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Interaction between the FTO gene, body mass index and depression: meta-analysis of 13701 individuals
- Margarita Rivera, Adam E. Locke, Tanguy Corre, Darina Czamara, Christiane Wolf, Ana Ching-Lopez, Yuri Milaneschi, Stefan Kloiber, Sara Cohen-Woods, James Rucker, Katherine J. Aitchison, Sven Bergmann, Dorret I. Boomsma, Nick Craddock, Michael Gill, Florian Holsboer, Jouke-Jan Hottenga, Ania Korszun, Zoltan Kutalik, Susanne Lucae, Wolfgang Maier, Ole Mors, Bertram Müller-Myhsok, Michael J. Owen, Brenda W. J. H. Penninx, Martin Preisig, John Rice, Marcella Rietschel, Federica Tozzi, Rudolf Uher, Peter Vollenweider, Gerard Waeber, Gonneke Willemsen, Ian W. Craig, Anne E. Farmer, Cathryn M. Lewis, Gerome Breen, Peter McGuffin
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- Journal:
- The British Journal of Psychiatry / Volume 211 / Issue 2 / August 2017
- Published online by Cambridge University Press:
- 02 January 2018, pp. 70-76
- Print publication:
- August 2017
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Background
Depression and obesity are highly prevalent, and major impacts on public health frequently co-occur. Recently, we reported that having depression moderates the effect of the FTO gene, suggesting its implication in the association between depression and obesity.
AimsTo confirm these findings by investigating the FTO polymorphism rs9939609 in new cohorts, and subsequently in a meta-analysis.
MethodThe sample consists of 6902 individuals with depression and 6799 controls from three replication cohorts and two original discovery cohorts. Linear regression models were performed to test for association between rs9939609 and body mass index (BMI), and for the interaction between rs9939609 and depression status for an effect on BMI. Fixed and random effects meta-analyses were performed using METASOFT.
ResultsIn the replication cohorts, we observed a significant interaction between FTO, BMI and depression with fixed effects meta-analysis (β=0.12, P = 2.7 × 10−4) and with the Han/Eskin random effects method (P = 1.4 × 10−7) but not with traditional random effects (β = 0.1, P = 0.35). When combined with the discovery cohorts, random effects meta-analysis also supports the interaction (β = 0.12, P = 0.027) being highly significant based on the Han/Eskin model (P = 6.9 × 10−8). On average, carriers of the risk allele who have depression have a 2.2% higher BMI for each risk allele, over and above the main effect of FTO.
ConclusionsThis meta-analysis provides additional support for a significant interaction between FTO, depression and BMI, indicating that depression increases the effect of FTO on BMI. The findings provide a useful starting point in understanding the biological mechanism involved in the association between obesity and depression.
Polygenic interactions with environmental adversity in the aetiology of major depressive disorder
- N. Mullins, R. A. Power, H. L. Fisher, K. B. Hanscombe, J. Euesden, R. Iniesta, D. F. Levinson, M. M. Weissman, J. B. Potash, J. Shi, R. Uher, S. Cohen-Woods, M. Rivera, L. Jones, I. Jones, N. Craddock, M. J. Owen, A. Korszun, I. W. Craig, A. E. Farmer, P. McGuffin, G. Breen, C. M. Lewis
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- Journal:
- Psychological Medicine / Volume 46 / Issue 4 / March 2016
- Published online by Cambridge University Press:
- 03 November 2015, pp. 759-770
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Background
Major depressive disorder (MDD) is a common and disabling condition with well-established heritability and environmental risk factors. Gene–environment interaction studies in MDD have typically investigated candidate genes, though the disorder is known to be highly polygenic. This study aims to test for interaction between polygenic risk and stressful life events (SLEs) or childhood trauma (CT) in the aetiology of MDD.
MethodThe RADIANT UK sample consists of 1605 MDD cases and 1064 controls with SLE data, and a subset of 240 cases and 272 controls with CT data. Polygenic risk scores (PRS) were constructed using results from a mega-analysis on MDD by the Psychiatric Genomics Consortium. PRS and environmental factors were tested for association with case/control status and for interaction between them.
ResultsPRS significantly predicted depression, explaining 1.1% of variance in phenotype (p = 1.9 × 10−6). SLEs and CT were also associated with MDD status (p = 2.19 × 10−4 and p = 5.12 × 10−20, respectively). No interactions were found between PRS and SLEs. Significant PRSxCT interactions were found (p = 0.002), but showed an inverse association with MDD status, as cases who experienced more severe CT tended to have a lower PRS than other cases or controls. This relationship between PRS and CT was not observed in independent replication samples.
