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419 results on '"Mostafavi, S."'

5. Quantifying the Impact of Cannabis Smoking in Lungs of Young Adults Using CT and 129Xe MRI

Author

Eddy, R.L., primary, Mostafavi, S., additional, Schmidt, A., additional, Moo, K., additional, Lidher, L., additional, Li, A., additional, Gilchrist, C., additional, Leung, C., additional, Gerayeli, F.V., additional, Guinto, E., additional, Yang, J.S.W., additional, Cheung, C., additional, Guenette, J.A., additional, Rayment, J.H., additional, Gershon, A.S., additional, Sadatsafavi, M., additional, Tan, W.C., additional, Kirby, M., additional, Leipsic, J.A., additional, Sin, D.D., additional, and Leung, J.M., additional

Published
2024
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6. Plasmid-Mediated Colistin and Fosfomycin Resistance among Clinical Isolates of ESBL- and Carbapenemase-Producing Klebsiella Pneumoniae in Northern Iran.

Author

Falsafi, S., Ghasemian, A., Kohansal, M., Zarenezhad, E., Shokouhi Mostafavi, S. K., Rezaian, M., and Bakhtiari, A.

Subjects
MICROBIAL sensitivity tests, GENE amplification, DIAGNOSTIC use of polymerase chain reaction, POLYMERASE chain reaction, KLEBSIELLA pneumoniae, COLISTIN
Abstract

The emergence of extensively-resistant strains of Klebsiella pneumoniae (K. pneumoniae) in healthcare settings is linked to prolonged hospitalization and uncontrolled use of antibiotics. There is a paucity of data regarding the prevalence and mechanisms of colistin and fosfomycin resistance encoding genes rate and mechanisms in Iran. The objective of this study was to determine the prevalence of biofilm formation and fosfomycin and colistin resistance among K. pneumoniae strains producing ESBL and carbapenemases by detecting the mcr-1, mcr-2, and fosA genes in Tehran, Iran, during the 2020-2021 period. After collecting 73 samples, the isolates were identified using biochemical tests. Antibiotic susceptibility test was performed using the disk diffusion method. The phenotypic determination of extended-spectrum beta-lactamases (ESBLs) and carbapenemase enzymes was conducted using combined disk and CARBA-NP tests, respectively. The biofilm formation was conducted using a microtiter tissue plate assay. Polymerase chain reaction (PCR) was employed to detect the mcr-1, mcr-2 and fosA genes, which are associated with colistin and fosfomycin resistance, respectively. The highest resistance rate was observed against ampicillin (97%), chloramphenicol (90%), and ciprofloxacin (87%), respectively. In contrast, the lowest resistance rate was noted against gentamicin (4%), amikacin (10%), and cotrimoxazole (18%). Moreover, 44 and 23 isolates were identified as ESBL and carbapenemase -producing K. pneumonia), respectively. Of the fortyeight isolates that formed strong biofilms, one was a non-biofilm producer. The PCR test revealed the amplification of the fosA2 gene in four isolates and the mcr-2 genes in one isolate. However, no amplification of the fosA3 or mcr-1 genes was observed. The present study demonstrated that the frequency of K. pneumoniae isolates producing ESBL and carbapenemase, as well as mcr-1, mcr-2 and fosA genes, was relatively low. However, given the potential for these genes to be disseminated more widely, it is imperative to implement effective isolation and control measures. Moreover, these strains demonstrated the capacity to form biofilms in vitro, which can lead to persistent infections in the hospital settings. [ABSTRACT FROM AUTHOR]

Published
2024
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8. Vascular Calcification: An Important Understanding in Nephrology

Author

Zununi Vahed S, Mostafavi S, Hosseiniyan Khatibi SM, Shoja MM, and Ardalan M

Subjects
chronic kidney disease, ckd, uremic toxins, hyperphosphatemia, uremia, calcification, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Sepideh Zununi Vahed,1 Soroush Mostafavi,1 Seyed Mahdi Hosseiniyan Khatibi,1 Mohammadali M Shoja,2 Mohammadreza Ardalan1 1Kidney Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; 2Department of Surgery, University of Texas Medical Branch, Galveston, TX, USACorrespondence: Mohammadreza ArdalanKidney Research Center, Tabriz University of Medical Sciences, Tabriz, IranTel +98 914 116 8518Fax +98 41 3336 65 79Email ardalan34@yahoo.comAbstract: Vascular calcification (VC) is a life-threatening state in chronic kidney disease (CKD). High cardiovascular mortality and morbidity of CKD cases may root from medial VC promoted by hyperphosphatemia. Vascular calcification is an active, highly regulated, and complex biological process that is mediated by genetics, epigenetics, dysregulated form of matrix mineral metabolism, hormones, and the activation of cellular signaling pathways. Moreover, gut microbiome as a source of uremic toxins (eg, phosphate, advanced glycation end products and indoxyl-sulfate) can be regarded as a potential contributor to VC in CKD. Here, an update on different cellular and molecular processes involved in VC in CKD is discussed to elucidate the probable therapeutic pathways in the future.Keywords: chronic kidney disease, CKD, uremic toxins, hyperphosphatemia, uremia, calcification

Published
2020

9. Erratum: Consortium biology in immunology: The perspective from the Immunological Genome Project

Author

Benoist, C, Lanier, L, Merad, M, Mathis, D, Ericson, J, Painter, M, Davis, S, Laplace, C, Hyatt, G, Paik, H, Rothamel, K, Cruse, R, Doran, G, Heng, T, Asinovski, N, Ortiz-Lopes, A, Ergun, A, Gray, D, Wakamatsu, E, Hill, J, Mingueneau, M, Cipolletta, D, Yoshida, H, Cohen, N, Kim, E, Brennan, P, Lynch, L, Brenner, M, Costello, J, Collins, JJ, Blair, D, Dustin, M, Knell, J, Yang, E, Best, A, Shaw, L, Doedens, A, Goldrath, A, Shinton, S, Zhou, Y, Hardy, R, Jojic, V, Mostafavi, S, Koller, D, Jianu, R, Laidlaw, D, Bezman, N, Sun, J, Zhu, Y, Hendricks, D, Kamimura, Y, Min-Oo, G, Morvan, M, Nabekura, T, Lam, V, Kim, C, Greter, M, Helft, J, Chow, A, Bogunovic, M, Mortha, A, Price, J, Hashimoto, D, Miller, J, Sathe, P, Chudnovskiy, A, Lavin, Y, Idoyaga, J, Gautier, E, Jakubzick, C, D'Angelo, J, Randolph, G, Shay, T, Regev, A, Gazit, R, Rossi, D, Kreslawsky, T, von Bohmer, H, Bellemare-Pelletier, A, Elpek, K, Spelv, L, Fletcher, A, Malhotra, D, Cremasco, V, Turley, S, Kim, F, Nageswara Rao, T, and Wagers, A

Subjects
Immunology
Published
2014

10. Delay minimisation in network coding

Author

Mostafavi, S. Mostafa

Subjects
621.382
Abstract

Network coding is a promising generalization of routing which provides a mechanism to improve the performance of multicast networks. The core notion of network coding is to allow and encourage mixing of data at intermediate network nodes and enable the final receiver to deduce the original message from the mixed message data packets that it receives. Thanks to the above features; network coding seems an appealing solution in wireless networks that are characterized by limited energy, computational and communication resources. In the case of multicast network coding it is essential to have multipath routing from a source to destinations. The transmitted coded packets will be sent over different paths to the multiple receivers and then will be decoded at the receivers for data extraction once all the coded packets are received. A key component of an efficient network coding based on multipath routing in multicast networks is the delay minimisation that deals with how to minimise the delay of the encoded packets distributed amongst the multiple paths from a source to destinations. This is an important issue as coding is performed over a block of packets and the actual delay is the time needed for the receiver to wait for receiving all the necessary packets within the block for decoding. To address this issue, two broad set of approaches have been proposed in the literature. In the first category, delay reduction is achieved through better coding techniques whereas in the second approach, delay reduction is achieved through better routing and rate control schemes. In this thesis we have investigated delay minimisation in network coding based on multipath routing using an appropriate routing and rate control approach over the network. We have shown that delay minimisation in network coding from one source to several destinations is subset of delay minimisation on the multi path network from one source to one destination. To achieve such delay minimisation two strategies of average delay minimisation and maximum delay minimisation, through an appropriate route selection and traffic allocation were analytically investigated. Using analysis and simulation we have proved that delay synchronisation is the key policy for delay minimisation in network coding. Based on this finding we proposed an adaptive algorithm to achieve delay synchronisation. By applying this algorithm to the network coding scenario in butterfly network we have shown that the proposed end to end delay minimisation solution allows the network to obtain the maximum achievable throughput with finite delay.

Published
2010

16. Multi-angle data acquisition to compensate transducer finite size in photoacoustic tomography

Author

Hakakzadeh, Soheil (author), Mozaffarzadeh, M. (author), Mostafavi, S.. (author), Kavehvash, Zahra (author), Rajendran, Praveenbalaji (author), Verweij, M.D. (author), de Jong, N. (author), Pramanik, Manojit (author), Hakakzadeh, Soheil (author), Mozaffarzadeh, M. (author), Mostafavi, S.. (author), Kavehvash, Zahra (author), Rajendran, Praveenbalaji (author), Verweij, M.D. (author), de Jong, N. (author), and Pramanik, Manojit (author)

Abstract

In photoacoustic tomography (PAT) systems, the tangential resolution decreases due to the finite size of the transducer as the off-center distance increases. To address this problem, we propose a multi-angle detection approach in which the transducer used for data acquisition rotates around its center (with specific angles) as well as around the scanning center. The angles are calculated based on the central frequency and diameter of the transducer and the radius of the region-of-interest (ROI). Simulations with point-like absorbers (for point-spread-function evaluation) and a vasculature phantom (for quality assessment), and experiments with ten 0.5 mm-diameter pencil leads and a leaf skeleton phantom are used for evaluation of the proposed approach. The results show that a location-independent tangential resolution is achieved with 150 spatial sampling and central rotations with angles of ±8°/±16°. With further developments, the proposed detection strategy can replace the conventional detection (rotating a transducer around ROI) in PAT., ImPhys/Medical Imaging

Published
2022
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18. Building Resilient Communities Over Time

Author

Mehan, A., Mostafavi, S., Brears, R., and Brears, R.

Subjects
Societal Capacities, Urban Resilience, Digitalization, Community Resilience
Abstract

Community resilience entails the community’s ongoing and developing capacity to account for its vulnerabilities and function amid and recover from disturbance. A holistic and systematic approach of the community on how it uses material and energy resources or how a society educates the members’ over time is required to learn from the past and adapt to the present and future opportunities and threads. Community resilience has a long history in the local communities, which is embedded in their culture and history around shared values and local knowledge based on a dedicated and robust collaboration among diverse groups of the community and the various actors from different backgrounds. The innovative partnership between various actors such as stakeholders, research entities, local communities, and third sector parties is required to overcome the complexities of resiliency building. Using local knowledge to understand the local needs better is crucial in developing local, sustainable solutions and building community resilience over time.

Published
2022

23. Assessment of Bidirectional Relationships Between Physical Activity and Depression Among Adults A 2-Sample Mendelian Randomization Study

Author

Choi, K.W., Chen, C.Y., Stein, M.B., Klimentidis, Y.C., Wang, M.J., Koenen, K.C., Smoller, J.W., Wray, N.R., Ripke, S., Mattheisen, M., Trzaskowski, M., Byrne, E.M., Abdellaoui, A., Adams, M.J., Agerbo, E., Air, T., Andlauer, T.F.M., Bacanu, S.A., Baekvad-Hansen, M., Beekman, A.T.F., Bigdeli, T.B., Binder, E.B., Blackwood, D.H.R., Bryois, J., Buttenschon, H.N., Bybjerg-Grauholm, J., Cai, N., Castelao, E., Hvarregaard, J., Christensen, J.H., Clarke, T.K., Coleman, J.R.I., Colodro-Conde, L., Couvy-Duchesne, B., Craddock, N., Crawford, G.E., Davies, G., Deary, I.J., Degenhardt, F., Derks, E.M., Direk, N., Dolan, C.V., Dunn, E.C., Eley, T.C., Escott-Price, V., Kiadeh, F.F.H., Finucane, H.K., Forstner, A.J., Frank, J., Gaspar, H.A., Gill, M., Goes, F.S., Gordon, S.D., Grove, J., Hall, L.S., Hansen, C.S., Hansen, T.F., Herms, S., Hickie, I.B., Hoffmann, P., Homuth, G., Horn, C., Hottenga, J.J., Hougaard, D.M., Ising, M., Jansen, R., Jorgenson, E., Knowles, J.A., Kohane, I.S., Kraft, J., Kretzschmar, W., Krogh, J., Kutalik, Z., Li, Y.H., Lind, P.A., MacIntyre, D.J., MacKinnon, D.F., Maier, R.M., Marchini, J., McGrath, P., McGuffin, P., Medland, S.E., Mehta, D., Middeldorp, C.M., Mihailov, E., Milaneschi, Y., Milani, L., Mondimore, F.M., Montgomery, G.W., Mostafavi, S., Mullins, N., Nauck, M., Ng, B., Nivard, M.G., Nyholt, D.R., O'Reilly, P.F., Oskarsson, H., Owen, M.J., Painter, J.N., Pedersen, C.B., Pedersen, M.G., Peterson, R.E., Pettersson, E., Peyrot, W.J., Pistis, G., Posthuma, D., Quiroz, J.A., Qvist, P., Rice, J.P., Riley, B.P., Rivera, M., Saeed, S., Schoevers, R., Schulte, E.C., Shen, L., Shi, J.X., Shyn, S.I., Sigurdsson, E., Sinnamon, G.C.B., Smit, J.H., Smith, D.J., Stefansson, H., Steinberg, S., Streit, F., Strohmaier, J., Tansey, K.E., Teismann, H., Teumer, A., Thompson, W., Thomson, P.A., Thorgeirsson, T.E., Traylor, M., Treutlein, J., Trubetskoy, V., Uitterlinden, A.G., Umbricht, D., Auwera, S. van der, Hemert, A.M. van, Viktorin, A., Visscher, P.M., Wang, Y.P., Webb, B.T., Weinsheimer, S.M., Wellmann, J., Willemsen, G., Witt, S.H., Wu, Y., Xi, H.L.S., Yang, J., Zhang, F.T., Arolt, V., Baune, B.T., Berger, K., Boomsma, D.I., Cichon, S., Dannlowski, U., Geus, E.J.C. de, DePaulo, J.R., Domenici, E., Domschke, K., Esko, T., Grabe, H.J., Hamilton, S.P., Hayward, C., Heath, A.C., Kendler, K.S., Kloiber, S., Lewis, G., Li, Q.Q.S., Lucae, S., Madden, P.A.F., Magnusson, P.K., Martin, N.G., McIntosh, A.M., Metspalu, A., Mors, O., Mortensen, P.B., Nordentoft, M., Nothen, M.M., O'Donovan, M.C., Paciga, S.A., Pedersen, N.L., Penninx, B.W.J.H., Perlis, R.H., Porteous, D.J., Potash, J.B., Preisig, M., Rietschel, M., Schaefer, C., Schulze, T.G., Stefansson, K., Tiemeier, H., Uher, R., Volzke, H., Weissman, M.M., Werge, T., Lewis, C.M., Levinson, D.F., Breen, G., Borglum, A.D., Sullivan, P.F., Major Depressive Disorder Working, Epidemiology, Internal Medicine, Child and Adolescent Psychiatry / Psychology, Psychiatry, Biological Psychology, APH - Methodology, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, APH - Health Behaviors & Chronic Diseases, APH - Personalized Medicine, Complex Trait Genetics, Amsterdam Neuroscience - Complex Trait Genetics, APH - Mental Health, and Adult Psychiatry

Subjects
Adult, DISORDER, medicine.medical_specialty, Genome-wide association study, EXERCISE, CAUSALITY, 03 medical and health sciences, 0302 clinical medicine, SDG 3 - Good Health and Well-being, PEOPLE, Internal medicine, Accelerometry, Mendelian randomization, SCHIZOPHRENIA, Humans, Medicine, ANXIETY, Exercise, RISK, Depressive Disorder, Major, business.industry, Case-control study, SEDENTARY BEHAVIOR, Mendelian Randomization Analysis, Odds ratio, ASSOCIATION, Protective Factors, medicine.disease, 030227 psychiatry, Psychiatry and Mental health, Sample size determination, Case-Control Studies, Meta-analysis, Major depressive disorder, Self Report, business, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract

Importance: Increasing evidence shows that physical activity is associated with reduced risk for depression, pointing to a potential modifiable target for prevention. However, the causality and direction of this association are not clear; physical activity may protect against depression, and/or depression may result in decreased physical activity.Objective: To examine bidirectional relationships between physical activity and depression using a genetically informed method for assessing potential causal inference.Design, Setting, and Participants: This 2-sample mendelian randomization (MR) used independent top genetic variants associated with 2 physical activity phenotypes-self-reported (n = 377 234) and objective accelerometer-based (n = 91 084)-and with major depressive disorder (MDD) (n = 143 265) as genetic instruments from the largest available, nonoverlapping genome-wide association studies (GWAS). GWAS were previously conducted in diverse observational cohorts, including the UK Biobank (for physical activity) and participating studies in the Psychiatric Genomics Consortium (for MDD) among adults of European ancestry. Mendelian randomization estimates from each genetic instrument were combined using inverse variance weighted meta-analysis, with alternate methods (eg, weighted median, MR Egger, MR-Pleiotropy Residual Sum and Outlier [PRESSO]) and multiple sensitivity analyses to assess horizontal pleiotropy and remove outliers. Data were analyzed from May 10 through July 31, 2018.Main Outcomes and Measures: MDD and physical activity.Results: GWAS summary data were available for a combined sample size of 611 583 adult participants. Mendelian randomization evidence suggested a protective relationship between accelerometer-based activity and MDD (odds ratio [OR], 0.74 for MDD per 1-SD increase in mean acceleration; 95% CI, 0.59-0.92; P = .006). In contrast, there was no statistically significant relationship between MDD and accelerometer-based activity (β = -0.08 in mean acceleration per MDD vs control status; 95% CI, -0.47 to 0.32; P = .70). Furthermore, there was no significant relationship between self-reported activity and MDD (OR, 1.28 for MDD per 1-SD increase in metabolic-equivalent minutes of reported moderate-to-vigorous activity; 95% CI, 0.57-3.37; P = .48), or between MDD and self-reported activity (β = 0.02 per MDD in standardized metabolic-equivalent minutes of reported moderate-to-vigorous activity per MDD vs control status; 95% CI, -0.008 to 0.05; P = .15).Conclusions and Relevance: Using genetic instruments identified from large-scale GWAS, robust evidence supports a protective relationship between objectively assessed-but not self-reported-physical activity and the risk for MDD. Findings point to the importance of objective measurement of physical activity in epidemiologic studies of mental health and support the hypothesis that enhancing physical activity may be an effective prevention strategy for depression.

