sample size in previous studies. Subjective well-being, a phenotype that is genetically correlated with both of these traits, has not yet been studied with genome-wide data. We conducted genome-wide association studies of three phenotypes: subjective well-being (n = 298,420), depressive symptoms (n = 161,460), and neuroticism (n = 170,911). We identify 3 variants associated with subjective well-being, 2 variants associated with depressive symptoms, and 11 variants associated with neuroticism, including 2 inversion polymorphisms. The two loci associated with depressive symptoms replicate in an independent depression sample. Joint analyses that exploit the high genetic correlations between the phenotypes (|ρ^| ≈ 0.8) strengthen the overall credibility of the findings and allow us to identify additional variants. Across our phenotypes, loci regulating expression in central nervous system and adrenal or pancreas tissues are strongly enriched for association.
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There is a genetic overlap between MDD and other psychiatric disorders.
“there is a genetic overlap between MDD and other psychiatric disorders 46,47”
From Major depressive disorder (2016) · cites this paper as [47]
The Biological analyses section (page unavailable) reports genetic correlations between depressive symptoms and schizophrenia, bipolar disorder, and anxiety disorders. That supports genetic overlap involving depressive symptoms, but the paper's own estimates do not establish the claim specifically for diagnosed MDD. (LLM, conf=0.86)
Experimental — accuracy not yet measuredOf eight phenotypes evaluated, only cognitive phenotypes showed strong heterogeneity across ASD subgroups (educational attainment P=1.8 x 10^-8, IQ P=3.7 x 10^-9).
“Of the eight phenotypes we evaluated, only the cognitive phenotypes showed strong heterogeneity (educational attainment 20 P = 1.8 x 10 -8 , IQ 23 P = 3.7 x 10 -9 )”
From Identification of common genetic risk variants for autism spectrum disorder (2019) · cites this paper as [23]
The Abstract reports GWAS of subjective well-being, depressive symptoms, and neuroticism, while Biological analyses discusses genetic correlations with autism spectrum disorder. Our copy does not report educational-attainment or IQ heterogeneity across ASD subgroups or either quoted P value (searched: educational attainment, IQ, ASD subgroups, and both P values). The heterogeneity result is also phrased as the citing authors’ own evaluation, rather than a finding attributed to this source. (LLM, conf=0.76)
Experimental — accuracy not yet measuredOverlap with neuroticism studies highlighted putative depression associations for DRD2, CELF4, and ELAVL2.
“Examining significant genes that overlap between the current meta-analysis of depression and the neuroticism studies of both Luciano, et al. 18 and Okbay, et al. 19 revealed putative associations with DRD2, CUGBP Elav-like family member 4 (CELF4) and ELAV like RNA binding protein 2 (ELAVL2).”
From Genome-wide meta-analysis of depression identifies 102 independent variants and highlights the importance of the prefrontal brain regions (2019) · cites this paper as [19]
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- Authors
