%0 Journal Article %J Nat Genet %D 2016 %T Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses. %A Okbay, Aysu %A Baselmans, Bart M L %A De Neve, Jan-Emmanuel %A Turley, Patrick %A Nivard, Michel G %A Mark Alan Fontana %A Meddens, S Fleur W %A Richard Karlsson Linnér %A Cornelius A Rietveld %A Derringer, Jaime %A Gratten, Jacob %A Lee, James J %A Liu, Jimmy Z %A de Vlaming, Ronald %A Ahluwalia, Tarunveer S %A Buchwald, Jadwiga %A Cavadino, Alana %A Frazier-Wood, Alexis C %A Furlotte, Nicholas A %A Garfield, Victoria %A Geisel, Marie Henrike %A Gonzalez, Juan R %A Haitjema, Saskia %A Karlsson, Robert %A van der Laan, Sander W %A Ladwig, Karl-Heinz %A J. Lahti %A Sven J van der Lee %A Penelope A Lind %A Tian Liu %A Lindsay K Matteson %A Mihailov, Evelin %A Michael B Miller %A Minica, Camelia C %A Ilja M Nolte %A Dennis O Mook-Kanamori %A van der Most, Peter J %A Christopher J Oldmeadow %A Qian, Yong %A Olli T Raitakari %A Rawal, Rajesh %A Realo, Anu %A Rueedi, Rico %A Schmidt, Börge %A Albert Vernon Smith %A Stergiakouli, Evie %A Toshiko Tanaka %A Kent D Taylor %A Wedenoja, Juho %A Jürgen Wellmann %A Westra, Harm-Jan %A Willems, Sara M %A Wei Zhao %A Amin, Najaf %A Bakshi, Andrew %A Patricia A. Boyle %A Cherney, Samantha %A Cox, Simon R %A Gail Davies %A Davis, Oliver S P %A Ding, Jun %A Nese Direk %A Eibich, Peter %A Emeny, Rebecca T %A Fatemifar, Ghazaleh %A Jessica Faul %A Luigi Ferrucci %A Andreas J Forstner %A Gieger, Christian %A Gupta, Richa %A Tamara B Harris %A Harris, Juliette M %A Holliday, Elizabeth G %A Jouke-Jan Hottenga %A Philip L de Jager %A Marika A Kaakinen %A Kajantie, Eero %A Karhunen, Ville %A Kolcic, Ivana %A Kumari, Meena %A Lenore J Launer %A Lude L Franke %A Li-Gao, Ruifang %A Koini, Marisa %A Loukola, Anu %A Marques-Vidal, Pedro %A Grant W Montgomery %A Mosing, Miriam A %A Paternoster, Lavinia %A Pattie, Alison %A Katja E Petrovic %A Pulkki-Raback, Laura %A Quaye, Lydia %A Katri Räikkönen %A Rudan, Igor %A Rodney J Scott %A Jennifer A Smith %A Angelina R Sutin %A Trzaskowski, Maciej %A Anna A E Vinkhuyzen %A Lei Yu %A Zabaneh, Delilah %A John R. Attia %A David A Bennett %A Klaus Berger %A Bertram, Lars %A Dorret I Boomsma %A Snieder, Harold %A Chang, Shun-Chiao %A Francesco Cucca %A Ian J Deary %A Cornelia M van Duijn %A Johan G Eriksson %A Bültmann, Ute %A Eco J. C. de Geus %A Groenen, Patrick J F %A Gudnason, Vilmundur %A Hansen, Torben %A Catharina A Hartman %A Haworth, Claire M A %A Caroline Hayward %A Andrew C Heath %A Hinds, David A %A Hyppönen, Elina %A Iacono, William G %A Järvelin, Marjo-Riitta %A Jöckel, Karl-Heinz %A Kaprio, Jaakko %A Sharon L R Kardia %A Keltikangas-Järvinen, Liisa %A Kraft, Peter %A Laura D Kubzansky %A Lehtimäki, Terho %A Patrik K E Magnusson %A Nicholas G Martin %A McGue, Matt %A Andres Metspalu %A Melinda C Mills %A de Mutsert, Renée %A Oldehinkel, Albertine J %A Pasterkamp, Gerard %A Nancy L Pedersen %A Plomin, Robert %A Polasek, Ozren %A Power, Christine %A Rich, Stephen S %A Rosendaal, Frits R %A Hester M. den Ruijter %A Schlessinger, David %A Schmidt, Helena %A Svento, Rauli %A Schmidt, Reinhold %A Alizadeh, Behrooz Z %A Thorkild I. A. Sørensen %A Timothy Spector %A Andrew Steptoe %A Antonio Terracciano %A A. Roy Thurik %A Nicholas J Timpson %A Henning Tiemeier %A André G Uitterlinden %A Vollenweider, Peter %A Wagner, Gert G %A David R Weir %A Yang, Jian %A Dalton C Conley %A Hofman, Albert %A Johannesson, Magnus %A David I Laibson %A Sarah E Medland %A Meyer, Michelle N %A Pickrell, Joseph K %A Tõnu Esko %A Krueger, Robert F %A Jonathan P. Beauchamp %A Philipp D Koellinger %A Daniel J. Benjamin %A Bartels, Meike %A Cesarini, David %K Anxiety Disorders %K Bayes Theorem %K depression %K Genome-Wide Association Study %K Humans %K Neuroticism %K Phenotype %K Polymorphism, Single Nucleotide %X