Published
2019

25. Region-specific, maladaptive, gray matter myelination is associated with differential susceptibility to stress-induced behavior in rats and humans

Author

Kazama Y, William Casazza, Toth Ce, Steven H. Woodward, Hu Ky, Jocelyn Breton, Misra R, Peretz L, Bertrand R. Huber, Thomas C. Neylan, Muller Dcy, Daniela Kaufer, Mostafavi S, Roan Vd, Long Klp, Chao Ll, and An A

Subjects
Myelin, medicine.anatomical_structure, Dentate gyrus, Stressor, Traumatic stress, medicine, Hippocampus, Biology, Neuroscience, Phenotype, Amygdala, Oligodendrocyte
Abstract

Background Individual reactions to traumatic stress vary dramatically, yet the biological basis of this variation remains poorly understood. Recent studies have demonstrated surprising plasticity of oligodendrocytes and myelin in the adult brain, providing a potential mechanism by which aberrant structural and functional changes arise in the brain following trauma exposure. Methods We tested the hypothesis that gray matter myelin contributes to traumatic stress-induced behavioral variation. We exposed adult rats to a single, severe stressor and used a multimodal approach to characterize avoidance, startle, and fear-learning behavior. We quantified oligodendrocyte and myelin content in multiple brain areas and compared these measures to behavioral metrics. We then induced overexpression of the oligodendrogenic transcription factor Olig1 in the adult rat dentate gyrus (DG) to test the potential, causal role of oligodendrogenesis in behavioral variation. Lastly, T1-/T2-weighted estimates of myelin were compared to trauma-induced symptom profiles in humans. Results Oligodendrocytes and myelin in the DG of the hippocampus positively correlated with stress-induced avoidance behaviors in male rats. In contrast, myelin levels in the amygdala positively correlated with contextual fear learning. Olig1 overexpression increased place avoidance compared to control virus animals, indicating that increased oligodendrocyte drive in the DG is sufficient to induce an avoidance behavioral phenotype. Finally, variation in myelin correlated with trauma-induced symptom profiles in humans in a region-specific manner that mirrored our rodent findings. Conclusions These results demonstrate a species-independent relationship between region-specific, gray matter oligodendrocytes and myelin and differential behavioral phenotypes following traumatic stress exposure. This study provides a novel biological framework for understanding the mechanisms that underlie individual variance in sensitivity to traumatic stress.

Published
2021

26. Worldwide trends in hypertension prevalence and progress in treatment and control from 1990 to 2019: a pooled analysis of 1201 population-representative studies with 104 million participants

Author

Zhou, B, Carrillo-Larco, RM, Danaei, G, Riley, LM, Paciorek, CJ, Stevens, GA, Gregg, EW, Bennett, JE, Solomon, B, Singleton, RK, Sophiea, MK, Iurilli, MLC, Lhoste, VPF, Cowan, MJ, Savin, S, Woodward, M, Balanova, Y, Cifkova, R, Damasceno, A, Elliott, P, Farzadfar, F, He, J, Ikeda, N, Kengne, AP, Khang, Y-H, Kim, HC, Laxmaiah, A, Lin, H-H, Margozzini Maira, P, Miranda, JJ, Neuhauser, H, Sundström, J, Varghese, C, Widyahening, IS, Zdrojewski, T, Abarca-Gómez, L, Abdeen, ZA, Abdul Rahim, HF, Abu-Rmeileh, NM, Acosta-Cazares, B, Adams, RJ, Aekplakorn, W, Afsana, K, Afzal, S, Agdeppa, IA, Aghazadeh-Attari, J, Aguilar-Salinas, CA, Agyemang, C, Ahmad, NA, Ahmadi, A, Ahmadi, N, Ahmadizar, F, Ahmed, SH, Ahrens, W, Ajlouni, K, Al-Raddadi, R, Alarouj, M, AlBuhairan, F, AlDhukair, S, Ali, MM, Alkandari, A, Alkerwi, A, Allin, K, Aly, E, Amarapurkar, DN, Amougou, N, Amouyel, P, Andersen, LB, Anderssen, SA, Anjana, RM, Ansari-Moghaddam, A, Ansong, D, Aounallah-Skhiri, H, Araújo, J, Ariansen, I, Aris, T, Arku, RE, Arlappa, N, Aryal, KK, Aspelund, T, Assah, FK, Assunção, MCF, Auvinen, J, Avdićová, M, Azevedo, A, Azimi-Nezhad, M, Azizi, F, Azmin, M, Babu, BV, Bahijri, S, Balakrishna, N, Bamoshmoosh, M, Banach, M, Banadinović, M, Bandosz, P, Banegas, JR, Baran, J, Barbagallo, CM, Barceló, A, Barkat, A, Barreto, M, Barros, AJD, Barros, MVG, Bartosiewicz, A, Basit, A, Bastos, JLD, Bata, I, Batieha, AM, Batyrbek, A, Baur, LA, Beaglehole, R, Belavendra, A, Ben Romdhane, H, Benet, M, Benson, LS, Berkinbayev, S, Bernabe-Ortiz, A, Bernotiene, G, Bettiol, H, Bezerra, J, Bhagyalaxmi, A, Bhargava, SK, Bia, D, Biasch, K, Bika Lele, EC, Bikbov, MM, Bista, B, Bjerregaard, P, Bjertness, E, Bjertness, MB, Björkelund, C, Bloch, KV, Blokstra, A, Bo, S, Bobak, M, Boeing, H, Boggia, JG, Boissonnet, CP, Bojesen, SE, Bongard, V, Bonilla-Vargas, A, Bopp, M, Borghs, H, Bovet, P, Boyer, CB, Braeckman, L, Brajkovich, I, Branca, F, Breckenkamp, J, Brenner, H, Brewster, LM, Briceño, Y, Brito, M, Bruno, G, Bueno-de-Mesquita, HB, Bueno, G, Bugge, A, Burns, C, Bursztyn, M, Cabrera de León, A, Cacciottolo, J, Cameron, C, Can, G, Cândido, APC, Capanzana, MV, Čapková, N, Capuano, E, Capuano, V, Cardoso, VC, Carlsson, AC, Carvalho, J, Casanueva, FF, Censi, L, Cervantes-Loaiza, M, Chadjigeorgiou, CA, Chamukuttan, S, Chan, AW, Chan, Q, Chaturvedi, HK, Chaturvedi, N, Chee, ML, Chen, C-J, Chen, F, Chen, H, Chen, S, Chen, Z, Cheng, C-Y, Cheraghian, B, Cherkaoui Dekkaki, I, Chetrit, A, Chien, K-L, Chiolero, A, Chiou, S-T, Chirita-Emandi, A, Chirlaque, M-D, Cho, B, Christensen, K, Christofaro, DG, Chudek, J, Cinteza, E, Claessens, F, Clarke, J, Clays, E, Cohen, E, Concin, H, Cooper, C, Coppinger, TC, Costanzo, S, Cottel, D, Cowell, C, Craig, CL, Crampin, AC, Crujeiras, AB, Cruz, JJ, Csilla, S, Cui, L, Cureau, FV, Cuschieri, S, D'Arrigo, G, d'Orsi, E, Dallongeville, J, Dankner, R, Dantoft, TM, Dauchet, L, Davletov, K, De Backer, G, De Bacquer, D, De Curtis, A, de Gaetano, G, De Henauw, S, de Oliveira, PD, De Ridder, D, De Smedt, D, Deepa, M, Deev, AD, DeGennaro, VJ, Delisle, H, Demarest, S, Dennison, E, Deschamps, V, Dhimal, M, Di Castelnuovo, AF, Dias-da-Costa, JS, Diaz, A, Dickerson, TT, Dika, Z, Djalalinia, S, Do, HTP, Dobson, AJ, Donfrancesco, C, Donoso, SP, Döring, A, Dorobantu, M, Dörr, M, Doua, K, Dragano, N, Drygas, W, Duante, CA, Duboz, P, Duda, RB, Dulskiene, V, Dushpanova, A, Džakula, A, Dzerve, V, Dziankowska-Zaborszczyk, E, Eddie, R, Eftekhar, E, Eggertsen, R, Eghtesad, S, Eiben, G, Ekelund, U, El-Khateeb, M, El Ati, J, Eldemire-Shearer, D, Eliasen, M, Elosua, R, Erasmus, RT, Erbel, R, Erem, C, Eriksen, L, Eriksson, JG, Escobedo-de la Peña, J, Eslami, S, Esmaeili, A, Evans, A, Faeh, D, Fakhretdinova, AA, Fall, CH, Faramarzi, E, Farjam, M, Fattahi, MR, Fawwad, A, Felix-Redondo, FJ, Felix, SB, Ferguson, TS, Fernandes, RA, Fernández-Bergés, D, Ferrante, D, Ferrao, T, Ferrari, M, Ferrario, MM, Ferreccio, C, Ferreira, HS, Ferrer, E, Ferrieres, J, Figueiró, TH, Fink, G, 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Jureša, V, Kaaks, R, Kafatos, A, Kajantie, EO, Kalmatayeva, Z, Kalpourtzi, N, Kalter-Leibovici, O, Kampmann, FB, Kannan, S, Karaglani, E, Kårhus, LL, Karki, KB, Katibeh, M, Katz, J, Kauhanen, J, Kaur, P, Kavousi, M, Kazakbaeva, GM, Keil, U, Keinan Boker, L, Keinänen-Kiukaanniemi, S, Kelishadi, R, Kemper, HCG, Keramati, M, Kerimkulova, A, Kersting, M, Key, T, Khader, YS, Khalili, D, Khaw, K-T, Kheiri, B, Kheradmand, M, Khosravi, A, Kiechl-Kohlendorfer, U, Kiechl, S, Killewo, J, Kim, DW, Kim, J, Klakk, H, Klimek, M, Klumbiene, J, Knoflach, M, Kolle, E, Kolsteren, P, Kontto, JP, Korpelainen, R, Korrovits, P, Kos, J, Koskinen, S, Kouda, K, Kowlessur, S, Koziel, S, Kratenova, J, Kriaucioniene, V, Kristensen, PL, Krokstad, S, Kromhout, D, Kruger, HS, Kubinova, R, Kuciene, R, Kujala, UM, Kulaga, Z, Kumar, RK, Kurjata, P, Kusuma, YS, Kutsenko, V, Kuulasmaa, K, Kyobutungi, C, Laatikainen, T, Lachat, C, Laid, Y, Lam, TH, Landrove, O, Lanska, V, Lappas, G, Larijani, B, Latt, TS, Le Coroller, G, Le Nguyen Bao, K, Le, TD, Lee, J, Lehmann, N, Lehtimäki, T, Lemogoum, D, Levitt, NS, Li, Y, Lilly, CL, Lim, W-Y, Lima-Costa, MF, Lin, X, Lin, Y-T, Lind, L, Lingam, V, Linneberg, A, Lissner, L, Litwin, M, Lo, W-C, Loit, H-M, Lopez-Garcia, E, Lopez, T, Lotufo, PA, Lozano, JE, Lukačević Lovrenčić, I, Lukrafka, JL, Luksiene, D, Lundqvist, A, Lundqvist, R, Lunet, N, Lustigová, M, Luszczki, E, Ma, G, Ma, J, Machado-Coelho, GLL, Machado-Rodrigues, AM, Macia, E, Macieira, LM, Madar, AA, Maggi, S, Magliano, DJ, Magriplis, E, Mahasampath, G, Maire, B, Majer, M, Makdisse, M, Malekzadeh, F, Malekzadeh, R, Malhotra, R, Mallikharjuna Rao, K, Malyutina, SK, Maniego, LV, Manios, Y, Mann, JI, Mansour-Ghanaei, F, Manzato, E, Marcil, A, Mårild, SB, Marinović Glavić, M, Marques-Vidal, P, Marques, LP, Marrugat, J, Martorell, R, Mascarenhas, LP, Matasin, M, Mathiesen, EB, Mathur, P, Matijasevich, A, Matlosz, P, Matsha, TE, Mavrogianni, C, Mbanya, JCN, Mc Donald Posso, AJ, McFarlane, SR, McGarvey, ST, McLachlan, S, McLean, RM, McLean, SB, McNulty, BA, Mediene Benchekor, S, Medzioniene, J, Mehdipour, P, Mehlig, K, Mehrparvar, AH, Meirhaeghe, A, Meisinger, C, Mendoza Montano, C, Menezes, AMB, Menon, GR, Mereke, A, Meshram, II, Metspalu, A, Meyer, HE, Mi, J, Michels, N, Mikkel, K, Milkowska, K, Miller, JC, Minderico, CS, Mini, GK, Mirjalili, MR, Mirrakhimov, E, Mišigoj-Duraković, M, Modesti, PA, Moghaddam, SS, Mohajer, B, Mohamed, MK, Mohamed, SF, Mohammad, K, Mohammadi, MR, Mohammadi, Z, Mohammadifard, N, Mohammadpourhodki, R, Mohan, V, Mohanna, S, Mohd Yusoff, MF, Mohebbi, I, Mohebi, F, Moitry, M, Møllehave, LT, Molnár, D, Momenan, A, Mondo, CK, Monterrubio-Flores, E, Monyeki, KDK, Moon, JS, Moosazadeh, M, Moreira, LB, Morejon, A, Moreno, LA, Morgan, K, Moschonis, G, Mossakowska, M, Mostafa, A, Mostafavi, S-A, Mota, J, Motlagh, ME, Motta, J, Moura-dos-Santos, MA, Mridha, MK, Msyamboza, KP, Mu, TT, Muhihi, AJ, Muiesan, ML, Müller-Nurasyid, M, Murphy, N, Mursu, J, Musa, KI, Musić Milanović, S, Musil, V, Mustafa, N, Nabipour, I, Naderimagham, S, Nagel, G, Naidu, BM, Najafi, F, Nakamura, H, Námešná, J, Nang, EEK, Nangia, VB, Narake, S, Ndiaye, NC, Neal, WA, Nejatizadeh, A, Nenko, I, Neovius, M, Nguyen, CT, Nguyen, ND, Nguyen, QV, Nguyen, QN, Nieto-Martínez, RE, Niiranen, TJ, Nikitin, YP, Ninomiya, T, Nishtar, S, Njelekela, MA, Noale, M, Noboa, OA, Noorbala, AA, Norat, T, Nordendahl, M, Nordestgaard, BG, Noto, D, Nowak-Szczepanska, N, Nsour, MA, Nunes, B, O'Neill, TW, O'Reilly, D, Ochimana, C, Oda, E, Odili, AN, Oh, K, Ohara, K, Ohtsuka, R, Olié, V, Olinto, MTA, Oliveira, IO, Omar, MA, Onat, A, Ong, SK, Ono, LM, Ordunez, P, Ornelas, R, Ortiz, PJ, Osmond, C, Ostojic, SM, Ostovar, A, Otero, JA, Overvad, K, Owusu-Dabo, E, Paccaud, FM, Padez, C, Pahomova, E, Paiva, KMD, Pająk, A, Palli, D, Palmieri, L, Pan, W-H, Panda-Jonas, S, Panza, F, Paoli, M, Papandreou, D, Park, S-W, Park, S, Parnell, WR, Parsaeian, M, Pasquet, P, Patel, ND, Pavlyshyn, H, Pećin, I, Pednekar, MS, Pedro, JM, Peer, N, Peixoto, SV, Peltonen, M, Pereira, AC, Peres, KGDA, Peres, MA, Peters, A, Petkeviciene, J, Peykari, N, Pham, ST, Pichardo, RN, Pigeot, I, Pikhart, H, Pilav, A, Pilotto, L, Pitakaka, F, Piwonska, A, Pizarro, AN, Plans-Rubió, P, Polašek, O, Porta, M, Poudyal, A, Pourfarzi, F, Pourshams, A, Poustchi, H, Pradeepa, R, Price, AJ, Price, JF, Providencia, R, Puhakka, SE, Puiu, M, Punab, M, Qasrawi, RF, Qorbani, M, Queiroz, D, Quoc Bao, T, Radić, I, Radisauskas, R, Rahimikazerooni, S, Rahman, M, Raitakari, O, Raj, M, Rakhimova, EM, and Ra

Published
2021

28. Decoding differential gene expression

Author

Yanling Wang, Mostafavi S, Shinya Tasaki, and Chris Gaiteri

Subjects
Regulation of gene expression, 0303 health sciences, business.industry, Computer science, Systems biology, Deep learning, 030302 biochemistry & molecular biology, Big data, Variation (game tree), Computational biology, 03 medical and health sciences, Gene expression, Artificial intelligence, Differential (infinitesimal), business, Decoding methods, 030304 developmental biology
Abstract

Identifying the molecular mechanisms that control differential gene expression (DE) is a major goal of basic and disease biology. Combining the strengths of systems biology and deep learning in a model called DEcode, we are able to predict DE more accurately than traditional sequence-based methods, which do not utilize systems biology data. To determine the biological origins of this accuracy, we identify the most predictive regulators and types of regulatory interactions in DEcode, contrasting their roles across many human tissues. Diverse systems biology, ontological and disease-related assessments all point to the predominant influence of post-translational RNA-binding factors on DE. Through the combinatorial gene regulation that is captured in DEcode, it is even possible to predict relatively subtle person-to-person variation in gene expression. We demonstrate the broad applicability of these clinically-relevant predictions by predicting drivers of aging throughout the human lifespan, gene coexpression relationships on a genome-wide scale, and frequent DE in diverse conditions. Researchers can freely access DEcode to utilize genomic big data in identifying influential molecular mechanisms for any human expression data - www.differentialexpression.org.