ConclusionsCT is a strong risk factor for MDD but may have greater effect in individuals with lower genetic liability for the disorder. Including environmental risk along with genetics is important in studying the aetiology of MDD and PRS provide a useful approach to investigating gene–environment interactions in complex traits.
Familiality and SNP heritability of age at onset and episodicity in major depressive disorder
- P. Ferentinos, A. Koukounari, R. Power, M. Rivera, R. Uher, N. Craddock, M. J. Owen, A. Korszun, L. Jones, I. Jones, M. Gill, J. P. Rice, M. Ising, W. Maier, O. Mors, M. Rietschel, M. Preisig, E. B. Binder, K. J. Aitchison, J. Mendlewicz, D. Souery, J. Hauser, N. Henigsberg, G. Breen, I. W. Craig, A. E. Farmer, B. Müller-Myhsok, P. McGuffin, C. M. Lewis
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- Journal:
- Psychological Medicine / Volume 45 / Issue 10 / July 2015
- Published online by Cambridge University Press:
- 20 February 2015, pp. 2215-2225
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Background
Strategies to dissect phenotypic and genetic heterogeneity of major depressive disorder (MDD) have mainly relied on subphenotypes, such as age at onset (AAO) and recurrence/episodicity. Yet, evidence on whether these subphenotypes are familial or heritable is scarce. The aims of this study are to investigate the familiality of AAO and episode frequency in MDD and to assess the proportion of their variance explained by common single nucleotide polymorphisms (SNP heritability).
MethodFor investigating familiality, we used 691 families with 2–5 full siblings with recurrent MDD from the DeNt study. We fitted (square root) AAO and episode count in a linear and a negative binomial mixed model, respectively, with family as random effect and adjusting for sex, age and center. The strength of familiality was assessed with intraclass correlation coefficients (ICC). For estimating SNP heritabilities, we used 3468 unrelated MDD cases from the RADIANT and GSK Munich studies. After similarly adjusting for covariates, derived residuals were used with the GREML method in GCTA (genome-wide complex trait analysis) software.
ResultsSignificant familial clustering was found for both AAO (ICC = 0.28) and episodicity (ICC = 0.07). We calculated from respective ICC estimates the maximal additive heritability of AAO (0.56) and episodicity (0.15). SNP heritability of AAO was 0.17 (p = 0.04); analysis was underpowered for calculating SNP heritability of episodicity.
ConclusionsAAO and episodicity aggregate in families to a moderate and small degree, respectively. AAO is under stronger additive genetic control than episodicity. Larger samples are needed to calculate the SNP heritability of episodicity. The described statistical framework could be useful in future analyses.
Use of vitamin D supplements during infancy in an international feeding trial
- Eveliina Lehtonen, Anne Ormisson, Anita Nucci, David Cuthbertson, Susa Sorkio, Mila Hyytinen, Kirsi Alahuhta, Carol Berseth, Marja Salonen, Shayne Taback, Margaret Franciscus, Teba González-Frutos, Tuuli E Korhonen, Margaret L Lawson, Dorothy J Becker, Jeffrey P Krischer, Mikael Knip, Suvi M Virtanen, , Thomas Mandrup-Poulsen, Elias Arjas, Åke Lernmark, Barbara Schmidt, Jeffrey P. Krischer, Hans K. Åkerblom, Mila Hyytinen, Mikael Knip, Katriina Koski, Matti Koski, Eeva Pajakkala, Marja Salonen, David Cuthbertson, Jeffrey P. Krischer, Linda Shanker, Brenda Bradley, Hans-Michael Dosch, John Dupré, William Fraser, Margaret Lawson, Jeffrey L. Mahon, Mathew