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.

%B Nat Genet %V 48 %P 624-33 %8 2016 06 %G eng %N 6 %1 http://www.ncbi.nlm.nih.gov/pubmed/27089181?dopt=Abstract %R 10.1038/ng.3552 %0 Journal Article %J Psychol Med %D 2016 %T Somatic, positive and negative domains of the Center for Epidemiological Studies Depression (CES-D) scale: a meta-analysis of genome-wide association studies. %A Demirkan, A %A J. Lahti %A Nese Direk %A Viktorin, A. %A Kathryn L Lunetta %A Antonio Terracciano %A Michael A Nalls %A Toshiko Tanaka %A Karin Hek %A Myriam Fornage %A Jürgen Wellmann %A Marilyn C Cornelis %A Ollila, H. M. %A Lei Yu %A Luke C Pilling %A Isaacs, A %A Aarno Palotie %A Wei Vivian Zhuang %A Alan B Zonderman %A Jessica Faul %A Angelina R Sutin %A Osorio Meirelles %A Mulas, A %A Hofman, A %A André G Uitterlinden %A Fernando Rivadeneira %A Markus Perola %A Wei Zhao %A Veikko Salomaa %A Kristine Yaffe %A Luik, A I %A Yongmei Liu %A Ding, J %A Paul Lichtenstein %A Landén, M %A Elisabeth Widen %A David R Weir %A David J Llewellyn %A Murray, A %A Sharon L R Kardia %A Johan G Eriksson %A Karestan C Koenen %A Patrik K E Magnusson %A Luigi Ferrucci %A Thomas H Mosley %A Francesco Cucca %A Ben A Oostra %A David A Bennett %A Paunio, T. %A Klaus Berger %A Tamara B Harris %A Nancy L Pedersen %A Joanne M Murabito %A Henning Tiemeier %A Cornelia M van Duijn %A Katri Räikkönen %K depression %K Depressive Disorder, Major %K Genome-Wide Association Study %K Humans %K Polymorphism, Single Nucleotide %K Receptor, Melatonin, MT1 %K Somatoform Disorders %X

BACKGROUND: Major depressive disorder (MDD) is moderately heritable, however genome-wide association studies (GWAS) for MDD, as well as for related continuous outcomes, have not shown consistent results. Attempts to elucidate the genetic basis of MDD may be hindered by heterogeneity in diagnosis. The Center for Epidemiological Studies Depression (CES-D) scale provides a widely used tool for measuring depressive symptoms clustered in four different domains which can be combined together into a total score but also can be analysed as separate symptom domains.

