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Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses.

ABSTRACT: 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.

SUBMITTER: Okbay A

PROVIDER: S-EPMC4884152 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature

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Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses.

Okbay Aysu A Baselmans Bart M L BM De Neve Jan-Emmanuel JE Turley Patrick P Nivard Michel G MG Fontana Mark Alan MA Meddens S Fleur W SF Linnér Richard Karlsson RK Rietveld Cornelius A CA Derringer Jaime J Gratten Jacob J Lee James J JJ Liu Jimmy Z JZ de Vlaming Ronald R Ahluwalia Tarunveer S TS Buchwald Jadwiga J Cavadino Alana A Frazier-Wood Alexis C AC Furlotte Nicholas A NA Garfield Victoria V Geisel Marie Henrike MH Gonzalez Juan R JR Haitjema Saskia S Karlsson Robert R van der Laan Sander W SW Ladwig Karl-Heinz KH Lahti Jari J van der Lee Sven J SJ Lind Penelope A PA Liu Tian T Matteson Lindsay L Mihailov Evelin E Miller Michael B MB Minica Camelia C CC Nolte Ilja M IM Mook-Kanamori Dennis D van der Most Peter J PJ Oldmeadow Christopher C Qian Yong Y Raitakari Olli O Rawal Rajesh R Realo Anu A Rueedi Rico R Schmidt Börge B Smith Albert V AV Stergiakouli Evie E Tanaka Toshiko T Taylor Kent K Thorleifsson Gudmar G Wedenoja Juho J Wellmann Juergen J Westra Harm-Jan HJ Willems Sara M SM Zhao Wei W Amin Najaf N Bakshi Andrew A Bergmann Sven S Bjornsdottir Gyda G Boyle Patricia A PA Cherney Samantha S Cox Simon R SR Davies Gail G Davis Oliver S P OS Ding Jun J Direk Nese N Eibich Peter P Emeny Rebecca T RT Fatemifar Ghazaleh G Faul Jessica D JD Ferrucci Luigi L Ferrucci Luigi L Forstner Andreas J AJ Gieger Christian C Gupta Richa R Harris Tamara B TB Harris Juliette M JM Holliday Elizabeth G EG Hottenga Jouke-Jan JJ De Jager Philip L PL Kaakinen Marika A MA Kajantie Eero E Karhunen Ville V Kolcic Ivana I Kumari Meena M Launer Lenore J LJ Franke Lude L Franke Lude L Li-Gao Ruifang R Liewald David C DC Koini Marisa M Loukola Anu A Marques-Vidal Pedro P Montgomery Grant W GW Mosing Miriam A MA Paternoster Lavinia L Pattie Alison A Petrovic Katja E KE Pulkki-Råback Laura L Quaye Lydia L Räikkönen Katri K Rudan Igor I Rudan Igor I Scott Rodney J RJ Smith Jennifer A JA Sutin Angelina R AR Trzaskowski Maciej M Vinkhuyzen Anna E AE Yu Lei L Zabaneh Delilah D Attia John R JR Bennett David A DA Berger Klaus K Bertram Lars L Boomsma Dorret I DI Snieder Harold H Chang Shun-Chiao SC Cucca Francesco F Deary Ian J IJ van Duijn Cornelia M CM Eriksson Johan G JG Bültmann Ute U de Geus Eco J C EJ Groenen Patrick J F PJ Gudnason Vilmundur V Hansen Torben T Hartman Catharine A CA Haworth Claire M A CM Haworth Claire M A CM Hayward Caroline C Heath Andrew C AC Hinds David A DA Hyppönen Elina E Iacono William G WG Järvelin Marjo-Riitta MR Jöckel Karl-Heinz KH Kaprio Jaakko J Kardia Sharon L R SL Keltikangas-Järvinen Liisa L Kraft Peter P Kubzansky Laura D LD Lehtimäki Terho T Magnusson Patrik K E PK Martin Nicholas G NG McGue Matt M Metspalu Andres A Mills Melinda M de Mutsert Renée R Oldehinkel Albertine J AJ Pasterkamp Gerard G Pedersen Nancy L NL Plomin Robert R Polasek Ozren O Power Christine C Rich Stephen S SS Rosendaal Frits R FR den Ruijter Hester M HM Schlessinger David D Schmidt Helena H Svento Rauli R Schmidt Reinhold R Alizadeh Behrooz Z BZ Sørensen Thorkild I A TI Spector Tim D TD Starr John M JM Stefansson Kari K Steptoe Andrew A Terracciano Antonio A Thorsteinsdottir Unnur U Thurik A Roy AR Timpson Nicholas J NJ Tiemeier Henning H Uitterlinden André G AG Vollenweider Peter P Vollenweider Peter P Wagner Gert G GG Weir David R DR Yang Jian J Conley Dalton C DC Smith George Davey GD Hofman Albert A Johannesson Magnus M Laibson David I DI Medland Sarah E SE Meyer Michelle N MN Pickrell Joseph K JK Esko Tõnu T Krueger Robert F RF Beauchamp Jonathan P JP Koellinger Philipp D PD Benjamin Daniel J DJ Bartels Meike M Cesarini David D