Published
2020
Full Text
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29. metPropagate: network-guided propagation of metabolomic information for prioritization of metabolic disease genes

Author

Graham Linck, Emma J., Richmond, Phillip A., Tarailo-Graovac, M., Engelke, U.F.H., Kluijtmans, L.A.J., Coene, K.L.M., Wevers, R.A., Karnebeek, C.D. van, Mostafavi, S., Graham Linck, Emma J., Richmond, Phillip A., Tarailo-Graovac, M., Engelke, U.F.H., Kluijtmans, L.A.J., Coene, K.L.M., Wevers, R.A., Karnebeek, C.D. van, and Mostafavi, S.

Abstract

Contains fulltext : 220744.pdf (publisher's version ) (Open Access)

Published
2020

30. Classical Human Leukocyte Antigen Alleles and C4 Haplotypes Are Not Significantly Associated With Depression

Author

Glanville, KP, Coleman, JR, Hanscombe, KB, Euesden, J, Choi, SW, Purves, KL, Breen, G, Air, TM, Andlauer, TFM, Baune, BT, Binder, EB, Blackwood, DHR, Boomsma, D, Buttenschon, HN, Colodro-Conde, L, Dannlowski, U, Direk, N, Dunn, EC, Forstner, AJ, de Geus, EJC, Grabe, HJ, Hamilton, SP, Jones, I, Jones, LA, Knowles, JA, Kutalik, Z, Levinson, DF, Lewis, G, Lind, PA, Lucae, S, Magnusson, PK, McGuffin, P, McIntosh, AM, Milaneschi, Y, Mors, O, Mostafavi, S, Mueller-Myhsok, B, Pedersen, NL, Penninx, BWJH, Potash, JB, Preisig, M, Ripke, S, Shi, J, Shyn, S, Smoller, JW, Streit, F, Sullivan, PF, Tiemeier, H, Uher, R, Van der Auwera, S, Weissman, MM, O'Reilly, PF, Lewis, CM, Wray, NR, Mattheisen, M, Trzaskowski, M, Byrne, EM, Abdellaoui, A, Adams, MJ, Agerbo, E, Bacanu, S-A, Baekvad-Hansen, M, Beekman, ATF, Bigdeli, TB, Bryois, J, Bybjerg-Grauholm, J, Cai, N, Castelao, E, Christensen, JH, Clarke, T-K, Couvy-Duchesne, B, Craddock, N, Crawford, GE, Davies, G, Deary, IJ, Degenhardt, F, Derks, EM, Dolan, C, Eley, TC, Escott-Price, V, Kiadeh, FFH, Finucane, HK, Foo, JC, Frank, J, Gaspar, HA, Gill, M, Goes, FS, Gordon, SD, Grove, J, Hall, LS, Hansen, CS, Hansen, TF, Herms, S, Hickie, IB, Hoffmann, P, Homuth, G, Horn, C, Hottenga, J-J, Hougaard, DM, Howard, DM, Ising, M, Jansen, R, Jorgenson, E, Kohane, IS, Kraft, J, Kretzschmar, WW, Li, Y, MacIntyre, DJ, MacKinnon, DF, Maier, RM, Maier, W, Marchini, J, Mbarek, H, McGrath, P, Medland, SE, Mehta, D, Middeldorp, CM, Mihailov, E, Milani, L, Mondimore, FM, Montgomery, GW, Mullins, N, Nauck, M, Ng, B, Nivard, MG, Nyholt, DR, Oskarsson, H, Owen, MJ, Painter, JN, Pedersen, CB, Pedersen, MG, Peterson, RE, Pettersson, E, Peyrot, WJ, Pistis, G, Posthuma, D, Quiroz, JA, Qvist, P, Rice, JP, Riley, BP, Rivera, M, Mirza, SS, Schoevers, R, Schulte, EC, Shen, L, Sigurdsson, E, Sinnamon, GCB, Smit, JH, Smith, DJ, Stefansson, H, Steinberg, S, Strohmaier, J, Tansey, KE, Teismann, H, Teumer, A, Thompson, W, Thomson, PA, Thorgeirsson, TE, Traylor, M, Treutlein, J, Trubetskoy, V, Uitterlinden, AG, Umbricht, D, van Hemert, AM, Viktorin, A, Visscher, PM, Wang, Y, Webb, BT, Weinsheimer, SM, Wellmann, J, Willemsen, G, Witt, SH, Wu, Y, Xi, HS, Yang, J, Zhang, F, Arolt, V, Berger, K, Cichon, S, DePaulo, JR, Domenici, E, Domschke, K, Esko, T, Hayward, C, Heath, AC, Kendler, KS, Kloiber, S, Li, QS, Madden, PAF, Martin, NG, Metspalu, A, Mortensen, PB, Nordentoft, M, Noethen, MM, O'Donovan, MC, Paciga, SA, Perlis, RH, Porteous, DJ, Rietschel, M, Schaefer, C, Schulze, TG, Stefansson, K, Voelzke, H, Werge, T, Borglum, AD, Glanville, KP, Coleman, JR, Hanscombe, KB, Euesden, J, Choi, SW, Purves, KL, Breen, G, Air, TM, Andlauer, TFM, Baune, BT, Binder, EB, Blackwood, DHR, Boomsma, D, Buttenschon, HN, Colodro-Conde, L, Dannlowski, U, Direk, N, Dunn, EC, Forstner, AJ, de Geus, EJC, Grabe, HJ, Hamilton, SP, Jones, I, Jones, LA, Knowles, JA, Kutalik, Z, Levinson, DF, Lewis, G, Lind, PA, Lucae, S, Magnusson, PK, McGuffin, P, McIntosh, AM, Milaneschi, Y, Mors, O, Mostafavi, S, Mueller-Myhsok, B, Pedersen, NL, Penninx, BWJH, Potash, JB, Preisig, M, Ripke, S, Shi, J, Shyn, S, Smoller, JW, Streit, F, Sullivan, PF, Tiemeier, H, Uher, R, Van der Auwera, S, Weissman, MM, O'Reilly, PF, Lewis, CM, Wray, NR, Mattheisen, M, Trzaskowski, M, Byrne, EM, Abdellaoui, A, Adams, MJ, Agerbo, E, Bacanu, S-A, Baekvad-Hansen, M, Beekman, ATF, Bigdeli, TB, Bryois, J, Bybjerg-Grauholm, J, Cai, N, Castelao, E, Christensen, JH, Clarke, T-K, Couvy-Duchesne, B, Craddock, N, Crawford, GE, Davies, G, Deary, IJ, Degenhardt, F, Derks, EM, Dolan, C, Eley, TC, Escott-Price, V, Kiadeh, FFH, Finucane, HK, Foo, JC, Frank, J, Gaspar, HA, Gill, M, Goes, FS, Gordon, SD, Grove, J, Hall, LS, Hansen, CS, Hansen, TF, Herms, S, Hickie, IB, Hoffmann, P, Homuth, G, Horn, C, Hottenga, J-J, Hougaard, DM, Howard, DM, Ising, M, Jansen, R, Jorgenson, E, Kohane, IS, Kraft, J, Kretzschmar, WW, Li, Y, MacIntyre, DJ, MacKinnon, DF, Maier, RM, Maier, W, Marchini, J, Mbarek, H, McGrath, P, Medland, SE, Mehta, D, Middeldorp, CM, Mihailov, E, Milani, L, Mondimore, FM, Montgomery, GW, Mullins, N, Nauck, M, Ng, B, Nivard, MG, Nyholt, DR, Oskarsson, H, Owen, MJ, Painter, JN, Pedersen, CB, Pedersen, MG, Peterson, RE, Pettersson, E, Peyrot, WJ, Pistis, G, Posthuma, D, Quiroz, JA, Qvist, P, Rice, JP, Riley, BP, Rivera, M, Mirza, SS, Schoevers, R, Schulte, EC, Shen, L, Sigurdsson, E, Sinnamon, GCB, Smit, JH, Smith, DJ, Stefansson, H, Steinberg, S, Strohmaier, J, Tansey, KE, Teismann, H, Teumer, A, Thompson, W, Thomson, PA, Thorgeirsson, TE, Traylor, M, Treutlein, J, Trubetskoy, V, Uitterlinden, AG, Umbricht, D, van Hemert, AM, Viktorin, A, Visscher, PM, Wang, Y, Webb, BT, Weinsheimer, SM, Wellmann, J, Willemsen, G, Witt, SH, Wu, Y, Xi, HS, Yang, J, Zhang, F, Arolt, V, Berger, K, Cichon, S, DePaulo, JR, Domenici, E, Domschke, K, Esko, T, Hayward, C, Heath, AC, Kendler, KS, Kloiber, S, Li, QS, Madden, PAF, Martin, NG, Metspalu, A, Mortensen, PB, Nordentoft, M, Noethen, MM, O'Donovan, MC, Paciga, SA, Perlis, RH, Porteous, DJ, Rietschel, M, Schaefer, C, Schulze, TG, Stefansson, K, Voelzke, H, Werge, T, and Borglum, AD

Abstract

BACKGROUND: The prevalence of depression is higher in individuals with autoimmune diseases, but the mechanisms underlying the observed comorbidities are unknown. Shared genetic etiology is a plausible explanation for the overlap, and in this study we tested whether genetic variation in the major histocompatibility complex (MHC), which is associated with risk for autoimmune diseases, is also associated with risk for depression. METHODS: We fine-mapped the classical MHC (chr6: 29.6-33.1 Mb), imputing 216 human leukocyte antigen (HLA) alleles and 4 complement component 4 (C4) haplotypes in studies from the Psychiatric Genomics Consortium Major Depressive Disorder Working Group and the UK Biobank. The total sample size was 45,149 depression cases and 86,698 controls. We tested for association between depression status and imputed MHC variants, applying both a region-wide significance threshold (3.9 × 10-6) and a candidate threshold (1.6 × 10-4). RESULTS: No HLA alleles or C4 haplotypes were associated with depression at the region-wide threshold. HLA-B*08:01 was associated with modest protection for depression at the candidate threshold for testing in HLA genes in the meta-analysis (odds ratio = 0.98, 95% confidence interval = 0.97-0.99). CONCLUSIONS: We found no evidence that an increased risk for depression was conferred by HLA alleles, which play a major role in the genetic susceptibility to autoimmune diseases, or C4 haplotypes, which are strongly associated with schizophrenia. These results suggest that any HLA or C4 variants associated with depression either are rare or have very modest effect sizes.

Published
2020

31. Genome-wide gene-environment analyses of major depressive disorder and reported lifetime traumatic experiences in UK Biobank

Author

Coleman, JRI, Peyrot, WJ, Purves, KL, Davis, KAS, Rayner, C, Choi, SW, Hubel, C, Gaspar, HA, Kan, C, Van der Auwera, S, Adams, MJ, Lyall, DM, Choi, KW, Dunn, EC, Vassos, E, Danese, A, Maughan, B, Grabe, HJ, Lewis, CM, O'Reilly, PF, McIntosh, AM, Smith, DJ, Wray, NR, Hotopf, M, Eley, TC, Breen, G, Ripke, S, Mattheisen, M, Trzaskowski, M, Byrne, EM, Abdellaoui, A, Agerbo, E, Air, TM, Andlauer, TFM, Bacanu, S-A, Baekvad-Hansen, M, Beekman, ATF, Bigdeli, TB, Binder, EB, Bryois, J, Buttenschon, HN, Bybjerg-Grauholm, J, Cai, N, Castelao, E, Christensen, JH, Clarke, T-K, Colodro-Conde, L, Couvy-Duchesne, B, Craddock, N, Crawford, GE, Davies, G, Deary, IJ, Degenhardt, F, Derks, EM, Direk, N, Dolan, CV, Escott-Price, V, Kiadeh, FFH, Finucane, HK, Foo, JC, Forstner, AJ, Frank, J, Gill, M, Goes, FS, Gordon, SD, Grove, J, Hall, LS, Hansen, CS, Hansen, TF, Herms, S, Hickie, IB, Hoffmann, P, Homuth, G, Horn, C, Hottenga, J-J, Hougaard, DM, Howard, DM, Ising, M, Jansen, R, Jones, I, Jones, LA, Jorgenson, E, Knowles, JA, Kohane, IS, Kraft, J, Kretzschmar, WW, Kutalik, Z, Li, Y, Lind, PA, MacIntyre, DJ, MacKinnon, DF, Maier, RM, Maier, W, Marchini, J, Mbarek, H, McGrath, P, McGuffin, P, Medland, SE, Mehta, D, Middeldorp, CM, Mihailov, E, Milaneschi, Y, Milani, L, Mondimore, FM, Montgomery, GW, Mostafavi, S, Mullins, N, Nauck, M, Ng, B, Nivard, MG, Nyholt, DR, Oskarsson, H, Owen, MJ, Painter, JN, Pedersen, CB, Pedersen, MG, Peterson, RE, Pettersson, E, Pistis, G, Posthuma, D, Quiroz, JA, Qvist, P, Rice, JP, Riley, BP, Rivera, M, Mirza, SS, Schoevers, R, Schulte, EC, Shen, L, Shi, J, Shyn, SI, Sigurdsson, E, Sinnamon, GCB, Smit, JH, Stefansson, H, Steinberg, S, Streit, F, Strohmaier, J, Tansey, KE, Teismann, H, Teumer, A, Thompson, W, Thomson, PA, Thorgeirsson, TE, Traylor, M, Treutlein, J, Trubetskoy, V, Uitterlinden, AG, Umbricht, D, van Hemert, AM, Viktorin, A, Visscher, PM, Wang, Y, Webb, BT, Weinsheimer, SM, Wellmann, J, Willemsen, G, Witt, SH, Wu, Y, Xi, HS, Yang, J, Zhang, F, Arolt, V, Baune, BT, Berger, K, Boomsma, DI, Cichon, S, Dannlowski, U, de Geus, EJC, DePaulo, JR, Domenici, E, Domschke, K, Esko, T, Hamilton, SP, Hayward, C, Heath, AC, Kendler, KS, Kloiber, S, Lewis, G, Li, QS, Lucae, S, Madden, PAF, Magnusson, PK, Martin, NG, Metspalu, A, Mors, O, Mortensen, PB, Mueller-Myhsok, B, Nordentoft, M, Noethen, MM, O'Donovan, MC, Paciga, SA, Pedersen, NL, Penninx, BWJH, Perlis, RH, Porteous, DJ, Potash, JB, Preisig, M, Rietschel, M, Schaefer, C, Schulze, TG, Smoller, JW, Stefansson, K, Tiemeier, H, Uher, R, Volzke, H, Weissman, MM, Werge, T, Levinson, DF, Borglum, AD, Sullivan, PF, Coleman, JRI, Peyrot, WJ, Purves, KL, Davis, KAS, Rayner, C, Choi, SW, Hubel, C, Gaspar, HA, Kan, C, Van der Auwera, S, Adams, MJ, Lyall, DM, Choi, KW, Dunn, EC, Vassos, E, Danese, A, Maughan, B, Grabe, HJ, Lewis, CM, O'Reilly, PF, McIntosh, AM, Smith, DJ, Wray, NR, Hotopf, M, Eley, TC, Breen, G, Ripke, S, Mattheisen, M, Trzaskowski, M, Byrne, EM, Abdellaoui, A, Agerbo, E, Air, TM, Andlauer, TFM, Bacanu, S-A, Baekvad-Hansen, M, Beekman, ATF, Bigdeli, TB, Binder, EB, Bryois, J, Buttenschon, HN, Bybjerg-Grauholm, J, Cai, N, Castelao, E, Christensen, JH, Clarke, T-K, Colodro-Conde, L, Couvy-Duchesne, B, Craddock, N, Crawford, GE, Davies, G, Deary, IJ, Degenhardt, F, Derks, EM, Direk, N, Dolan, CV, Escott-Price, V, Kiadeh, FFH, Finucane, HK, Foo, JC, Forstner, AJ, Frank, J, Gill, M, Goes, FS, Gordon, SD, Grove, J, Hall, LS, Hansen, CS, Hansen, TF, Herms, S, Hickie, IB, Hoffmann, P, Homuth, G, Horn, C, Hottenga, J-J, Hougaard, DM, Howard, DM, Ising, M, Jansen, R, Jones, I, Jones, LA, Jorgenson, E, Knowles, JA, Kohane, IS, Kraft, J, Kretzschmar, WW, Kutalik, Z, Li, Y, Lind, PA, MacIntyre, DJ, MacKinnon, DF, Maier, RM, Maier, W, Marchini, J, Mbarek, H, McGrath, P, McGuffin, P, Medland, SE, Mehta, D, Middeldorp, CM, Mihailov, E, Milaneschi, Y, Milani, L, Mondimore, FM, Montgomery, GW, Mostafavi, S, Mullins, N, Nauck, M, Ng, B, Nivard, MG, Nyholt, DR, Oskarsson, H, Owen, MJ, Painter, JN, Pedersen, CB, Pedersen, MG, Peterson, RE, Pettersson, E, Pistis, G, Posthuma, D, Quiroz, JA, Qvist, P, Rice, JP, Riley, BP, Rivera, M, Mirza, SS, Schoevers, R, Schulte, EC, Shen, L, Shi, J, Shyn, SI, Sigurdsson, E, Sinnamon, GCB, Smit, JH, Stefansson, H, Steinberg, S, Streit, F, Strohmaier, J, Tansey, KE, Teismann, H, Teumer, A, Thompson, W, Thomson, PA, Thorgeirsson, TE, Traylor, M, Treutlein, J, Trubetskoy, V, Uitterlinden, AG, Umbricht, D, van Hemert, AM, Viktorin, A, Visscher, PM, Wang, Y, Webb, BT, Weinsheimer, SM, Wellmann, J, Willemsen, G, Witt, SH, Wu, Y, Xi, HS, Yang, J, Zhang, F, Arolt, V, Baune, BT, Berger, K, Boomsma, DI, Cichon, S, Dannlowski, U, de Geus, EJC, DePaulo, JR, Domenici, E, Domschke, K, Esko, T, Hamilton, SP, Hayward, C, Heath, AC, Kendler, KS, Kloiber, S, Lewis, G, Li, QS, Lucae, S, Madden, PAF, Magnusson, PK, Martin, NG, Metspalu, A, Mors, O, Mortensen, PB, Mueller-Myhsok, B, Nordentoft, M, Noethen, MM, O'Donovan, MC, Paciga, SA, Pedersen, NL, Penninx, BWJH, Perlis, RH, Porteous, DJ, Potash, JB, Preisig, M, Rietschel, M, Schaefer, C, Schulze, TG, Smoller, JW, Stefansson, K, Tiemeier, H, Uher, R, Volzke, H, Weissman, MM, Werge, T, Levinson, DF, Borglum, AD, and Sullivan, PF