METHOD: We performed a meta-analysis of GWAS of the CES-D symptom clusters. We recruited 12 cohorts with the 20- or 10-item CES-D scale (32 528 persons).

RESULTS: One single nucleotide polymorphism (SNP), rs713224, located near the brain-expressed melatonin receptor (MTNR1A) gene, was associated with the somatic complaints domain of depression symptoms, with borderline genome-wide significance (p discovery = 3.82 × 10-8). The SNP was analysed in an additional five cohorts comprising the replication sample (6813 persons). However, the association was not consistent among the replication sample (p discovery+replication = 1.10 × 10-6) with evidence of heterogeneity.

CONCLUSIONS: Despite the effort to harmonize the phenotypes across cohorts and participants, our study is still underpowered to detect consistent association for depression, even by means of symptom classification. On the contrary, the SNP-based heritability and co-heritability estimation results suggest that a very minor part of the variation could be captured by GWAS, explaining the reason of sparse findings.

%B Psychol Med %V 46 %P 1613-23 %8 2016 06 %G eng %U https://www.ncbi.nlm.nih.gov/pubmed/26997408 %N 8 %1 http://www.ncbi.nlm.nih.gov/pubmed/26997408?dopt=Abstract %R 10.1017/S0033291715002081 %0 Journal Article %J Mol Psychiatry %D 2015 %T Genetic contributions to variation in general cognitive function: a meta-analysis of genome-wide association studies in the CHARGE consortium (N=53949). %A Gail Davies %A Armstrong, N. %A Joshua C. Bis %A Bressler, J. %A Chouraki, V. %A Giddaluru, S. %A Edith Hofer %A Carla A Ibrahim-Verbaas %A Kirin, M. %A J. Lahti %A Sven J van der Lee %A Stephanie Le Hellard %A Tian Liu %A Riccardo E Marioni %A Christopher J Oldmeadow %A Postmus, I. %A Albert Vernon Smith %K Aged %K Aged, 80 and over %K Atherosclerosis %K Cognition %K Cognition Disorders %K Cohort Studies %K Female %K Genetic Predisposition to Disease %K Genome-Wide Association Study %K HMGN1 Protein %K Humans %K Male %K Middle Aged %K Neuropsychological tests %K Phenotype %K Polymorphism, Single Nucleotide %K Scotland %X

General cognitive function is substantially heritable across the human life course from adolescence to old age. We investigated the genetic contribution to variation in this important, health- and well-being-related trait in middle-aged and older adults. We conducted a meta-analysis of genome-wide association studies of 31 cohorts (N=53,949) in which the participants had undertaken multiple, diverse cognitive tests. A general cognitive function phenotype was tested for, and created in each cohort by principal component analysis. We report 13 genome-wide significant single-nucleotide polymorphism (SNP) associations in three genomic regions, 6q16.1, 14q12 and 19q13.32 (best SNP and closest gene, respectively: rs10457441, P=3.93 × 10(-9), MIR2113; rs17522122, P=2.55 × 10(-8), AKAP6; rs10119, P=5.67 × 10(-9), APOE/TOMM40). We report one gene-based significant association with the HMGN1 gene located on chromosome 21 (P=1 × 10(-6)). These genes have previously been associated with neuropsychiatric phenotypes. Meta-analysis results are consistent with a polygenic model of inheritance. To estimate SNP-based heritability, the genome-wide complex trait analysis procedure was applied to two large cohorts, the Atherosclerosis Risk in Communities Study (N=6617) and the Health and Retirement Study (N=5976). The proportion of phenotypic variation accounted for by all genotyped common SNPs was 29% (s.e.=5%) and 28% (s.e.=7%), respectively. Using polygenic prediction analysis, ~1.2% of the variance in general cognitive function was predicted in the Generation Scotland cohort (N=5487; P=1.5 × 10(-17)). In hypothesis-driven tests, there was significant association between general cognitive function and four genes previously associated with Alzheimer's disease: TOMM40, APOE, ABCG1 and MEF2C.