- Study, L. C., Okbay, A., Baselmans, B. M. L., De Neve, J.-E., Turley, P., Nivard, M. G., Fontana, M. A., Meddens, S. F. W., Linnér, R. K., Rietveld, C. A., Derringer, J., Gratten, J., Lee, J. J., Liu, J. Z., de Vlaming, R., Ahluwalia, T. S., Buchwald, J., Cavadino, A., Frazier-Wood, A. C., Furlotte, N. A., Garfield, V., Geisel, M. H., Gonzalez, J. R., Haitjema, S., Karlsson, R., van der Laan, S. W., Ladwig, K.-H., Lahti, J., van der Lee, S. J., Lind, P. A., Liu, T., Matteson, L., Mihailov, E., Miller, M. B., Minica, C. C., Nolte, I. M., Mook-Kanamori, D., van der Most, P. J., Oldmeadow, C., Qian, Y., Raitakari, O., Rawal, R., Realo, A., Rueedi, R., Schmidt, B., Smith, A. V., Stergiakouli, E., Tanaka, T., Taylor, K., Thorleifsson, G., Wedenoja, J., Wellmann, J., Westra, H.-J., Willems, S. M., Zhao, W., Amin, N., Bakshi, A., Bergmann, S., Bjornsdottir, G., Boyle, P. A., Cherney, S., Cox, S. R., Davies, G., Davis, O. S. P., Ding, J., Direk, N., Eibich, P., Emeny, R. T., Fatemifar, G., Faul, J. D., Ferrucci, L., Forstner, A. J., Gieger, C., Gupta, R., Harris, T. B., Harris, J. M., Holliday, E. G., Hottenga, J.-J., De Jager, P. L., Kaakinen, M. A., Kajantie, E., Karhunen, V., Kolcic, I., Kumari, M., Launer, L. J., Franke, L., Li-Gao, R., Liewald, D. C., Koini, M., Loukola, A., Marques-Vidal, P., Montgomery, G. W., Mosing, M. A., Paternoster, L., Pattie, A., Petrovic, K. E., Pulkki-Råback, L., Quaye, L., Räikkönen, K., Rudan, I., Scott, R. J., Smith, J. A., Sutin, A. R., Trzaskowski, M., Vinkhuyzen, A. E., Yu, L., Zabaneh, D., Attia, J. R., Bennett, D. A., Berger, K., Bertram, L., Boomsma, D. I., Snieder, H., Chang, S.-C., Cucca, F., Deary, I. J., van Duijn, C. M., Eriksson, J. G., Bültmann, U., de Geus, E. J. C., Groenen, P. J. F., Gudnason, V., Hansen, T., Hartman, C. A., Haworth, C. M. A., Hayward, C., Heath, A. C., Hinds, D. A., Hyppönen, E., Iacono, W. G., Järvelin, M.-R., Jöckel, K.-H., Kaprio, J., Kardia, S. L. R., Keltikangas-Järvinen, L., Kraft, P., Kubzansky, L. D., Lehtimäki, T., Magnusson, P. K. E., Martin, N. G., McGue, M., Metspalu, A., Mills, M., de Mutsert, R., Oldehinkel, A. J., Pasterkamp, G., Pedersen, N. L., Plomin, R., Polasek, O., Power, C., Rich, S. S., Rosendaal, F. R., den Ruijter, H. M., Schlessinger, D., Schmidt, H., Svento, R., Schmidt, R., Alizadeh, B. Z., Sørensen, T. I. A., Spector, T. D., Starr, J. M., Stefansson, K., Steptoe, A., Terracciano, A., Thorsteinsdottir, U., Thurik, A. R., Timpson, N. J., Tiemeier, H., Uitterlinden, A. G., Vollenweider, P., Wagner, G. G., Weir, D. R., Yang, J., Conley, D. C., Smith, G. D., Hofman, A., Johannesson, M., Laibson, D. I., Medland, S. E., Meyer, M. N., Pickrell, J. K., Esko, T., Krueger, R. F., Beauchamp, J. P., Koellinger, P. D., Benjamin, D. J., Bartels, M., & Cesarini, D.
- Affiliations
- University Medical Center Groningen (NL)
- Erasmus MC (NL)
- University of Oxford (GB)
- Harvard University (US)
- University of Southern California (US)
- Vrije Universiteit Amsterdam (NL)
- University of Illinois Urbana-Champaign (US)
- University of Minnesota (US)
- University of Copenhagen (DK)
- University of Helsinki (FI)
- Queen Mary University of London (GB)
- 23andMe (United States) (US)
- Essen University Hospital (DE)
- Center for Research in Environmental Epidemiology (ES)
- Karolinska Institutet (SE)
- QIMR Berghofer Medical Research Institute (AU)
- Hunter Medical Research Institute (AU)
- University of Turku (FI)
- Helmholtz Munich (DE)
- University of Warwick (GB)
- SIB Swiss Institute of Bioinformatics (CH)
- University of Iceland (IS)
- National Institutes of Health (US)
- deCODE Genetics (Iceland) (IS)
- Brigham and Women's Hospital (US)
- University of Michigan (US)
- The University of Queensland (AU)
- Rush University Medical Center (US)
- RAND Corporation (US)
- University of Edinburgh (GB)
- University of Bristol (GB)
- German Institute for Economic Research (DE)
- Dartmouth College (US)