Abstract

Depression is more frequent among individuals exposed to traumatic events. Both trauma exposure and depression are heritable. However, the relationship between these traits, including the role of genetic risk factors, is complex and poorly understood. When modelling trauma exposure as an environmental influence on depression, both gene-environment correlations and gene-environment interactions have been observed. The UK Biobank concurrently assessed Major Depressive Disorder (MDD) and self-reported lifetime exposure to traumatic events in 126,522 genotyped individuals of European ancestry. We contrasted genetic influences on MDD stratified by reported trauma exposure (final sample size range: 24,094-92,957). The SNP-based heritability of MDD with reported trauma exposure (24%) was greater than MDD without reported trauma exposure (12%). Simulations showed that this is not confounded by the strong, positive genetic correlation observed between MDD and reported trauma exposure. We also observed that the genetic correlation between MDD and waist circumference was only significant in individuals reporting trauma exposure (rg = 0.24, p = 1.8 × 10-7 versus rg = -0.05, p = 0.39 in individuals not reporting trauma exposure, difference p = 2.3 × 10-4). Our results suggest that the genetic contribution to MDD is greater when reported trauma is present, and that a complex relationship exists between reported trauma exposure, body composition, and MDD.

Published
2020

39. DOP64 Discovery of highly selective small-molecule oral inhibitors of integrin α4β7 for the treatment of inflammatory bowel diseases

Author

WONG, J, primary, Bursavich, M, additional, Blanco, N, additional, Camblin, A, additional, Cappellucci, L, additional, Cohen, R, additional, Cui, D, additional, Krumpoch, M, additional, Zhong, C, additional, Hahn, K, additional, Lee, D, additional, Lippa, B, additional, Lin, F Y, additional, Lugovsky, A, additional, McShea, M, additional, Mostafavi, S, additional, Moy, T, additional, Sullivan, A, additional, Troast, D, additional, Wang, L, additional, and Rogers, B, additional

Published
2020
Full Text
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40. Identification of common genetic risk variants for autism spectrum disorder

Author

Grove, J., Ripke, S., Als, T.D., Mattheisen, M., Walters, R.K., Won, H., Pallesen, J., Agerbo, E., Andreassen, O.A., Anney, R., Awashti, S., Belliveau, R., Bettella, F., Buxbaum, J.D., Bybjerg-Grauholm, J., Baekvad-Hansen, M., Cerrato, F., Chambert, K., Christensen, J.H., Churchhouse, C., Dellenvall, K., Demontis, D., Rubeis, S. de, Devlin, B., Djurovic, S., Dumont, A.L., Goldstein, J.I., Hansen, C.S., Hauberg, M.E., Hollegaard, M.V., Hope, S., Howrigan, D.P., Huang, H., Hultman, C.M., Klei, L., Maller, J., Martin, J., Martin, A.R., Moran, J.L., Nyegaard, M., Naeland, T., Palmer, D.S., Palotie, A., Pedersen, C.B., Pedersen, M.G., dPoterba, T., Poulsen, J.B., St Pourcain, B., Qvist, P., Rehnstrom, K., Reichenberg, A., Reichert, J., Robinson, E.B., Roeder, K., Roussos, P., Saemundsen, E., Sandin, S., Satterstrom, F.K., Smith, G.D., Stefansson, H., Steinberg, S., Stevens, C.R., Sullivan, P.F., Turley, P., Walters, G.B., Xu, X.Y., Stefansson, K., Geschwind, D.H., Nordentoft, M., Hougaard, D.M., Werge, T., Mors, O., Mortensen, P.B., Neale, B.M., Daly, M.J., Borglum, A.D., Wray, N.R., Trzaskowski, M., Byrne, E.M., Abdellaoui, A., Adams, M.J., Air, T.M., Andlauer, T.F.M., Bacanu, S.A., Beekman, A.T.F., Bigdeli, T.B., Binder, E.B., Blackwood, D.H.R., Bryois, J., Buttenschon, H.N., Cai, N., Castelao, E., Clarke, T.K., Coleman, J.R.I., Colodro-Conde, L., Couvy-Duchesne, B., Craddock, N., Crawford, G.E., Davies, G., Deary, I.J., Degenhardt, F., Derks, E.M., Direk, N., Dolan, C.V., Dunn, E.C., Eley, T.C., Escott-Price, V., Kiadeh, F.F.H., Finucane, H.K., Forstner, A.J., Frank, J., Gaspar, H.A., Gill, M., Goes, F.S., Gordon, S.D., Hall, L.S., Hansen, T.F., Herms, S., Hickie, I.B., Hoffmann, P., Homuth, G., Horn, C., Hottenga, J.J., Ising, M., Jansen, R., Jorgenson, E., Knowles, J.A., Kohane, I.S., Kraft, J., Kretzschmar, W.W., Krogh, J., Kutalik, Z., Li, Y., Lind, P.A., MacIntyre, D.J., MacKinnon, D.F., Maier, R.M., Maier, W., Marchini, J., Mbarek, H., McGrath, P., McGuffin, P., Medland, S.E., Mehta, D., Middeldorp, C.M., Mihailov, E., Milaneschi, Y., Milani, L., Mondimore, F.M., Montgomery, G.W., Mostafavi, S., Mullins, N., Nauck, M., Ng, B., Nivard, M.G., Nyholt, D.R., O'Reilly, P.F., Oskarsson, H., Owen, M.J., Painter, J.N., Peterson, R.E., Pettersson, E., Peyrot, W.J., Pistis, G., Posthuma, D., Quiroz, J.A., Rice, J.P., Riley, B.P., Rivera, M., Mirza, S.S., Schoevers, R., Schulte, E.C., Shen, L., Shi, J.X., Shyn, S.I., Sigurdsson, E., Sinnamon, G.C.B., Smit, J.H., Smith, D.J., Streit, F., Strohmaier, J., Tansey, K.E., Teismann, H., Teumer, A., Thompson, W., Thomson, P.A., Thorgeirsson, T.E., Traylor, M., Treutlein, J., Trubetskoy, V., Uitterlinden, A.G., Umbricht, D., Auwera, S. van der, Hemert, A.M. van, Viktorin, A., Visscher, P.M., Wang, Y.P., Webb, B.T., Weinsheimer, S.M., Wellmann, J., Willemsen, G., Witt, S.H., Wu, Y., Xi, H.S., Yang, J., Zhang, F.T., Arolt, V., Baune, B.T., Berger, K., Boomsma, D.I., Cichon, S., Dannlowski, U., Geus, E.J.C. de, DePaulo, J.R., Domenici, E., Domschke, K., Esko, T., Grabe, H.J., Hamilton, S.P., Hayward, C., Heath, A.C., Kendler, K.S., Kloiber, S., Lewis, G., Li, Q.S., Lucae, S., Madden, P.A.F., Magnusson, P.K., Martin, N.G., McIntosh, A.M., Metspalu, A., Muller-Myhsok, B., Nothen, M.M., O'Donovan, M.C., Paciga, S.A., Pedersen, N.L., Penninx, B.W.J.H., Perlis, R.H., Porteous, D.J., Potash, J.B., Preisig, M., Rietschel, M., Schaefer, C., Schulze, T.G., Smoller, J.W., Tiemeier, H., Uher, R., Volzke, H., Weissman, M.M., Lewis, C.M., Levinson, D.F., Breen, G., Agee, M., Alipanahi, B., Auton, A., Bell, R.K., Bryc, K., Elson, S.L., Fontanillas, P., Furlotte, N.A., Hromatka, B.S., Huber, K.E., Kleinman, A., Litterman, N.K., McIntyre, M.H., Mountain, J.L., Noblin, E.S., Northover, C.A.M., Pitts, S.J., Sathirapongsasuti, J.F., Sazonova, O.V., Shelton, J.F., Shringarpure, S., Tung, J.Y., Vacic, V., Wilson, C.H., Psychiat Genomics Consortium, BUPGEN, 23andMe Re, Biological Psychology, APH - Methodology, APH - Health Behaviors & Chronic Diseases, APH - Personalized Medicine, APH - Mental Health, Complex Trait Genetics, Amsterdam Neuroscience - Complex Trait Genetics, Adult Psychiatry, Psychiatry, Human genetics, Amsterdam Reproduction & Development (AR&D), VU University medical center, APH - Digital Health, Aarno Palotie / Principal Investigator, Institute for Molecular Medicine Finland, Genomics of Neurological and Neuropsychiatric Disorders, Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Perceptual and Cognitive Neuroscience (PCN), Clinical Cognitive Neuropsychiatry Research Program (CCNP), Autism Spectrum Disorders Working Group of The Psychiatric Genomics Consortium, BUPGEN, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Me Research Team, Epidemiology, and Child and Adolescent Psychiatry / Psychology

Subjects
Male, Netherlands Twin Register (NTR), Multifactorial Inheritance, Autism Spectrum Disorder, Denmark, LD SCORE REGRESSION, LOCI, Genome-wide association study, DE-NOVO, 0302 clinical medicine, Polymorphism (computer science), Risk Factors, SYNAPTIC PLASTICITY, CELL-SURFACE, Child, Genetics, 0303 health sciences, HERITABILITY, Genetic Predisposition to Disease/genetics, 1184 Genetics, developmental biology, physiology, Polymorphism, Single Nucleotide/genetics, Phenotype, 3. Good health, Schizophrenia, Autism spectrum disorder, Child, Preschool, Genome-Wide Association Study/methods, Female, SIMONS SIMPLEX COLLECTION, Adolescent, Biology, NEURITE OUTGROWTH, Polymorphism, Single Nucleotide, behavioral disciplines and activities, Article, 03 medical and health sciences, mental disorders, medicine, Humans, Genetic Predisposition to Disease, GENOME-WIDE ASSOCIATION, SDG 2 - Zero Hunger, Multifactorial Inheritance/genetics, METAANALYSIS, 030304 developmental biology, Case-control study, Heritability, medicine.disease, Autism Spectrum Disorder/genetics, Case-Control Studies, 3111 Biomedicine, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract

Published in final edited form as: Nat Genet. 2019 March ; 51(3): 431–444. doi:10.1038/s41588-019-0344-8., Autism spectrum disorder (ASD) is a highly heritable and heterogeneous group of neurodevelopmental phenotypes diagnosed in more than 1% of children. Common genetic variants contribute substantially to ASD susceptibility, but to date no individual variants have been robustly associated with ASD. With a marked sample size increase from a unique Danish population resource, we report a genome-wide association meta-analysis of 18,381 ASD cases and 27,969 controls that identifies five genome-wide significant loci. Leveraging GWAS results from three phenotypes with significantly overlapping genetic architectures (schizophrenia, major depression, and educational attainment), seven additional loci shared with other traits are identified at equally strict significance levels. Dissecting the polygenic architecture, we find both quantitative and qualitative polygenic heterogeneity across ASD subtypes. These results highlight biological insights, particularly relating to neuronal function and corticogenesis and establish that GWAS performed at scale will be much more productive in the near term in ASD., The iPSYCH project is funded by the Lundbeck Foundation (grant numbers R102-A9118 and R155-2014-1724) and the universities and university hospitals of Aarhus and Copenhagen. Genotyping of iPSYCH and PGC samples was supported by grants from the Lundbeck Foundation, the Stanley Foundation, the Simons Foundation (SFARI 311789 to MJD), and NIMH (5U01MH094432–02 to MJD). The Danish National Biobank resource was supported by the Novo Nordisk Foundation. Data handling and analysis on the GenomeDK HPC facility was supported by NIMH (1U01MH109514–01 to M O’Donovan and ADB). High-performance computer capacity for handling and statistical analysis of iPSYCH data on the GenomeDK HPC facility was provided by the Centre for Integrative Sequencing, iSEQ, Aarhus University, Denmark (grant to ADB). Drs. S De Rubeis and JD Buxbaum were supported by NIH grants MH097849 (to JDB) and MH111661 (to JDB), and by the Seaver Foundation (to SDR and JDB). Dr J Martin was supported by the Wellcome Trust (grant no: 106047). O. Andreassen received funding from Research Council of Norway (#213694, #223273, #248980, #248778), Stiftelsen KG Jebsen and South-East Norway Health Authority. We thank the research participants and employees of 23andMe for making this work possible.