Sermer, Shayne P. Taback, Dorothy Becker, Margaret Franciscus, Anita Nucci, Jerry Palmer, Minna Pekkala, Suvi M. Virtanen, Jacki Catteau, Neville Howard, Patricia Crock, Maria Craig, Cheril L. Clarson, Lynda Bere, David Thompson, Daniel Metzger, Colleen Marshall, Jennifer Kwan, David K. Stephure, Daniele Pacaud, Wendy Schwarz, Rose Girgis, Marilyn Thompson, Shayne P. Taback, Daniel Catte, Margaret L. Lawson, Brenda Bradley, Denis Daneman, Mathew Sermer, Mary-Jean Martin, Valérie Morin, Lyne Frenette, Suzanne Ferland, Susan Sanderson, Kathy Heath, Céline Huot, Monique Gonthier, Maryse Thibeault, Laurent Legault, Diane Laforte, Elizabeth A. Cummings, Karen Scott, Tracey Bridger, Cheryl Crummell, Robyn Houlden, Adriana Breen, George Carson, Sheila Kelly, Koravangattu Sankaran, Marie Penner, Richard A. White, Nancy King, James Popkin, Laurie Robson, Eva Al Taji, Irena Aldhoon, Pavla Mendlova, Jan Vavrinec, Jan Vosahlo, Ludmila Brazdova, Jitrenka Venhacova, Petra Venhacova, Adam Cipra, Zdenka Tomsikova, Petra Krckova, Pavla Gogelova, Ülle Einberg, Mall-Anne Riikjärv, Anne Ormisson, Vallo Tillmann, Päivi Kleemola, Anna Parkkola, Heli Suomalainen, Anna-Liisa Järvenpää, Anu-Maaria Hämälainen, Hannu Haavisto, Sirpa Tenhola, Pentti Lautala, Pia Salonen, Susanna Aspholm, Heli Siljander, Carita Holm, Samuli Ylitalo, Raisa Lounamaa, Anja Nuuja, Timo Talvitie, Kaija Lindström, Hanna Huopio, Jouni Pesola, Riitta Veijola, Päivi Tapanainen, Abram Alar, Paavo Korpela, Marja-Liisa Käär, Taina Mustila, Ritva Virransalo, Päivi Nykänen, Bärbel Aschemeier, Thomas Danne, Olga Kordonouri, Dóra Krikovszky, László Madácsy, Yeganeh Manon Khazrai, Ernesto Maddaloni, Paolo Pozzilli, Carla Mannu, Marco Songini, Carine de Beaufort, Ulrike Schierloh, Jan Bruining, Margriet Bisschoff, Aleksander Basiak, Renata Wasikowa, Marta Ciechanowska, Grazyna Deja, Przemyslawa Jarosz-Chobot, Agnieszka Szadkowska, Katarzyna Cypryk, Malgorzata Zawodniak-Szalapska, Luis Castano, Teba Gonzalez Frutos, Mirentxu Oyarzabal, Manuel Serrano-Ríos, María Teresa Martínez-Larrad, Federico Gustavo Hawkins, Dolores Rodriguez Arnau, Johnny Ludvigsson, Malgorzata Smolinska Konefal, Ragnar Hanas, Bengt Lindblad, Nils-Osten Nilsson, Hans Fors, Maria Nordwall, Agne Lindh, Hans Edenwall, Jan Aman, Calle Johansson, Margrit Gadient, Eugen Schoenle, Dorothy Becker, Ashi Daftary, Margaret Franciscus, Carol Gilmour, Jerry Palmer, Rachel Taculad, Marilyn Tanner-Blasiar, Neil White, Uday Devaskar, Heather Horowitz, Lisa Rogers, Roxana Colon, Teresa Frazer, Jose Torres, Robin Goland, Ellen Greenberg, Maudene Nelson, Holly Schachner, Barney Softness, Jorma Ilonen, Massimo Trucco, Lynn Nichol, Erkki Savilahti, Taina Härkönen, Mikael Knip, Outi Vaarala, Kristiina Luopajärvi, Hans-Michael Dosch
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- Journal:
- Public Health Nutrition / Volume 17 / Issue 4 / April 2014
- Published online by Cambridge University Press:
- 24 June 2013, pp. 810-822
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Objective
To examine the use of vitamin D supplements during infancy among the participants in an international infant feeding trial.
DesignLongitudinal study.
SettingInformation about vitamin D supplementation was collected through a validated FFQ at the age of 2 weeks and monthly between the ages of 1 month and 6 months.
SubjectsInfants (n 2159) with a biological family member affected by type 1 diabetes and with increased human leucocyte antigen-conferred susceptibility to type 1 diabetes from twelve European countries, the USA, Canada and Australia.