- University of Bonn (DE)
- King's College London (GB)
- Oulu University Hospital (FI)
- Medical University of Graz (AT)
- University of Newcastle Australia (AU)
- Florida State University (US)
- University of Münster (DE)
- Institute for Integrative and Experimental Genomics (DE)
- Institute of Genetic and Biomedical Research (IT)
- Icelandic Heart Association (IS)
- Washington University in St. Louis (US)
- Tampere University (FI)
- Leiden University Medical Center (NL)
- University Medical Center Utrecht (NL)
- South Australian Health and Medical Research Institute (AU)
- University of Graz (AT)
- Translational Research Institute (AU)
- Princeton University (US)
- Clarkson University (US)
- New York Genome Center (US)
- Amsterdam Neuroscience (NL)
- New York University (US)
- Corresponding author
- Koellinger, Philipp D
- Benjamin, Daniel J
- Bartels, Meike
- ORCID
- Okbay, Aysu
- Baselmans, Bart M L
- Turley, Patrick
- Nivard, Michel G
- Meddens, S Fleur W
- Linnér, Richard Karlsson
- Rietveld, Cornelius A
- Derringer, Jaime
- Gratten, Jacob
- Lee, James J
- Liu, Jimmy Z
- Ahluwalia, Tarunveer S
- Buchwald, Jadwiga
- Cavadino, Alana
- Garfield, Victoria
- Haitjema, Saskia
- Karlsson, Robert
- Lahti, Jari
- van der Lee, Sven J
- Lind, Penelope A
- Miller, Michael B
- Nolte, Ilja M
- van der Most, Peter J
- Oldmeadow, Christopher
- Raitakari, Olli
- Realo, Anu
- Rueedi, Rico
- Smith, Albert V
- Stergiakouli, Evie
- Taylor, Kent
- Wedenoja, Juho
- Westra, Harm-Jan
- Zhao, Wei
- Amin, Najaf
- Bakshi, Andrew
- Boyle, Patricia A
- Davis, Oliver S P
- Ding, Jun
- Eibich, Peter
- Emeny, Rebecca T
- Fatemifar, Ghazaleh
- Faul, Jessica D
- Ferrucci, Luigi
- Forstner, Andreas J
- Gieger, Christian
- Gupta, Richa
- Harris, Tamara B
- Harris, Juliette M
- Hottenga, Jouke-Jan
- Kaakinen, Marika A
- Kajantie, Eero
- Karhunen, Ville
- Launer, Lenore J
- Franke, Lude
- Liewald, David C
- Loukola, Anu
- Marques-Vidal, Pedro
- Montgomery, Grant W
- Mosing, Miriam A
- Paternoster, Lavinia
- Räikkönen, Katri
- Rudan, Igor
- Scott, Rodney J
- Smith, Jennifer A
- Sutin, Angelina R
- Trzaskowski, Maciej
- Yu, Lei
- Zabaneh, Delilah
- Attia, John R
- Boomsma, Dorret I
- Snieder, Harold
- Cucca, Francesco
- Deary, Ian J
- Eriksson, Johan G
- Bültmann, Ute
- de Geus, Eco J C
- Groenen, Patrick J F
- Gudnason, Vilmundur
- Hansen, Torben
- Haworth, Claire M A
- Hayward, Caroline
- Heath, Andrew C
- Hinds, David A
- Hyppönen, Elina
- Iacono, William G
- Järvelin, Marjo-Riitta
- Kaprio, Jaakko
- Kardia, Sharon L R
- Kraft, Peter
- Kubzansky, Laura D
- Lehtimäki, Terho
- Magnusson, Patrik K E
- Martin, Nicholas G
- McGue, Matt
- Metspalu, Andres
- Oldehinkel, Albertine J
- Pasterkamp, Gerard
- Pedersen, Nancy L
- Plomin, Robert
- Power, Christine
- Rich, Stephen S
- Rosendaal, Frits R
- Schlessinger, David
- Schmidt, Helena
- Svento, Rauli
- Schmidt, Reinhold
- Alizadeh, Behrooz Z
- Spector, Tim D
- Starr, John M
- Steptoe, Andrew
- Terracciano, Antonio
- Timpson, Nicholas J
- Tiemeier, Henning
- Uitterlinden, André G
- Wagner, Gert G
- Weir, David R
- Yang, Jian
- Smith, George Davey
- Johannesson, Magnus
- Laibson, David I
- Medland, Sarah E
- Esko, Tõnu
- Beauchamp, Jonathan P
- Koellinger, Philipp D
- Benjamin, Daniel J
- Bartels, Meike
- Cesarini, David
- Venue
- Nature Genetics
- Published
- 2016-04-18
- Volume
- 48
- Issue
- 6
- Pages
- 624-633
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- PMC
- PMC4884152
- OpenAlex
- W2336993262
- Semantic Scholar
- e3e819b6d88696aac80a64623435df2b34d82b3e
- Cited by
- 1,013
- References
- 54