Published
2019

41. Genome-wide by environment interaction studies of depressive symptoms and psychosocial stress in UK Biobank and Generation Scotland

Author

Arnau-Soler, A., Macdonald-Dunlop, E., Adams, M.J., Clarke, T.K., MacIntyre, D.J., Milburn, K., Navrady, L., Hayward, C., McIntosh, A.M., Thomson, P.A., Wray, N.R., Ripke, S., Mattheisen, M., Trzaskowski, M., Byrne, E.M., Abdellaoui, A., Agerbo, E., Air, T.M., Andlauer, T.F.M., Bacanu, S.A., Baekvad-Hansen, M., Beekman, A.T.F., Bigdeli, T.B., Binder, E.B., Blackwood, D.H.R., Bryois, J., Buttenscon, H.N., Bybjerg-Grauholm, J., Cai, N., Castelao, E., Christensen, J.H., Coleman, J.R.I., Colodro-Conde, L., Couvy-Duchesne, B., Craddock, N., Rawford, G.E.C., Davies, G., Deary, I.J., Degenhardt, F., Derks, E.M., Direk, N., Dolan, C.V., Dunn, E.C., Eley, T.C., Escott-Price, V., Kiadeh, F.F.H., Finucane, H.K., Foo, J.C., Forstner, A.J., Frank, J., Gaspar, H.A., Gill, M., Goes, F.S., Gordon, S.D., Grove, J., Hall, L.S., Hansen, C.S., Hansen, T.F., Herms, S., Hickie, I.B., Hoffmann, P., Homuth, G., Horn, C., Hottenga, J.J., Hougaard, D.M., Ising, M., Jansen, R., Jones, I., Jones, L.A., Jorgenson, E., Knowles, J.A., Kohane, I.S., Kraft, J., Kretzschmar, W.W., Krogh, J., Kutalik, Z., Li, Y.H., Lind, P.A., Macintyre, D.J., MacKinnon, D.F., Maier, R.M., Maier, W., Marchini, J., Mbarek, H., McGrath, P., McGuffin, P., Medland, S.E., Mehta, D., Middeldorp, C.M., Mihailov, E., Milaneschi, Y., Milani, L., Mondimore, F.M., Montgomery, G.W., Mostafavi, S., Mullins, N., Nauck, M., Ng, B., Nivard, M.G., Nyholt, D.R., O'Reilly, P.F., Oskarsson, H., Owen, M.J., Painter, J.N., Pedersen, C.B., Pedersen, M.G., Peterson, R.E., Pettersson, E., Peyrot, W.J., Pistis, G., Posthuma, D., Quiroz, J.A., Qvist, P., Rice, J.P., Riley, B.P., Rivera, M., Mirza, S.S., Schoevers, R., Schulte, E.C., Shen, L., Shi, J.X., Shyn, S.I., Sigurdsson, E., Sinnamon, G.C.B., Smit, J.H., Smith, D.J., Stefansson, H., Steinberg, S., Streit, F., Strohmaier, J., Tansey, K.E., Teismann, H., Teumer, A., Thompson, W., Thorgeirsson, T.E., Traylor, M., Treutlein, J., Trubetskoy, V., Uitterlinden, A.G., Umbricht, D., Auwera, S. van der, Hemert, A.M. van, Viktorin, A., Visscher, P.M., Wang, Y.P., Webb, B.T., Weinsheimer, S.M., Wellmann, J., Willemsen, G., Witt, S.H., Wu, Y., Xi, H.L.S., Yang, J., Zhang, F.T., Arolt, V., Baune, B.T., Berger, K., Boomsma, D.I., Cichon, S., Dannlowski, U., Geus, E.J.C. de, DePaulo, J.R., Domenici, E., Domschke, K., Esko, T., Grabe, H.J., Hamilton, S.P., Heath, A.C., Kendler, K.S., Kloiber, S., Lewis, G., Li, Q.Q.S., Lucae, S., Madden, P.A.F., Magnusson, P.K., Martin, N.G., Metspalu, A., Mors, O., Mortensen, P.B., Muller-Myhsok, B., Nordentoft, M., Nothen, M.M., O'Donovan, M.C., Paciga, S.A., Pedersen, N.L., Penninx, B.W.J.H., Perlis, R.H., Porteous, D.J., Potash, J.B., Preisig, M., Rietschel, M., Schaefer, C., Schulze, T.G., Smoller, J.W., Stefansson, K., Tiemeier, H., Uher, R., Volzke, H., Weissman, M.M., Werge, T., Lewis, C.M., Levinson, D.F., Breen, G., Borglum, A.S.D., Sullivan, P.F., Generation Scotland, and Psychiat Genomics Consortium

Abstract

Stress is associated with poorer physical and mental health. To improve our understanding of this link, we performed genome-wide association studies (GWAS) of depressive symptoms and genome-wide by environment interaction studies (GWEIS) of depressive symptoms and stressful life events (SLE) in two UK population-based cohorts (Generation Scotland and UK Biobank). No SNP was individually significant in either GWAS, but gene-based tests identified six genes associated with depressive symptoms in UK Biobank (DCC, ACSS3, DRD2, STAG1, FOXP2 and KYNU; p < 2.77 x 10(-6)). Two SNPs with genome-wide significant GxE effects were identified by GWEIS in Generation Scotland: rs12789145 (53-kb downstream PIWIL4; p = 4.95 x 10(-9); total SLE) and rs17070072 (intronic to ZCCHC2; p = 1.46 x 10(-8); dependent SLE). A third locus upstream CYLC2 (rs12000047 and rs12005200, p < 2.00 x 10(-8); dependent SLE) when the joint effect of the SNP main and GxE effects was considered. GWEIS gene-based tests identified: MTNR1B with GxE effect with dependent SLE in Generation Scotland; and PHF2 with the joint effect in UK Biobank (p < 2.77 x 10(-6)). Polygenic risk scores (PRSs) analyses incorporating GxE effects improved the prediction of depressive symptom scores, when using weights derived from either the UK Biobank GWAS of depressive symptoms (p = 0.01) or the PGC GWAS of major depressive disorder (p = 5.91 x 10(-3)). Using an independent sample, PRS derived using GWEIS GxE effects provided evidence of shared aetiologies between depressive symptoms and schizotypal personality, heart disease and COPD. Further such studies are required and may result in improved treatments for depression and other stress-related conditions.

Published
2019

42. Evidence for increased genetic risk load for major depression in patients assigned to electroconvulsive therapy

Author

Foo, J.C., Streit, F., Frank, J., Witt, S.H., Treutlein, J., Baune, B.T., Moebus, S., Jockel, K.H., Forstner, A.J., Nothen, M.M., Rietschel, M., Sartorius, A., Kranaster, L., Wray, N.R., Ripke, S., Mattheisen, M., Trzaskowski, M., Byrne, E.M., Abdellaoui, A., Adams, M.J., Agerbo, E., Air, T.M., Andlauer, T.F.M., Bacanu, S.A., Baekvad-Hansen, M., Beekman, A.T.F., Bigdeli, T.B., Binder, E.B., Blackwood, D.H.R., Bryois, J., Buttenschon, H.N., Bybjerg-Grauholm, J., Cai, N., Castelao, E., Christensen, J.H., Clarke, T.K., Coleman, J.R.I., Colodro-Conde, L., Couvy-Duchesne, B., Craddock, N., Crawford, G.E., Davies, G., Deary, I.J., Degenhardt, F., Derks, E.M., Direk, N., Dolan, C.V., Dunn, E.C., Eley, T.C., Escott-Price, V., Kiadeh, F.F.H., Finucane, H.K., Gaspar, H.A., Gill, M., Goes, F.S., Gordon, S.D., Grove, J., Hall, L.S., Hansen, C.S., Hansen, T.F., Herms, S., Hickie, I.B., Hoffmann, P., Homuth, G., Horn, C., Hottenga, J.J., Hougaard, D.M., Ising, M., Jansen, R., Jones, I., Jones, L.A., Jorgenson, E., Knowles, J.A., Kohane, I.S., Kraft, J., Kretzschmar, W.W., Krogh, J., Kutalik, Z., Li, Y.H., Lind, P.A., MacIntyre, D.J., MacKinnon, D.F., Maier, R.M., Maier, W., Marchini, J., Mbarek, H., McGrath, P., McGuffin, P., Medland, S.E., Mehta, D., Middeldorp, C.M., Mihailov, E., Milaneschi, Y., Milani, L., Mondimore, F.M., Montgomery, G.W., Mostafavi, S., Mullins, N., Nauck, M., Ng, B., Nivard, M.G., Nyholt, D.R., O'Reilly, P.F., Oskarsson, H., Owen, M.J., Painter, J.N., Pedersen, C.B., Pedersen, M.G., Peterson, R.E., Pettersson, E., Peyrot, W.J., Pistis, G., Posthuma, D., Quiroz, J.A., Qvist, P., Rice, J.P., Riley, B.P., Rivera, M., Mirza, S.S., Schoevers, R., Schulte, E.C., Shen, L., Shi, J.X., Shyn, S.I., Sigurdsson, E., Sinnamon, G.C.B., Smit, J.H., Smith, D.J., Stefansson, H., Steinberg, S., Strohmaier, J., Tansey, K.E., Teismann, H., Teumer, A., Thompson, W., Thomson, P.A., Thorgeirsson, T.E., Traylor, M., Trubetskoy, V., Uitterlinden, A.G., Umbricht, D., Auwera, S. van der, Hemert, A.M. van, Viktorin, A., Visscher, P.M., Wang, Y., Webb, B.T., Weinsheimer, S.M., Wellmann, J., Willemsen, G., Wu, Y., Xi, H.L.S., Yang, J., Zhang, F.T., Arolt, V., Berger, K., Boomsma, D.I., Cichon, S., Dannlowski, U., Geus, E.J.C. de, DePaulo, J.R., Domenici, E., Domschke, K., Esko, T., Grabe, H.J., Hamilton, S.P., Hayward, C., Heath, A.C., Kendler, K.S., Kloiber, S., Lewis, G., Li, Q.Q.S., Lucae, S., Madden, P.A.F., Magnusson, P.K., Martin, N.G., McIntosh, A.M., Metspalu, A., Mors, O., Mortensen, P.B., Muller-Myhsok, B., Nordentoft, M., O'Donovan, M.C., Paciga, S.A., Pedersen, N.L., Penninx, B.W.J.H., Perlis, R.H., Porteous, D.J., Potash, J.B., Preisig, M., Schaefer, C., Schulze, T.G., Smoller, J.W., Stefansson, K., Tiemeier, H., Uher, R., Voelzke, H., Weissman, M.M., Werge, T., Lewis, C.M., Levinson, D.F., Breen, G., Borglum, A.D., Sullivan, P.F., and Major Depressive Disorder Worki

Subjects
treatment-resistance, polygenic risk scores, depression, major depression, electroconvulsive therapy
Abstract

Electroconvulsive therapy (ECT) is the treatment of choice for severe and treatment-resistantdepression; disorder severity and unfavorable treatment outcomes are shown to be influencedby an increased genetic burden for major depression (MD). Here, we tested whether ECT assign-ment and response/nonresponse are associated with an increased genetic burden for majordepression (MD) using polygenic risk score (PRS), which summarize the contribution of disease-related common risk variants. Fifty-one psychiatric inpatients suffering from a major depressiveepisode underwent ECT. MD-PRS were calculated for these inpatients and a separatepopulation-based sample (n = 3,547 healthy; n = 426 self-reported depression) based on sum-mary statistics from the Psychiatric Genomics Consortium MDD-working group (Cases:n = 59,851; Controls: n = 113,154). MD-PRS explained a significant proportion of disease statusbetween ECT patients and healthy controls (p = .022, R2 = 1.173%); patients showed higherMD-PRS. MD-PRS in population-based depression self-reporters were intermediate betweenECT patients and controls (n.s.). Significant associations between MD-PRS and ECT response(50% reduction in Hamilton depression rating scale scores) were not observed. Our findings indi-cate that ECT cohorts show an increased genetic burden for MD and are consistent with thehypothesis that treatment-resistant MD patients represent a subgroup with an increased geneticrisk for MD. Larger samples are needed to better substantiate these findings.