ResultsDaily use of vitamin D supplements was common during the first 6 months of life in Northern and Central Europe (>80 % of the infants), with somewhat lower rates observed in Southern Europe (>60 %). In Canada, vitamin D supplementation was more common among exclusively breast-fed than other infants (e.g. 71 % v. 44 % at 6 months of age). Less than 2 % of infants in the USA and Australia received any vitamin D supplementation. Higher gestational age, older maternal age and longer maternal education were study-wide associated with greater use of vitamin D supplements.
ConclusionsMost of the infants received vitamin D supplements during the first 6 months of life in the European countries, whereas in Canada only half and in the USA and Australia very few were given supplementation.
Estimating the heritability of reporting stressful life events captured by common genetic variants
- R. A. Power, T. Wingenbach, S. Cohen-Woods, R. Uher, M. Y. Ng, A. W. Butler, M. Ising, N. Craddock, M. J. Owen, A. Korszun, L. Jones, I. Jones, M. Gill, J. P. Rice, W. Maier, A. Zobel, O. Mors, A. Placentino, M. Rietschel, S. Lucae, F. Holsboer, E. B. Binder, R. Keers, F. Tozzi, P. Muglia, G. Breen, I. W. Craig, B. Müller-Myhsok, J. L. Kennedy, J. Strauss, J. B. Vincent, C. M. Lewis, A. E. Farmer, P. McGuffin
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- Journal:
- Psychological Medicine / Volume 43 / Issue 9 / September 2013
- Published online by Cambridge University Press:
- 14 December 2012, pp. 1965-1971
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Background
Although usually thought of as external environmental stressors, a significant heritable component has been reported for measures of stressful life events (SLEs) in twin studies.
MethodWe examined the variance in SLEs captured by common genetic variants from a genome-wide association study (GWAS) of 2578 individuals. Genome-wide complex trait analysis (GCTA) was used to estimate the phenotypic variance tagged by single nucleotide polymorphisms (SNPs). We also performed a GWAS on the number of SLEs, and looked at correlations between siblings.
ResultsA significant proportion of variance in SLEs was captured by SNPs (30%, p = 0.04). When events were divided into those considered to be dependent or independent, an equal amount of variance was explained for both. This ‘heritability’ was in part confounded by personality measures of neuroticism and psychoticism. A GWAS for the total number of SLEs revealed one SNP that reached genome-wide significance (p = 4 × 10−8), although this association was not replicated in separate samples. Using available sibling data for 744 individuals, we also found a significant positive correlation of R2 = 0.08 in SLEs (p = 0.03).
ConclusionsThese results provide independent validation from molecular data for the heritability of reporting environmental measures, and show that this heritability is in part due to both common variants and the confounding effect of personality.
Standards Development for the Characterization of Quantum Dot Suspensions and Solids
- Lynn Davis, Seth Coe-Sullivan, Oleg Shchekin, K.C. Mishra, Madis Raukas, Rohit Modi, Craig Breen, Mike Leibowitz
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- Journal:
- MRS Online Proceedings Library Archive / Volume 1207 / 2009
- Published online by Cambridge University Press:
- 31 January 2011, 1207-N04-09
- Print publication:
- 2009
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Luminescent nanoparticles such as quantum dots (QDs) are beginning to appear in SSL devices and other commercial products. The allure of QDs in SSL these applications is the potential to provide enhanced device performance (e.g., improved energy efficiency, better color rendering properties, etc.) than is possible with conventional technologies. When used in SSL and other applications, QDs are typically incorporated into or coated onto a solid organic or inorganic matrix and then are excited using external stimuli (e.g., blue light with a maximum wavelength of 450 nm). This structure is vastly different from the colloidal environment in which QDs are typically synthesized and characterized. Bridging the gap between the measurements typically acquired by QD providers and those needed by potential end-users is currently difficult due to the absence of agreed upon standard test methods. Measurements taken in colloidal QD suspensions often do not translate to solid-phase material characterizations due to a variety of factors including sample preparation methods (e.g., temperature, solvents, etc), QD concentrations, and effects arising from the presence of the solid matrix. Additionally, solid samples are more likely to exhibit diffuse reflectance and/or diffuse transmittance necessitating the use of an integrating sphere and a computer-controlled spectrometer to acquire accurate readings. This paper discusses the development of a standard test method to measure the quantum efficiency of QDs contained in solid organic and inorganic matrices. This standard is being developed under the auspices of the International Electrotechnical Commission, Technical Committee 113 on Nano-electrotechnologies.