- Citations by year
- 2026: 38 · 2025: 73 · 2024: 73 · 2023: 91 · 2022: 97 · 2021: 115 · 2020: 137 · 2019: 142 · 2018: 112 · 2017: 99 · 2016: 36
- FWCI
- 104.64
- Type
- journal article
- Language
- en
- Update notices
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- UniSA Research Outputs Repository (University of South Australia) (acceptedVersion)
- Open Access at Essex (University of Essex) (acceptedVersion)
- Bristol Research (University of Bristol) (acceptedVersion, other-oa)
- Adelaide Research & Scholarship (AR&S) (University of Adelaide) (submittedVersion, other-oa)
- IRIS (submittedVersion, other-oa)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- RePEc: Research Papers in Economics (submittedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
- RePub (Erasmus University Rotterdam) (submittedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- HAL (submittedVersion)
- Leiden Repository (Leiden University) (submittedVersion)
- Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
- eScholarship (California Digital Library) (submittedVersion)
- Max Planck Digital Library (submittedVersion)
- UnissResearch (Università degli Studi di Sassari) (submittedVersion)
- Research Portal (King's College London) (submittedVersion, other-oa)
- Site cant be reached (submittedVersion)
- Pure Amsterdam UMC (submittedVersion, cc-by)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- PuSH - Publication Server of Helmholtz Zentrum München (submittedVersion)
- Explore Bristol Research (submittedVersion, other-oa)
- VU Research Portal (submittedVersion)
- SERVAL (Université de Lausanne) (submittedVersion, other-oa)
- Spiral (Imperial College London) (submittedVersion)
- STM:n Hallinnonalan avoin julkaisuarkisto (Julkari) (submittedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
- Utrecht University Repository (Utrecht University) (submittedVersion)
- NOVA (University of Newcastle Australia) (submittedVersion)
- WOS
- ERIM Top-Core Articles
- Funders
- National Science Foundation
- University of Southern California
- Wellcome Trust (202802/Z/16/Z)
- National Institute for Health and Care Research (NF-SI-0507-10228, NF-SI-0514-10027)
- Vetenskapsrådet (421-2013-1061)
- Novo Nordisk Fonden (NNF15OC0016362, NNF12OC1016374)
- National Institutes of Health (UL1TR000124)
- Medical Research Council (MR/N01104X/1, MR/J012165/1, MR/K026992/1, MC_PC_15018)
- Economic and Social Research Council (ES/N011856/1, ES/K005774/1, 1336609, ES/M010341/1)
- National Institute on Aging (R01AG017917, ZIAAG000675, R01AG015819, P30AG010161, T32AG000186, AG005842, RF1AG015819, R01AG042568, R03AG051960, P01AG005842, P30AG012810, U01AG009740)
- National Institute on Drug Abuse (R01DA036216, R37DA005147)
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK063491)
- Office of Behavioral and Social Sciences Research
- National Center for Advancing Translational Sciences
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (P2CHD047879)
- H2020 European Research Council (647648)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Mapping and Diversity in Plants and Animals
- Keywords
- subjective well-being, depressive symptoms, neuroticism, genetic variants, genetic correlation, inversion polymorphism, depression genetics, gene expression regulation, central nervous system, adrenal tissue
- MeSH terms
- Neuroticism, Anxiety Disorders, Bayes Theorem, Depression, Humans, Phenotype, Polymorphism, Single Nucleotide, Genome-Wide Association Study
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
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