Published
2019

44. Bipolar multiplex families have an increased burden of common risk variants for psychiatric disorders

Author

Andlauer, T.F.M. (Till F. M.), Guzman-Parra, J. (Jose), Streit, F. (Fabian), Strohmaier, J. (Jana), González, M.J. (Maria José), Gil Flores, S. (Susana), Cabaleiro Fabeiro, F.J. (Francisco J.), del Río Noriega, F. (Francisco), Perez, F.P. (Fermin Perez), Haro González, J. (Jesus), Orozco Diaz, G. (Guillermo), Diego, Y. (Yolanda) de, Moreno-Küstner, B. (Berta), Auburger, G. (Georg), Degenhardt, F. (Franziska), Heilmann-Heimbach, S. (Stefanie), Herms, S. (Stefan), Hoffmann, P. (Per), Frank, J. (Josef), Foo, J.C. (Jerome C.), Treutlein, J. (Jens), Witt, S.H. (Stephanie H), Cichon, S. (Sven), Kogevinas, M. (Manolis), Stahl, E.A. (Eli A), Breen, G. (Gerome), Forstner, A.J. (Andreas J), McQuillin, A. (Andrew), Ripke, S. (Stephan), Trubetskoy, V. (Vassily), Mattheisen, M. (Manuel), Wang, Y. (Yunpeng), Coleman, J.R.I. (Jonathan R I), Gaspar, H.A. (Héléna A), Leeuw, C. (Christiaan) de, Steinberg, S. (Stacy), Pavlides, J.M.W. (Jennifer M Whitehead), Trzaskowski, M. (Maciej), Pers, T.H. (Tune H), Holmans, P.A. (Peter A.), Abbott, L. (Liam), Agerbo, E. (Esben), Akil, H. (Huda), Albani, D. (Diego), Alliey-Rodriguez, N. (Ney), Als, T.D. (Thomas D), Anjorin, A. (Adebayo), Antilla, V. (Verneri), Awasthi, S. (Swapnil), Badner, J.A. (Judith A), Bækvad-Hansen, M. (Marie), Barchas, J.D. (Jack D), Bass, N. (Nicholas), Bauer, M. (Michael), Belliveau, R.A. (Richard A.), Bergen, S.E. (Sarah), Pedersen, C.B. (C.), Bøen, E. (Erlend), Boks, M.P.M. (Marco), Boocock, J. (James), Budde, M. (Monika), Bunney, W.E. (William E), Burmeister, M., Bybjerg-Grauholm, J. (Jonas), Byerley, W.F. (William F), Casas, M. (Miquel), Cerrato, F. (Felecia), Cervantes, P. (Pablo), Chambert, K. (Kimberly), Charney, A.W. (Alexander W), Chen, D. (Danfeng), Churchhouse, C. (Claire), Clarke, T.-K. (Toni-Kim), Coryell, W.H. (William H), Craig, D.W. (David W), Cruceanu, C. (Cristiana), Czerski, P.M., Dale, A.M. (Anders), de Jong, S. (Simone), Del-Favero, J. (Jurgen), DePaulo, J.R. (J Raymond), Djurovic, S. (Srdjan), Dobbyn, A.L. (Amanda L), Dumont, A. (Ashley), Elvsåshagen, T. (Torbjørn), Escott-Price, V. (Valentina), Fan, C.C. (Chun Chieh), Fischer, S.B. (Sascha B), Flickinger, M. (Matthew), Foroud, T.M. (Tatiana M), Forty, L. (Liz), Fraser, C. (Christine), Luben, R.N. (Robert), Frisén, L. (Louise), Gade, K. (Katrin), Gage, D. (Diane), Garnham, J. (Julie), Giambartolomei, C. (Claudia), Pedersen, M.G. (Marianne Giørtz), Goldstein, J.I. (Jacqueline), Gordon, S.D. (Scott D), Gordon-Smith, K. (Katherine), Green, E.K. (Elaine K), Green, M.J. (Melissa J), Greenwood, T.A. (Tiffany A), Grove, J. (Jakob), Guan, W. (Weihua), Parra, J.G. (José Guzman), Hamshere, M.L. (Marian), Hautzinger, M. (Martin), Heilbronner, U. (Urs), Hipolito, M. (Maria), Holland, D. (Dominic), Huckins, L. (Laura), Jamain, S. (Stéphane), Johnson, J.S. (Jessica S), Juréus, A. (Anders), Kandaswamy, R. (Radhika), Karlsson, R. (Robert), Kennedy, J.L. (James L), Kittel-Schneider, S. (Sarah), Knowles, J.A. (James A), Koller, A.C. (Anna C), Kupka, R.W. (Ralph ), Lavebratt, C. (Catharina), Lawrence, J. (Jacob), Lawson, W.B. (William B), Leber, I. (Isabelle), Lee, P.H. (Phil H), Levy, S.E. (Shawn E), Li, J.Z. (Jun Z), Liu, C. (Chunyu), Lucae, S. (Susanne), Maaser, A. (Anna), Macintyre, D.J. (Donald J), Mahon, P.B. (Pamela B), Maier, W. (Wolfgang), Martinsson, L. (Lina), McCarroll, S.A. (Steve), McGuffin, P. (Peter), Mcinnis, M.G. (Melvin G), McKay, J.D. (James D), Medeiros, H. (Helena), Medland, S.E. (Sarah E), Meng, F. (Fan), Milani, L. (Lili), Montgomery, G.W. (Grant W), Morris, D.W. (Derek W), Mühleisen, T.W. (Thomas W), Mullins, N. (Niamh), Nguyen, H. (Hoang), Nievergelt, C.M. (Caroline M), Adolfsson, A.N. (Annelie Nordin), Nwulia, E.A. (Evaristus A), O’Donovan, C. (Claire), Loohuis, L.M.O. (Loes M Olde), Ori, A.P.S. (Anil P S), Oruc, L. (Lilijana), Ösby, U. (Urban), Perlis, R.H. (Roy H), Perry, A. (Amy), Pfennig, A. (Andrea), Potash, J.B. (James B), Purcell, S.M. (Shaun M), Regeer, E.J. (Eline Janet), Reif, A. (Andreas), Reinbold, C.S. (Céline S), Rice, J.P. (John), Richards, A. (Alex), Rivas, F. (Fabio), Rivera, M. (Margarita), Roussos, A. (Alexandra), Ruderfer, D. (Douglas), Ryu, J. (Julie), Sánchez-Mora, C. (Cristina), Schatzberg, A.F. (Alan F), Scheftner, W.A. (William A), Schork, N.J. (Nicholas), Weickert, C.S. (Cynthia Shannon), Shehktman, T. (Tatyana), Shilling, P.D. (Paul D), Sigurdsson, E. (Engilbert), Slaney, C. (Claire), Smeland, O.B. (Olav B), Sobell, J.L. (Janet L), Hansen, C.S. (Christine Søholm), Spijker, A.T. (Anne T), Clair, D.S., Steffens, M. (Michael), Strauss, J.S. (John S), Szelinger, S. (Szabolcs), Thompson, R.C. (Robert C), EThorgeirsson, T. (Thorgeir), Vedde, H. (Helmut), Wang, W. (Weiqing), Watson, S.J. (Stanley J), Weickert, T.W. (Thomas W), Xi, S. (Simon), Xu, W. (Wei), Young, A.H. (Allan H), Zandi, P.P. (Peter P), Zhang, P. (Ping), Zöllner, S. (Sebastian), Adolfsson, R., Agartz, I. (Ingrid), Alda, M. (Martin), Backlund, L. (Lena), Baune, B.T. (Bernhard T), Bellivier, F. (Frank), Berrettini, W. (Wade), Biernacka, J.M. (Joanna M), Blackwood, D.H.R. (Douglas), Boehnke, M. (Michael), Børglum, A.D. (Anders D), Corvin, A. (Aiden), Craddock, N. (Nicholas), Daly, M.J. (Mark), Dannlowski, U. (Udo), Esko, T. (Tõnu), Etain, B. (Bruno), Frye, M.A. (Mark A), Fullerton, J.M. (Janice M), Gershon, E.S. (Elliot S), Gill, M. (Michael), Goes, F. (Fernando), Grigoroiu-Serbanescu, M. (Maria), Hauser, J. (J.), Hougaard, D.M. (David M), Hultman, C.M. (Christina), Jones, I. (Ian), Jones, L.A. (Lisa A), Kahn, R. (René), Kirov, G. (George), Landén, M. (Mikael), Leboyer, M. (Marion), Lewis, C.M. (Cathryn), Li, Q.S. (Qingqin S), Lissowska, J. (Jolanta), Martin, N.G. (Nicholas), Mayoral, F. (Fermin), McElroy, S.L. (Susan L), McIntosh, A.M. (Andrew), Mcmahon, F.J. (Francis J), Melle, I. (Ingrid), Metspalu, A. (Andres), Mitchell, P.B. (Philip B), Morken, G. (Gunnar), Mors, O. (Ole), Mortensen, P.B. (Preben Bo), Müller-Myhsok, B. (Bertram), Myers, R.H. (Richard), Neale, B.M. (Benjamin), Nimgaonkar, V. (Vishwajit), Nordentoft, M. (Merete), Nöthen, M.M. (Markus), O’Donovan, M.C. (Michael C), Oedegaard, K.J. (Ketil J), Owen, M.J. (Michael J), Paciga, S.A. (Sara A), Pato, C. (Carlos), Posthuma, D. (Danielle), Ramos-Quiroga, J.A. (Josep Antoni), Ribasés, M. (Marta), Rietschel, M. (Marcella), Rouleau, G.A. (Guy A), Schalling, M. (Martin), Schofield, P.R. (Peter R), Schulze, T.G. (Thomas G), Serretti, A. (Alessandro), Smoller, J.W., Stefansson, H. (Hreinn), Zwart, J-A. (John-Anker), Stordal, E. (Eystein), Sullivan, P.F. (Patrick F), Turecki, G. (Gustavo), Vaaler, A.E. (Arne E), Vieta, E. (Eduard), Vincent, J.B. (John B), Werge, T.M. (Thomas), Nurnberger, J.I. (John I), Wray, N.R. (Naomi), Florio, A.D. (Arianna Di), Edenberg, H.J. (Howard), Ophoff, R.A. (Roel), Scott, L.J. (Laura J), Andreassen, O.A. (Ole), Kelsoe, J.R. (John), Sklar, P. (Pamela), Wray, N.R. (Naomi R), Byrne, E.M. (Enda), Abdellaoui, A. (Abdel), Adams, M.J. (Mark J), Air, T.M. (Tracy M), Bacanu, S.A. (Silviu), Beekman, A.T.F. (Aartjan), Bigdeli, T.B. (Tim B), Binder, E.B. (Elisabeth), Bryois, J. (Julien), Buttenschøn, H.N. (Henriette N), Cai, N. (Na), Castelao, E. (Enrique), Christensen, J.H. (Jane Hvarregaard), Clarke, T.-K., Colodro-Conde, L. (Lucía), Couvy-Duchesne, B. (Baptiste), Craddock, N.J. (Nick), Crawford, G.E. (Gregory E), Davies, G. (Gail), Deary, I.J. (Ian J), Degenhardt, F., Derks, E.M. (Eske M), Direk, N. (Nese), Dolan, C.V. (Conor), Dunn, E.C. (Erin C.), Eley, T.C. (T.), Kiadeh, F.F.H. (Farnush Farhadi Hassan), Finucane, H.K. (Hilary K), Foo, J.C. (Jerome C), Goes, F.S. (Fernando S), Gordon, S.D. (Scott D.), Hall, L.S. (Lynsey S), Hansen, T.F. (Thomas F), Hickie, I.B. (Ian), Homuth, G. (Georg), Horn, C. (Carsten), Hottenga, J.J. (Jouke Jan), Hougaard, D.M. (David), Howard, D.M. (David M), Ising, M. (Marcus), Jansen, R. (Rick), Jones, I., Jones, L. (Louisa), Jorgenson, E. (Eric), Kohane, I.S. (Isaac S), Kraft, J. (Julia), Kretzschmar, W.W. (Warren W.), Kutalik, Z. (Zoltán), Li, Y. (Yihan), Lind, P.A. (Penelope), MacIntyre, D.J. (Donald J), MacKinnon, D.F. (Dean F), Maier, R.M. (Robert M), Marchini, J. (Jonathan), Mbarek, H., McGrath, P. (Patrick), Mcguffin, P. (Peter), Medland, S.E. (Sarah), Mehta, D. (Divya), Middeldorp, C.M. (Christel M), Mihailov, E. (Evelin), Milaneschi, Y. (Yuri), Mondimore, F.M. (Francis M), Montgomery, G.W. (Grant), Mostafavi, S. (Sara), Nauck, M. (Matthias), Ng, B. (Bernard), Nivard, M. (Michel), Nyholt, D.R. (Dale), O’Reilly, P.F. (Paul F), Oskarsson, H. (Hogni), Owen, M.J. (Michael), Painter, J.N. (Jodie N.), Pedersen, C.B. (Carsten Bøcker), Peterson, R.E. (Roseann E), Pettersson, E. (Erik), Peyrot, W.J. (Wouter ), Pistis, G. (Giorgio), Quiroz, J.A. (Jorge A), Qvist, P. (Per), Rice, J.P. (John P), Riley, B.P. (Brien P.), Mirza, S.S. (Saira), Schoevers, R. (Robert), Schulte, E.C. (Eva C), Shen, L. (Li), Shi, J. (Jianxin), Shyn, S.I. (Stanley I), Sinnamon, G.C.B. (Grant C B), Smith, A.V. (Davey), Smith, D.J. (Daniel J), Tansey, K.E., Teismann, H. (Henning), Teumer, A. (Alexander), Thompson, W.K. (Wesley K.), Thomson, P.A. (Pippa A), Thorgeirsson, T.E. (Thorgeir E), Traylor, M. (Matthew), Uitterlinden, A.G. (André), Umbricht, D. (Daniel), Van der Auwera, S. (Sandra), van Hemert, A.M. (Albert M), Viktorin, A. (Alexander), Visscher, P.M. (Peter M), Webb, B.T. (Bradley T.), Weinsheimer, S.M. (Shantel Marie), Wellmann, J. (Jürgen), Willemsen, G.A.H.M. (Gonneke), Wu, Y. (Yang), Xi, H.S. (Hualin S), Yang, J. (Joanna), Zhang, F. (Futao), Arolt, V. (Volker), Baune, B.T., Berger, K. (Klaus), Boomsma, D.I. (Dorret), Geus, E.J.C. (Eco) de, Domenici, E. (Enrico), Domschke, K. (Katharina), Grabe, H.J. (Hans Jörgen), Hamilton, S.P. (Steven P), Hayward, C. (Caroline), Heath, A.C. (Andrew), Jablensky, A. (Assen), Kloiber, S. (Stefan), Lewis, G., Madden, P.A. (Pamela), Magnusson, P.K. (Patrik), Martin, N.G. (Nicholas G), McIntosh, A.M. (Andrew M), Mors, O., Müller-Myhsok, B. (B.), Nöthen, M.M. (Markus M), Pedersen, N.L. (Nancy), Penninx, B.W.J.H. (Brenda), Porteous, D.J. (David J.), Preisig, M. (Martin), Schaefer, C. (Catherine), Smoller, J.W. (Jordan W), Stefansson, K. (Kari), Tiemeier, H.W. (Henning), Uher, R. (Rudolf), Völzke, H. (Henry), Weissman, M.M., Werge, T. (Thomas), Lewis, C.M. (Cathryn M), Levinson, D.F. (Douglas F.), Borglum, A.D. (Anders), Sullivan, P.F. (Patrick), Mayoral, F. (Fermín), Muller-Myhsok, B. (B.), Forstner, A.J. (Andreas J.), Nöthen, M.M. (Markus M.), Andlauer, T.F.M. (Till F. M.), Guzman-Parra, J. (Jose), Streit, F. (Fabian), Strohmaier, J. (Jana), González, M.J. (Maria José), Gil Flores, S. (Susana), Cabaleiro Fabeiro, F.J. (Francisco J.), del Río Noriega, F. (Francisco), Perez, F.P. (Fermin Perez), Haro González, J. (Jesus), Orozco Diaz, G. (Guillermo), Diego, Y. (Yolanda) de, Moreno-Küstner, B. (Berta), Auburger, G. (Georg), Degenhardt, F. (Franziska), Heilmann-Heimbach, S. (Stefanie), Herms, S. (Stefan), Hoffmann, P. (Per), Frank, J. (Josef), Foo, J.C. (Jerome C.), Treutlein, J. (Jens), Witt, S.H. (Stephanie H), Cichon, S. (Sven), Kogevinas, M. (Manolis), Stahl, E.A. (Eli A), Breen, G. (Gerome), Forstner, A.J. (Andreas J), McQuillin, A. (Andrew), Ripke, S. (Stephan), Trubetskoy, V. (Vassily), Mattheisen, M. (Manuel), Wang, Y. (Yunpeng), Coleman, J.R.I. (Jonathan R I), Gaspar, H.A. (Héléna A), Leeuw, C. (Christiaan) de, Steinberg, S. (Stacy), Pavlides, J.M.W. (Jennifer M Whitehead), Trzaskowski, M. (Maciej), Pers, T.H. (Tune H), Holmans, P.A. (Peter A.), Abbott, L. (Liam), Agerbo, E. (Esben), Akil, H. (Huda), Albani, D. (Diego), Alliey-Rodriguez, N. (Ney), Als, T.D. (Thomas D), Anjorin, A. (Adebayo), Antilla, V. (Verneri), Awasthi, S. (Swapnil), Badner, J.A. (Judith A), Bækvad-Hansen, M. (Marie), Barchas, J.D. (Jack D), Bass, N. (Nicholas), Bauer, M. (Michael), Belliveau, R.A. (Richard A.), Bergen, S.E. (Sarah), Pedersen, C.B. (C.), Bøen, E. (Erlend), Boks, M.P.M. (Marco), Boocock, J. (James), Budde, M. (Monika), Bunney, W.E. (William E), Burmeister, M., Bybjerg-Grauholm, J. (Jonas), Byerley, W.F. (William F), Casas, M. (Miquel), Cerrato, F. (Felecia), Cervantes, P. (Pablo), Chambert, K. (Kimberly), Charney, A.W. (Alexander W), Chen, D. (Danfeng), Churchhouse, C. (Claire), Clarke, T.-K. (Toni-Kim), Coryell, W.H. (William H), Craig, D.W. (David W), Cruceanu, C. (Cristiana), Czerski, P.M., Dale, A.M. (Anders), de Jong, S. (Simone), Del-Favero, J. (Jurgen), DePaulo, J.R. (J Raymond), Djurovic, S. (Srdjan), Dobbyn, A.L. (Amanda L), Dumont, A. (Ashley), Elvsåshagen, T. (Torbjørn), Escott-Price, V. (Valentina), Fan, C.C. (Chun Chieh), Fischer, S.B. (Sascha B), Flickinger, M. (Matthew), Foroud, T.M. (Tatiana M), Forty, L. (Liz), Fraser, C. (Christine), Luben, R.N. (Robert), Frisén, L. (Louise), Gade, K. (Katrin), Gage, D. (Diane), Garnham, J. (Julie), Giambartolomei, C. (Claudia), Pedersen, M.G. (Marianne Giørtz), Goldstein, J.I. (Jacqueline), Gordon, S.D. (Scott D), Gordon-Smith, K. (Katherine), Green, E.K. (Elaine K), Green, M.J. (Melissa J), Greenwood, T.A. (Tiffany A), Grove, J. (Jakob), Guan, W. (Weihua), Parra, J.G. (José Guzman), Hamshere, M.L. (Marian), Hautzinger, M. (Martin), Heilbronner, U. (Urs), Hipolito, M. (Maria), Holland, D. (Dominic), Huckins, L. (Laura), Jamain, S. (Stéphane), Johnson, J.S. (Jessica S), Juréus, A. (Anders), Kandaswamy, R. (Radhika), Karlsson, R. (Robert), Kennedy, J.L. (James L), Kittel-Schneider, S. (Sarah), Knowles, J.A. (James A), Koller, A.C. (Anna C), Kupka, R.W. (Ralph ), Lavebratt, C. (Catharina), Lawrence, J. (Jacob), Lawson, W.B. (William B), Leber, I. (Isabelle), Lee, P.H. (Phil H), Levy, S.E. (Shawn E), Li, J.Z. (Jun Z), Liu, C. (Chunyu), Lucae, S. (Susanne), Maaser, A. (Anna), Macintyre, D.J. (Donald J), Mahon, P.B. (Pamela B), Maier, W. (Wolfgang), Martinsson, L. (Lina), McCarroll, S.A. (Steve), McGuffin, P. (Peter), Mcinnis, M.G. (Melvin G), McKay, J.D. (James D), Medeiros, H. (Helena), Medland, S.E. (Sarah E), Meng, F. (Fan), Milani, L. (Lili), Montgomery, G.W. (Grant W), Morris, D.W. (Derek W), Mühleisen, T.W. (Thomas W), Mullins, N. (Niamh), Nguyen, H. (Hoang), Nievergelt, C.M. (Caroline M), Adolfsson, A.N. (Annelie Nordin), Nwulia, E.A. (Evaristus A), O’Donovan, C. (Claire), Loohuis, L.M.O. (Loes M Olde), Ori, A.P.S. (Anil P S), Oruc, L. (Lilijana), Ösby, U. (Urban), Perlis, R.H. (Roy H), Perry, A. (Amy), Pfennig, A. (Andrea), Potash, J.B. (James B), Purcell, S.M. (Shaun M), Regeer, E.J. (Eline Janet), Reif, A. (Andreas), Reinbold, C.S. (Céline S), Rice, J.P. (John), Richards, A. (Alex), Rivas, F. (Fabio), Rivera, M. (Margarita), Roussos, A. (Alexandra), Ruderfer, D. (Douglas), Ryu, J. (Julie), Sánchez-Mora, C. (Cristina), Schatzberg, A.F. (Alan F), Scheftner, W.A. (William A), Schork, N.J. (Nicholas), Weickert, C.S. (Cynthia Shannon), Shehktman, T. (Tatyana), Shilling, P.D. (Paul D), Sigurdsson, E. (Engilbert), Slaney, C. (Claire), Smeland, O.B. (Olav B), Sobell, J.L. (Janet L), Hansen, C.S. (Christine Søholm), Spijker, A.T. (Anne T), Clair, D.S., Steffens, M. (Michael), Strauss, J.S. (John S), Szelinger, S. (Szabolcs), Thompson, R.C. (Robert C), EThorgeirsson, T. (Thorgeir), Vedde, H. (Helmut), Wang, W. (Weiqing), Watson, S.J. (Stanley J), Weickert, T.W. (Thomas W), Xi, S. (Simon), Xu, W. (Wei), Young, A.H. (Allan H), Zandi, P.P. (Peter P), Zhang, P. (Ping), Zöllner, S. (Sebastian), Adolfsson, R., Agartz, I. (Ingrid), Alda, M. (Martin), Backlund, L. (Lena), Baune, B.T. (Bernhard T), Bellivier, F. (Frank), Berrettini, W. (Wade), Biernacka, J.M. (Joanna M), Blackwood, D.H.R. (Douglas), Boehnke, M. (Michael), Børglum, A.D. (Anders D), Corvin, A. (Aiden), Craddock, N. (Nicholas), Daly, M.J. (Mark), Dannlowski, U. (Udo), Esko, T. (Tõnu), Etain, B. (Bruno), Frye, M.A. (Mark A), Fullerton, J.M. (Janice M), Gershon, E.S. (Elliot S), Gill, M. (Michael), Goes, F. (Fernando), Grigoroiu-Serbanescu, M. (Maria), Hauser, J. (J.), Hougaard, D.M. (David M), Hultman, C.M. (Christina), Jones, I. (Ian), Jones, L.A. (Lisa A), Kahn, R. (René), Kirov, G. (George), Landén, M. (Mikael), Leboyer, M. (Marion), Lewis, C.M. (Cathryn), Li, Q.S. (Qingqin S), Lissowska, J. (Jolanta), Martin, N.G. (Nicholas), Mayoral, F. (Fermin), McElroy, S.L. (Susan L), McIntosh, A.M. (Andrew), Mcmahon, F.J. (Francis J), Melle, I. (Ingrid), Metspalu, A. (Andres), Mitchell, P.B. (Philip B), Morken, G. (Gunnar), Mors, O. (Ole), Mortensen, P.B. (Preben Bo), Müller-Myhsok, B. (Bertram), Myers, R.H. (Richard), Neale, B.M. (Benjamin), Nimgaonkar, V. (Vishwajit), Nordentoft, M. (Merete), Nöthen, M.M. (Markus), O’Donovan, M.C. (Michael C), Oedegaard, K.J. (Ketil J), Owen, M.J. (Michael J), Paciga, S.A. (Sara A), Pato, C. (Carlos), Posthuma, D. (Danielle), Ramos-Quiroga, J.A. (Josep Antoni), Ribasés, M. (Marta), Rietschel, M. (Marcella), Rouleau, G.A. (Guy A), Schalling, M. (Martin), Schofield, P.R. (Peter R), Schulze, T.G. (Thomas G), Serretti, A. (Alessandro), Smoller, J.W., Stefansson, H. (Hreinn), Zwart, J-A. (John-Anker), Stordal, E. (Eystein), Sullivan, P.F. (Patrick F), Turecki, G. (Gustavo), Vaaler, A.E. (Arne E), Vieta, E. (Eduard), Vincent, J.B. (John B), Werge, T.M. (Thomas), Nurnberger, J.I. (John I), Wray, N.R. (Naomi), Florio, A.D. (Arianna Di), Edenberg, H.J. (Howard), Ophoff, R.A. (Roel), Scott, L.J. (Laura J), Andreassen, O.A. (Ole), Kelsoe, J.R. (John), Sklar, P. (Pamela), Wray, N.R. (Naomi R), Byrne, E.M. (Enda), Abdellaoui, A. (Abdel), Adams, M.J. (Mark J), Air, T.M. (Tracy M), Bacanu, S.A. (Silviu), Beekman, A.T.F. (Aartjan), Bigdeli, T.B. (Tim B), Binder, E.B. (Elisabeth), Bryois, J. (Julien), Buttenschøn, H.N. (Henriette N), Cai, N. (Na), Castelao, E. (Enrique), Christensen, J.H. (Jane Hvarregaard), Clarke, T.-K., Colodro-Conde, L. (Lucía), Couvy-Duchesne, B. (Baptiste), Craddock, N.J. (Nick), Crawford, G.E. (Gregory E), Davies, G. (Gail), Deary, I.J. (Ian J), Degenhardt, F., Derks, E.M. (Eske M), Direk, N. (Nese), Dolan, C.V. (Conor), Dunn, E.C. (Erin C.), Eley, T.C. (T.), Kiadeh, F.F.H. (Farnush Farhadi Hassan), Finucane, H.K. (Hilary K), Foo, J.C. (Jerome C), Goes, F.S. (Fernando S), Gordon, S.D. (Scott D.), Hall, L.S. (Lynsey S), Hansen, T.F. (Thomas F), Hickie, I.B. (Ian), Homuth, G. (Georg), Horn, C. (Carsten), Hottenga, J.J. (Jouke Jan), Hougaard, D.M. (David), Howard, D.M. (David M), Ising, M. (Marcus), Jansen, R. (Rick), Jones, I., Jones, L. (Louisa), Jorgenson, E. (Eric), Kohane, I.S. (Isaac S), Kraft, J. (Julia), Kretzschmar, W.W. (Warren W.), Kutalik, Z. (Zoltán), Li, Y. (Yihan), Lind, P.A. (Penelope), MacIntyre, D.J. (Donald J), MacKinnon, D.F. (Dean F), Maier, R.M. (Robert M), Marchini, J. (Jonathan), Mbarek, H., McGrath, P. (Patrick), Mcguffin, P. (Peter), Medland, S.E. (Sarah), Mehta, D. (Divya), Middeldorp, C.M. (Christel M), Mihailov, E. (Evelin), Milaneschi, Y. (Yuri), Mondimore, F.M. (Francis M), Montgomery, G.W. (Grant), Mostafavi, S. (Sara), Nauck, M. (Matthias), Ng, B. (Bernard), Nivard, M. (Michel), Nyholt, D.R. (Dale), O’Reilly, P.F. (Paul F), Oskarsson, H. (Hogni), Owen, M.J. (Michael), Painter, J.N. (Jodie N.), Pedersen, C.B. (Carsten Bøcker), Peterson, R.E. (Roseann E), Pettersson, E. (Erik), Peyrot, W.J. (Wouter ), Pistis, G. (Giorgio), Quiroz, J.A. (Jorge A), Qvist, P. (Per), Rice, J.P. (John P), Riley, B.P. (Brien P.), Mirza, S.S. (Saira), Schoevers, R. (Robert), Schulte, E.C. (Eva C), Shen, L. (Li), Shi, J. (Jianxin), Shyn, S.I. (Stanley I), Sinnamon, G.C.B. (Grant C B), Smith, A.V. (Davey), Smith, D.J. (Daniel J), Tansey, K.E., Teismann, H. (Henning), Teumer, A. (Alexander), Thompson, W.K. (Wesley K.), Thomson, P.A. (Pippa A), Thorgeirsson, T.E. (Thorgeir E), Traylor, M. (Matthew), Uitterlinden, A.G. (André), Umbricht, D. (Daniel), Van der Auwera, S. (Sandra), van Hemert, A.M. (Albert M), Viktorin, A. (Alexander), Visscher, P.M. (Peter M), Webb, B.T. (Bradley T.), Weinsheimer, S.M. (Shantel Marie), Wellmann, J. (Jürgen), Willemsen, G.A.H.M. (Gonneke), Wu, Y. (Yang), Xi, H.S. (Hualin S), Yang, J. (Joanna), Zhang, F. (Futao), Arolt, V. (Volker), Baune, B.T., Berger, K. (Klaus), Boomsma, D.I. (Dorret), Geus, E.J.C. (Eco) de, Domenici, E. (Enrico), Domschke, K. (Katharina), Grabe, H.J. (Hans Jörgen), Hamilton, S.P. (Steven P), Hayward, C. (Caroline), Heath, A.C. (Andrew), Jablensky, A. (Assen), Kloiber, S. (Stefan), Lewis, G., Madden, P.A. (Pamela), Magnusson, P.K. (Patrik), Martin, N.G. (Nicholas G), McIntosh, A.M. (Andrew M), Mors, O., Müller-Myhsok, B. (B.), Nöthen, M.M. (Markus M), Pedersen, N.L. (Nancy), Penninx, B.W.J.H. (Brenda), Porteous, D.J. (David J.), Preisig, M. (Martin), Schaefer, C. (Catherine), Smoller, J.W. (Jordan W), Stefansson, K. (Kari), Tiemeier, H.W. (Henning), Uher, R. (Rudolf), Völzke, H. (Henry), Weissman, M.M., Werge, T. (Thomas), Lewis, C.M. (Cathryn M), Levinson, D.F. (Douglas F.), Borglum, A.D. (Anders), Sullivan, P.F. (Patrick), Mayoral, F. (Fermín), Muller-Myhsok, B. (B.), Forstner, A.J. (Andreas J.), and Nöthen, M.M. (Markus M.)