Nature genetics 20160418 6

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 subje ...[more]

PMID: 27089181

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Project description:ObjectiveThe subjective experience of psychotic patients toward treatment is a key factor in medication adherence, quality of life, and clinical outcome. The aim of this study was to assess the subjective well-being in patients with schizophrenia and to examine its relationship with the presence and severity of depressive symptoms.MethodsA multicenter, cross-sectional study was conducted with clinically stable outpatients diagnosed with schizophrenia. The Subjective Well-Being under Neuroleptic Scale - short version (SWN-K) and the Calgary Depression Scale for Schizophrenia (CDSS) were used to gather information on well-being and the presence and severity of depressive symptoms, respectively. Spearman's rank correlation was used to assess the associations between the SWN-K total score, its five subscales, and the CDSS total score. Discriminative validity was evaluated against that criterion by analysing the area under the curve (AUC).ResultsNinety-seven patients were included in the study. Mean age was 35 years (standard deviation = 10) and 72% were male. Both the total SWN-K scale and its five subscales correlated inversely and significantly with the CDSS total score (P < 0.0001). The highest correlation was observed for the total SWN-K (Spearman's rank order correlation [rho] = -0.59), being the other correlations: mental functioning (-0.47), social integration (-0.46), emotional regulation (-0.51), physical functioning (-0.48), and self-control (-0.41). A total of 33 patients (34%) were classified as depressed. Total SWN-K showed the highest AUC when discriminating between depressive severity levels (0.84), followed by emotional regulation (0.80), social integration (0.78), physical functioning and self-control (0.77), and mental functioning (0.73). Total SWN-K and its five subscales showed a significant linear trend against CDSS severity levels (P < 0.001).ConclusionThe presence of moderate to severe depressive symptoms was relatively high, and correlated inversely with patients' subjective well-being. Routine assessment of patient-reported measures in patients with schizophrenia might reduce potential discrepancy between patient and physician assessment, increase therapeutic alliance, and improve outcome.

Project description:Background: Previous observational studies have reported an association between psychiatric traits and cardiovascular diseases (CVDs). In this two-sample Mendelian randomization (MR) study, we aimed to investigate the causality between psychiatric traits and CVDs. Methods: Single-nucleotide polymorphisms (SNPs) associated with autism spectrum disorder (ASD), neuroticism, and subjective well-being at genome-wide significance (P < 1 × 10-8) were identified from genome-wide association studies. Summary-level data of the outcomes, including coronary artery disease (CAD), myocardial infarction (MI), atrial fibrillation (AF), and heart failure (HF), were obtained from several largest datasets. The inverse-variance weighted (IVW) method was used as our main analyses to conduct this MR study. Sensitivity analyses included the weighted median, the MR-robust adjusted profile score (MR-RAPS), and the MR pleiotropy residual sum and outlier (MR-PRESSO) method. Repeated MR analyses using a more relaxed threshold (P < 1 × 10-6) for instruments selection and multivariable MR analyses were also applied to evaluate the robustness of results. Results: The MR analyses showed that genetic predisposition to ASD was associated with a higher risk of AF [odds ratio (OR), 1.109; 95% confidence interval (CI), 1.023-1.201; P = 0.011] and HF (OR, 1.138; 95% CI, 1.036-1.251; P = 0.007). Neuroticism was casually associated with an increased risk of AF (OR, 1.201; 95% CI, 1.037-1.392; P = 0.015), whereas subjective well-being had a protective effect on HF (OR, 0.732; 95% CI, 0.574-0.933; P = 0.012). No other causal association between psychiatric traits and CVDs was observed. Consistent results were obtained in sensitivity analyses. Conclusion: This study provided evidence of causal associations of ASD with a higher risk of AF and HF. Besides, neuroticism was casually associated with an increased risk of AF, and subjective well-being was associated with a decreased risk of HF.

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Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses.

Publications

Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses.

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