%B Mol Psychiatry %I 20 %V 20 %P 183-92 %8 2015 Feb %G eng %N 2 %1 http://www.ncbi.nlm.nih.gov/pubmed/25644384?dopt=Abstract %2 PMC4356746 %4 genetics/genetics/GENOME-WIDE ASSOCIATION/TOMM40/ABCG1/MEF2C/complex train anaysis/Atherosclerosis Risk in Communities Study/cross-national study %$ 999999 %R 10.1038/mp.2014.188 %0 Journal Article %J Science %D 2013 %T GWAS of 126,559 individuals identifies genetic variants associated with educational attainment. %A Cornelius A Rietveld %A Sarah E Medland %A Derringer, Jaime %A Yang, Jian %A Tõnu Esko %A Martin, Nicolas W %A Westra, Harm-Jan %A Shakhbazov, Konstantin %A Abdel Abdellaoui %A Agrawal, Arpana %A Albrecht, Eva %A Alizadeh, Behrooz Z %A Amin, Najaf %A Barnard, John %A Baumeister, Sebastian E %A Benke, Kelly S %A Bielak, Lawrence F %A Boatman, Jeffrey A %A Patricia A. Boyle %A Gail Davies %A Christiaan de Leeuw %A Eklund, Niina %A Daniel S Evans %A Rudolf Ferhmann %A Fischer, Krista %A Gieger, Christian %A Gjessing, Håkon K %A Hägg, Sara %A Harris, Jennifer R %A Caroline Hayward %A Holzapfel, Christina %A Carla A Ibrahim-Verbaas %A Ingelsson, Erik %A Jacobsson, Bo %A Joshi, Peter K %A Jugessur, Astanand %A Marika A Kaakinen %A Kanoni, Stavroula %A Karjalainen, Juha %A Kolcic, Ivana %A Kristiansson, Kati %A Kutalik, Zoltán %A J. Lahti %A Lee, Sang H %A Lin, Peng %A Penelope A Lind %A Yongmei Liu %A Kurt Lohman %A Loitfelder, Marisa %A McMahon, George %A Vidal, Pedro Marques %A Osorio Meirelles %A Lili Milani %A Myhre, Ronny %A Nuotio, Marja-Liisa %A Christopher J Oldmeadow %A Katja E Petrovic %A Wouter J Peyrot %A Polasek, Ozren %A Quaye, Lydia %A Reinmaa, Eva %A Rice, John P %A Rizzi, Thais S %A Schmidt, Helena %A Schmidt, Reinhold %A Albert Vernon Smith %A Jennifer A Smith %A Toshiko Tanaka %A Antonio Terracciano %A van der Loos, Matthijs J H M %A Vitart, Veronique %A Völzke, Henry %A Jürgen Wellmann %A Lei Yu %A Wei Zhao %A Allik, Jüri %A John R. Attia %A Bandinelli, Stefania %A Bastardot, François %A Jonathan P. Beauchamp %A David A Bennett %A Klaus Berger %A Laura Bierut %A Dorret I Boomsma %A Bültmann, Ute %A Campbell, Harry %A Chabris, Christopher F %A Cherkas, Lynn %A Chung, Mina K %A Francesco Cucca %A de Andrade, Mariza %A Philip L de Jager %A De Neve, Jan-Emmanuel %A Ian J Deary %A George Dedoussis %A Deloukas, Panos %A Dimitriou, Maria %A Guðny Eiríksdóttir %A Elderson, Martin F %A Johan G Eriksson %A Jessica Faul %A Luigi Ferrucci %A Melissa E Garcia %A Grönberg, Henrik %A Guðnason, Vilmundur %A Hall, Per %A Harris, Juliette M %A Tamara B Harris %A Nicholas D Hastie %A Andrew C Heath %A Dena G Hernandez %A Hoffmann, Wolfgang %A Hofman, Adriaan %A Holle, Rolf %A Holliday, Elizabeth G %A Jouke-Jan Hottenga %A Iacono, William G %A Illig, Thomas %A Järvelin, Marjo-Riitta %A Kähönen, Mika %A Kaprio, Jaakko %A Kirkpatrick, Robert M %A