Abstract

Multiplex families with a high prevalence of a psychiatric disorder are often examined to identify rare genetic variants with large effect sizes. In the present study, we analysed whether the risk for bipolar disorder (BD) in BD multiplex families is influenced by common genetic variants. Furthermore, we investigated whether this risk is conferred mainly by BD-specific risk variants or by variants also associated with the susceptibility to schizophrenia or major depression. In total, 395 individuals from 33 Andalusian BD multiplex families (166 BD, 78 major depressive disorder, 151 unaffected) as well as 438 subjects from an independent, BD case/control cohort (161 unrelated BD, 277 unrelated controls) were analysed. Polygenic risk scores (PRS) for BD, schizophrenia (SCZ), and major depression were calculated and compared between the cohorts. Both the familial BD cases and unaffected family members had higher PRS for all three psychiatric disorders than the independent controls, with BD and SCZ being significant after correction for multiple testing, suggesting a high baseline risk for several psychiatric disorders in the families. Moreover, familial BD cases showed significantly higher BD PRS than unaffected family members and unrelated BD cases. A plausible hypothesis is that, in multiplex families with a general increase in risk for psychiatric disease, BD development is attributable to a high burden of common variants that confer a specific risk for BD. The present analyses demonstrated that common genetic risk variants for psychiatric disorders are likely to contribute to the high incidence of affective psychiatric disorders in the multiplex families. However, the PRS explained only part of the observed phenotypic variance, and rare variants might have also contributed to disease development.

Published
2019
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45. Classical Human Leukocyte Antigen Alleles and C4 Haplotypes Are Not Significantly Associated With Depression

Author

Glanville, K.P. (Kylie P.), Coleman, J.R.I. (Jonathan R.I.), Hanscombe, K.B. (Ken B.), Euesden, J. (Jack), Choi, S.W. (Shing Wan), Purves, K.L. (Kirstin L.), Breen, G. (Gerome), Air, T.M. (Tracy M.), Andlauer, T.F.M. (Till F.M.), Baune, B.T., Binder, E.B. (Elisabeth), Blackwood, D.H.R. (Douglas), Boomsma, D.I. (Dorret), Buttenschøn, H.N. (Henriette N.), Colodro-Conde, L. (Lucía), Dannlowski, U. (Udo), Direk, N. (Nese), Dunn, E.C. (Erin C.), Forstner, A.J. (Andreas J.), Geus, E.J.C. (Eco) de, Grabe, H.J. (Hans Jörgen), Hamilton, S.P. (Steven P), Jones, I., Jones, L. (Louisa), Knowles, J.A. (James A), Kutalik, Z. (Zoltán), Levinson, D.F. (Douglas F.), Lewis, G., Lind, P.A. (Penelope), Lucae, S. (Susanne), Magnusson, P.K. (Patrik), McGuffin, P. (Peter), McIntosh, A.M. (Andrew), Milaneschi, Y. (Yuri), Mors, O., Mostafavi, S. (Sara), Müller-Myhsok, B. (B.), Pedersen, N.L. (Nancy), Penninx, B.W.J.H. (Brenda), Potash, J.B. (James B), Preisig, M. (Martin), Ripke, S. (Stephan), Shi, J. (Jianxin), Shyn, S.I. (Stanley I), Smoller, J.W., Streit, F. (Fabian), Sullivan, P.F. (Patrick), Tiemeier, H.W. (Henning), Uher, R. (Rudolf), Van der Auwera, S. (Sandra), Weissman, M.M., Wray, N.R. (Naomi), Mattheisen, M. (Manuel), Trzaskowski, M. (Maciej), Byrne, E.M. (Enda), Abdellaoui, A. (Abdel), Adams, M.J. (Mark J.), Agerbo, E. (Esben), Bacanu, S.A. (Silviu), Bækvad-Hansen, M. (Marie), Beekman, A.T.F. (Aartjan), Bigdeli, T.B. (Tim B.), Bryois, J. (Julien), Bybjerg-Grauholm, J. (Jonas), Cai, N. (Na), Castelao, E. (Enrique), Christensen, J.H. (Jane Hvarregaard), Clarke, T.-K., Couvy-Duchesne, B. (Baptiste), Craddock, N.J. (Nick), Crawford, G.E. (Gregory E.), Davies, G. (Gail), Deary, I.J. (Ian J.), Degenhardt, F., Derks, E.M. (Eske), Dolan, C.V. (Conor), Eley, T.C. (T.), Escott-Price, V. (Valentina), Hassan Kiadeh, F.F. (Farnush Farhadi), Finucane, H.K. (Hilary K.), Foo, J.C. (Jerome C.), Frank, J. (Josef), Gaspar, H.A. (Héléna A.), Gill, M. (Michael), Goes, F.S. (Fernando S.), Gordon, S.D. (Scott D.), Grove, J. (Jakob), Hall, L.S. (Lynsey S.), Hansen, C.S. (Christine Søholm), Hansen, T.F. (Thomas F.), Herms, S. (Stefan), Hickie, I.B. (Ian), Hoffmann, P. (Per), Homuth, G. (Georg), Horn, C. (Carsten), Hottenga, J.J. (Jouke Jan), Hougaard, D.M. (David), Howard, D.M. (David M.), Ising, M. (Marcus), Jansen, R. (Rick), Jorgenson, E. (Eric), Kohane, I.S. (Isaac S.), Kraft, J. (Julia), Kretzschmar, W.W. (Warren W.), Li, Y. (Yihan), Macintyre, D.J. (Donald J), MacKinnon, D.F. (Dean F.), Maier, R.M. (Robert M.), Maier, W. (Wolfgang), Marchini, J. (Jonathan), Mbarek, H., McGrath, P. (Patrick), Medland, S.E. (Sarah), Mehta, D. (Divya), Middeldorp, C.M. (Christel), Mihailov, E. (Evelin), Milani, L. (Lili), Mondimore, F.M. (Francis M.), Montgomery, G.W. (Grant), Mullins, N. (Niamh), Nauck, M. (Matthias), Ng, B. (Bernard), Nivard, M. (Michel), Nyholt, D.R. (Dale), O'Reilly, P.F. (Paul), Oskarsson, H. (Hogni), Owen, M.J. (Michael), Painter, J.N. (Jodie N.), Pedersen, C.B. (C.), Pedersen, M.G. (Marianne Giørtz), Peterson, R.E. (Roseann E.), Pettersson, E. (Erik), Peyrot, W.J. (Wouter ), Pistis, G. (Giorgio), Posthuma, D. (Danielle), Quiroz, J.A. (Jorge A.), Qvist, P. (Per), Rice, J.P. (John), Riley, B.P. (Brien P.), Rivera, M. (Margarita), Mirza, S.S. (Saira), Schoevers, R. (Robert), Schulte, E.C. (Eva C.), Shen, L. (Li), Sigurdsson, E. (Engilbert), Sinnamon, G.C.B. (Grant C.B.), Smith, A.V. (Davey), Smith, D.J. (Daniel J.), Stefansson, H. (Hreinn), Steinberg, S. (Stacy), Strohmaier, J. (Jana), Tansey, K.E., Teismann, H. (Henning), Teumer, A. (Alexander), Thompson, W.K. (Wesley K.), Thomson, P.A. (Pippa A.), Thorgeirsson, T.E. (Thorgeir E.), Traylor, M. (Matthew), Treutlein, J. (Jens), Trubetskoy, V. (Vassily), Uitterlinden, A.G. (Andrés G.), Umbricht, D. (Daniel), van Hemert, A.M. (Albert M.), Viktorin, A. (Alexander), Visscher, P.M. (Peter M.), Wang, Y. (Yunpeng), Webb, B.T. (Bradley T.), Weinsheimer, S.M. (Shantel Marie), Wellmann, J. (Jürgen), Willemsen, G.A.H.M. (Gonneke), Witt, S.H. (Stephanie H), Wu, Y. (Yang), Xi, H.S. (Hualin S.), Yang, J. (Jian), Zhang, F. (Futao), Arolt, V. (Volker), Berger, K. (Klaus), Cichon, S. (Sven), de Geus, E.J.C. (E. J.C.), DePaulo, J.R. (J. Raymond), Domenici, E. (Enrico), Domschke, K. (Katharina), Esko, T. (Tõnu), Hayward, C. (Caroline), Heath, A.C. (Andrew), Jablensky, A. (Assen), Kloiber, S. (Stefan), Li, Q.S. (Qingqin S.), Madden, P.A. (Pamela), Martin, N.G. (Nicholas), Metspalu, A. (Andres), Mortensen, P.B. (Preben Bo), Nordentoft, M. (Merete), Nöthen, M.M. (Markus), O'donovan, M.C. (Michael), Paciga, S.A. (Sara A.), Perlis, R.H. (Roy H), Porteous, D.J. (David J.), Rietschel, M. (Marcella), Schaefer, C. (Catherine), Schulze, T.G. (Thomas G.), Zwart, J-A. (John-Anker), Völzke, H. (Henry), Werge, T.M. (Thomas), Lewis, C.M. (Cathryn), Borglum, A.D. (Anders), Glanville, K.P. (Kylie P.), Coleman, J.R.I. (Jonathan R.I.), Hanscombe, K.B. (Ken B.), Euesden, J. (Jack), Choi, S.W. (Shing Wan), Purves, K.L. (Kirstin L.), Breen, G. (Gerome), Air, T.M. (Tracy M.), Andlauer, T.F.M. (Till F.M.), Baune, B.T., Binder, E.B. (Elisabeth), Blackwood, D.H.R. (Douglas), Boomsma, D.I. (Dorret), Buttenschøn, H.N. (Henriette N.), Colodro-Conde, L. (Lucía), Dannlowski, U. (Udo), Direk, N. (Nese), Dunn, E.C. (Erin C.), Forstner, A.J. (Andreas J.), Geus, E.J.C. (Eco) de, Grabe, H.J. (Hans Jörgen), Hamilton, S.P. (Steven P), Jones, I., Jones, L. (Louisa), Knowles, J.A. (James A), Kutalik, Z. (Zoltán), Levinson, D.F. (Douglas F.), Lewis, G., Lind, P.A. (Penelope), Lucae, S. (Susanne), Magnusson, P.K. (Patrik), McGuffin, P. (Peter), McIntosh, A.M. (Andrew), Milaneschi, Y. (Yuri), Mors, O., Mostafavi, S. (Sara), Müller-Myhsok, B. (B.), Pedersen, N.L. (Nancy), Penninx, B.W.J.H. (Brenda), Potash, J.B. (James B), Preisig, M. (Martin), Ripke, S. (Stephan), Shi, J. (Jianxin), Shyn, S.I. (Stanley I), Smoller, J.W., Streit, F. (Fabian), Sullivan, P.F. (Patrick), Tiemeier, H.W. (Henning), Uher, R. (Rudolf), Van der Auwera, S. (Sandra), Weissman, M.M., Wray, N.R. (Naomi), Mattheisen, M. (Manuel), Trzaskowski, M. (Maciej), Byrne, E.M. (Enda), Abdellaoui, A. (Abdel), Adams, M.J. (Mark J.), Agerbo, E. (Esben), Bacanu, S.A. (Silviu), Bækvad-Hansen, M. (Marie), Beekman, A.T.F. (Aartjan), Bigdeli, T.B. (Tim B.), Bryois, J. (Julien), Bybjerg-Grauholm, J. (Jonas), Cai, N. (Na), Castelao, E. (Enrique), Christensen, J.H. (Jane Hvarregaard), Clarke, T.-K., Couvy-Duchesne, B. (Baptiste), Craddock, N.J. (Nick), Crawford, G.E. (Gregory E.), Davies, G. (Gail), Deary, I.J. (Ian J.), Degenhardt, F., Derks, E.M. (Eske), Dolan, C.V. (Conor), Eley, T.C. (T.), Escott-Price, V. (Valentina), Hassan Kiadeh, F.F. (Farnush Farhadi), Finucane, H.K. (Hilary K.), Foo, J.C. (Jerome C.), Frank, J. (Josef), Gaspar, H.A. (Héléna A.), Gill, M. (Michael), Goes, F.S. (Fernando S.), Gordon, S.D. (Scott D.), Grove, J. (Jakob), Hall, L.S. (Lynsey S.), Hansen, C.S. (Christine Søholm), Hansen, T.F. (Thomas F.), Herms, S. (Stefan), Hickie, I.B. (Ian), Hoffmann, P. (Per), Homuth, G. (Georg), Horn, C. (Carsten), Hottenga, J.J. (Jouke Jan), Hougaard, D.M. (David), Howard, D.M. (David M.), Ising, M. (Marcus), Jansen, R. (Rick), Jorgenson, E. (Eric), Kohane, I.S. (Isaac S.), Kraft, J. (Julia), Kretzschmar, W.W. (Warren W.), Li, Y. (Yihan), Macintyre, D.J. (Donald J), MacKinnon, D.F. (Dean F.), Maier, R.M. (Robert M.), Maier, W. (Wolfgang), Marchini, J. (Jonathan), Mbarek, H., McGrath, P. (Patrick), Medland, S.E. (Sarah), Mehta, D. (Divya), Middeldorp, C.M. (Christel), Mihailov, E. (Evelin), Milani, L. (Lili), Mondimore, F.M. (Francis M.), Montgomery, G.W. (Grant), Mullins, N. (Niamh), Nauck, M. (Matthias), Ng, B. (Bernard), Nivard, M. (Michel), Nyholt, D.R. (Dale), O'Reilly, P.F. (Paul), Oskarsson, H. (Hogni), Owen, M.J. (Michael), Painter, J.N. (Jodie N.), Pedersen, C.B. (C.), Pedersen, M.G. (Marianne Giørtz), Peterson, R.E. (Roseann E.), Pettersson, E. (Erik), Peyrot, W.J. (Wouter ), Pistis, G. (Giorgio), Posthuma, D. (Danielle), Quiroz, J.A. (Jorge A.), Qvist, P. (Per), Rice, J.P. (John), Riley, B.P. (Brien P.), Rivera, M. (Margarita), Mirza, S.S. (Saira), Schoevers, R. (Robert), Schulte, E.C. (Eva C.), Shen, L. (Li), Sigurdsson, E. (Engilbert), Sinnamon, G.C.B. (Grant C.B.), Smith, A.V. (Davey), Smith, D.J. (Daniel J.), Stefansson, H. (Hreinn), Steinberg, S. (Stacy), Strohmaier, J. (Jana), Tansey, K.E., Teismann, H. (Henning), Teumer, A. (Alexander), Thompson, W.K. (Wesley K.), Thomson, P.A. (Pippa A.), Thorgeirsson, T.E. (Thorgeir E.), Traylor, M. (Matthew), Treutlein, J. (Jens), Trubetskoy, V. (Vassily), Uitterlinden, A.G. (Andrés G.), Umbricht, D. (Daniel), van Hemert, A.M. (Albert M.), Viktorin, A. (Alexander), Visscher, P.M. (Peter M.), Wang, Y. (Yunpeng), Webb, B.T. (Bradley T.), Weinsheimer, S.M. (Shantel Marie), Wellmann, J. (Jürgen), Willemsen, G.A.H.M. (Gonneke), Witt, S.H. (Stephanie H), Wu, Y. (Yang), Xi, H.S. (Hualin S.), Yang, J. (Jian), Zhang, F. (Futao), Arolt, V. (Volker), Berger, K. (Klaus), Cichon, S. (Sven), de Geus, E.J.C. (E. J.C.), DePaulo, J.R. (J. Raymond), Domenici, E. (Enrico), Domschke, K. (Katharina), Esko, T. (Tõnu), Hayward, C. (Caroline), Heath, A.C. (Andrew), Jablensky, A. (Assen), Kloiber, S. (Stefan), Li, Q.S. (Qingqin S.), Madden, P.A. (Pamela), Martin, N.G. (Nicholas), Metspalu, A. (Andres), Mortensen, P.B. (Preben Bo), Nordentoft, M. (Merete), Nöthen, M.M. (Markus), O'donovan, M.C. (Michael), Paciga, S.A. (Sara A.), Perlis, R.H. (Roy H), Porteous, D.J. (David J.), Rietschel, M. (Marcella), Schaefer, C. (Catherine), Schulze, T.G. (Thomas G.), Zwart, J-A. (John-Anker), Völzke, H. (Henry), Werge, T.M. (Thomas), Lewis, C.M. (Cathryn), and Borglum, A.D. (Anders)