Kowgier, Matthew %A Latvala, Antti %A Lenore J Launer %A Lawlor, Debbie A %A Lehtimäki, Terho %A Li, Jingmei %A Paul Lichtenstein %A Lichtner, Peter %A David C Liewald %A Pamela A F Madden %A Patrik K E Magnusson %A Mäkinen, Tomi E %A Masala, Marco %A McGue, Matt %A Andres Metspalu %A Mielck, Andreas %A Michael B Miller %A Grant W Montgomery %A Mukherjee, Sutapa %A Nyholt, Dale R %A Ben A Oostra %A Palmer, Lyle J %A Aarno Palotie %A Brenda W J H Penninx %A Markus Perola %A Peyser, Patricia A %A Preisig, Martin %A Katri Räikkönen %A Olli T Raitakari %A Realo, Anu %A Ring, Susan M %A Ripatti, Samuli %A Fernando Rivadeneira %A Rudan, Igor %A Rustichini, Aldo %A Veikko Salomaa %A Sarin, Antti-Pekka %A Schlessinger, David %A Rodney J Scott %A Snieder, Harold %A St Pourcain, Beate %A John M Starr %A Sul, Jae Hoon %A Surakka, Ida %A Svento, Rauli %A Teumer, Alexander %A Henning Tiemeier %A van Rooij, Frank J A %A Van Wagoner, David R %A Vartiainen, Erkki %A Viikari, Jorma %A Vollenweider, Peter %A Vonk, Judith M %A Waeber, Gérard %A David R Weir %A Wichmann, H-Erich %A Elisabeth Widen %A Gonneke Willemsen %A James F Wilson %A Alan F Wright %A Dalton C Conley %A Davey-Smith, George %A Lude L Franke %A Groenen, Patrick J F %A Hofman, Albert %A Johannesson, Magnus %A Sharon L R Kardia %A Krueger, Robert F %A David I Laibson %A Nicholas G Martin %A Meyer, Michelle N %A Posthuma, Danielle %A A. Roy Thurik %A Nicholas J Timpson %A André G Uitterlinden %A Cornelia M van Duijn %A Peter M Visscher %A Daniel J. Benjamin %A Cesarini, David %A Philipp D Koellinger %K Cognition %K Educational Status %K Endophenotypes %K Female %K Genetic Loci %K Genome-Wide Association Study %K Humans %K Male %K Multifactorial Inheritance %K Polymorphism, Single Nucleotide %X

A genome-wide association study (GWAS) of educational attainment was conducted in a discovery sample of 101,069 individuals and a replication sample of 25,490. Three independent single-nucleotide polymorphisms (SNPs) are genome-wide significant (rs9320913, rs11584700, rs4851266), and all three replicate. Estimated effects sizes are small (coefficient of determination R(2) ≈ 0.02%), approximately 1 month of schooling per allele. A linear polygenic score from all measured SNPs accounts for ≈2% of the variance in both educational attainment and cognitive function. Genes in the region of the loci have previously been associated with health, cognitive, and central nervous system phenotypes, and bioinformatics analyses suggest the involvement of the anterior caudate nucleus. These findings provide promising candidate SNPs for follow-up work, and our effect size estimates can anchor power analyses in social-science genetics.

%B Science %V 340 %P 1467-71 %8 2013 Jun 21 %G eng %N 6139 %1 http://www.ncbi.nlm.nih.gov/pubmed/23722424?dopt=Abstract %R 10.1126/science.1235488