Abstract

Background: The prevalence of depression is higher in individuals with autoimmune diseases, but the mechanisms underlying the observed comorbidities are unknown. Shared genetic etiology is a plausible explanation for the overlap, and in this study we tested whether genetic variation in the major histocompatibility complex (MHC), which is associated with risk for autoimmune diseases, is also associated with risk for depression. Methods: We fine-mapped the classical MHC (chr6: 29.6–33.1 Mb), imputing 216 human leukocyte antigen (HLA) alleles and 4 complement component 4 (C4) haplotypes in studies from the Psychiatric Genomics Consortium Major Depressive Disorder Working Group and the UK Biobank. The total sample size was 45,149 depression cases and 86,698 controls. We tested for association between depression status and imputed MHC variants, applying both a region-wide significance threshold (3.9 × 10−6) and a candidate threshold (1.6 × 10−4). Results: No HLA alleles or C4 haplotypes were associated with depression at the region-wide threshold. HLA-B*08:01 was associated with modest protection for depression at the candidate threshold for testing in HLA genes in the meta-analysis (odds ratio = 0.98, 95% confidence interval = 0.97–0.99). Conclusions: We found no evidence that an increased risk for depression was conferred by HLA alleles, which play a major role in the genetic susceptibility to autoimmune diseases, or C4 haplotypes, which are strongly associated with schizophrenia. These results suggest that any HLA or C4 variants associated with depression either are rare or have very modest effect sizes.

Published
2019
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46. Integrated analysis of environmental and genetic influences on cord blood DNA methylation in new-borns

Author

Czamara, D. (Darina), Eraslan, G. (Gökçen), Page, C.M. (Christian M.), Lahti, J. (Jari), Lahti-Pulkkinen, M. (Marius), Hämäläinen, E. (Esa), Kajantie, E. (Eero), Laivuori, H. (Hannele), Villa, P.M. (Pia M.), Reynolds, R.M. (Rebecca M.), Nystad, W. (Wenche), Håberg, S.E. (Siri E), London, S.J. (Stephanie J.), O’Donnell, K.J. (Kieran J.), Garg, E. (Elika), Meaney, M.J., Entringer, S., Wadhwa, P.D. (Pathik D.), Buss, C. (Claudia), Jones, M.J. (Meaghan J.), Lin, D.T.S. (David T. S.), MacIsaac, J.L. (Julie L.), Kobor, M.S. (Michael S.), Koen, N. (Nastassja), Zar, H.J., Koenen, M.E. (Marjorie), Dalvie, S. (Shareefa), Stein, D.J. (Dan), Kondofersky, I. (Ivan), Müller, N.S. (Nikola S.), Theis, F. (Fabian), Wray, N.R. (Naomi), Ripke, S. (Stephan), Mattheisen, M. (Manuel), Trzaskowski, M. (Maciej), Byrne, E.M. (Enda), Abdellaoui, A. (Abdel), Adams, M.J. (Mark J.), Agerbo, E. (Esben), Air, T.M. (Tracy M.), Andlauer, T.F.M. (Till F. M.), Bacanu, S.A. (Silviu), Bækvad-Hansen, M. (Marie), Beekman, A.T.F. (Aartjan), Bigdeli, T.B. (Tim B.), Blackwood, D.H.R. (Douglas), Bryois, J. (Julien), Buttenschøn, H.N. (Henriette N.), Bybjerg-Grauholm, J. (Jonas), Cai, N. (Na), Castelao, E. (Enrique), Christensen, J.H. (Jane Hvarregaard), Clarke, T.-K., Coleman, J.R.I. (Jonathan R. I.), Colodro-Conde, L. (Lucía), Couvy-Duchesne, B. (Baptiste), Craddock, N.J. (Nick), Crawford, G.E. (Gregory E.), Davies, G. (Gail), Deary, I.J. (Ian), Degenhardt, F., Derks, E.M. (Eske), Direk, N. (Nese), Dolan, C.V. (Conor), Dunn, E.C. (Erin C.), Eley, T.C. (T.), Escott-Price, V. (Valentina), Kiadeh, F.F.H. (Farnush Farhadi Hassan), Finucane, H.K. (Hilary K.), Forstner, A.J. (Andreas J.), Frank, J. (Josef), Gaspar, H.A. (Héléna A.), Gill, M. (Michael), Goes, F.S. (Fernando S.), Gordon, S.D. (Scott D.), Grove, J. (Jakob), Hall, L.S. (Lynsey S.), Hansen, C.S. (Christine Søholm), Hansen, T.F. (Thomas F.), Herms, S. (Stefan), Hickie, I.B. (Ian), Hoffmann, P. (Per), Homuth, G. (Georg), Horn, C. (Carsten), Hottenga, J.J. (Jouke Jan), Hougaard, D.M. (David M.), Ising, M. (Marcus), Jansen, R. (Rick), Jorgenson, E. (Eric), Knowles, J.A. (James A), Kohane, I.S., Kraft, J. (Julia), Kretzschmar, W.W. (Warren W.), Krogh, J. (Jesper), Kutalik, Z. (Zoltán), Li, Y. (Yihan), Lind, P.A. (Penelope), Macintyre, D.J. (Donald J), MacKinnon, D.F. (Dean F.), Maier, R.M. (Robert M.), Maier, W. (Wolfgang), Marchini, J. (Jonathan), Mbarek, H., McGrath, P. (Patrick), McGuffin, P. (Peter), Medland, S.E. (Sarah), Mehta, D. (Divya), Middeldorp, C.M. (Christel), Mihailov, E. (Evelin), Milaneschi, Y. (Yuri), Milani, L. (Lili), Mondimore, F.M. (Francis M.), Montgomery, G.W. (Grant), Mostafavi, S. (Sara), Mullins, N. (Niamh), Nauck, M. (Matthias), Ng, B. (Bernard), Nivard, M. (Michel), Nyholt, D.R. (Dale), O’Reilly, P.F. (Paul F.), Oskarsson, H. (Hogni), Owen, M.J. (Michael J.), Painter, J.N. (Jodie N.), Pedersen, C.B. (C.), Pedersen, M.G. (Marianne Giørtz), Peterson, R.E. (Roseann E.), Pettersson, E. (Erik), Peyrot, W.J. (Wouter ), Pistis, G. (Giorgio), Posthuma, D. (Danielle), Quiroz, J.A. (Jorge A.), Qvist, P. (Per), Rice, J.P. (John), Riley, B.P. (Brien P.), Rivera, M. (Margarita), Mirza, S.S. (Saira), Schoevers, R. (Robert), Schulte, E.C. (Eva C.), Shen, L. (Ling), Shi, J. (Jianxin), Shyn, S.I. (Stanley I), Sigurdsson, E. (Engilbert), Sinnamon, G.C.B. (Grant C. B.), Smith, A.V. (Davey), Smith, D.J. (Daniel J.), Stefansson, H. (Hreinn), Steinberg, S. (Stacy), Streit, F. (Fabian), Strohmaier, J. (Jana), Tansey, K.E., Teismann, H. (Henning), Teumer, A. (Alexander), Thompson, W.K. (Wesley K.), Thomson, P.A. (Pippa A.), Thorgeirsson, T.E. (Thorgeir E.), Traylor, M. (Matthew), Treutlein, J. (Jens), Trubetskoy, V. (Vassily), Uitterlinden, A.G. (André), Umbricht, D. (Daniel), Van der Auwera, S. (Sandra), van Hemert, A.M. (Albert M.), Viktorin, A. (Alexander), Visscher, P.M. (Peter M.), Wang, Y. (Yunpeng), Webb, B.T. (Bradley T.), Weinsheimer, S.M. (Shantel Marie), Wellmann, J. (Jürgen), Willemsen, G.A.H.M. (Gonneke), Witt, S.H. (Stephanie H), Wu, Y. (Yang), Xi, H.S. (Hualin S.), Yang, J. (Jian), Zhang, F. (Futao), Arolt, V. (Volker), Baune, B.T., Berger, K. (Klaus), Boomsma, D.I. (Dorret), Cichon, S. (Sven), Dannlowski, U. (Udo), Geus, E.J.C. (Eco) de, DePaulo, J.R. (J. Raymond), Domenici, E. (Enrico), Domschke, K. (Katharina), Esko, T. (Tõnu), Grabe, H.J. (Hans Jörgen), Hamilton, S.P. (Steven P), Hayward, C. (Caroline), Heath, A.C. (Andrew), Jablensky, A. (Assen), Kloiber, S. (Stefan), Lewis, G., Li, Q.S. (Qingqin S.), Lucae, S. (Susanne), Madden, P.A. (Pamela), Magnusson, P.K. (Patrik K.), Martin, N.G. (Nicholas), McIntosh, A.M. (Andrew M.), Metspalu, A. (Andres), Mors, O. (Ole), Mortensen, P.B. (Preben Bo), Müller-Myhsok, B. (B.), Nordentoft, M. (Merete), Nöthen, M.M. (Markus), O’Donovan, M.C. (Michael C.), Paciga, S.A. (Sara A.), Pedersen, N.L. (Nancy), Penninx, B.W.J.H. (Brenda), Perlis, R.H. (Roy H), Porteous, D.J. (David J.), Potash, J.B. (James B), Preisig, M. (Martin), Rietschel, M. (Marcella), Schaefer, C. (Catherine), Schulze, T.G. (Thomas G.), Smoller, J.W., Stefansson, K. (Kari), Tiemeier, H.W. (Henning), Uher, R. (Rudolf), Völzke, H. (Henry), Weissman, M.M., Werge, T. (Thomas), Lewis, C.M. (Cathryn), Levinson, D.F. (Douglas F.), Breen, G. (Gerome), Borglum, A.D. (Anders), Sullivan, P.F. (Patrick F.), Räikkönen, K. (Katri), Binder, E.B. (Elisabeth), Czamara, D. (Darina), Eraslan, G. (Gökçen), Page, C.M. (Christian M.), Lahti, J. (Jari), Lahti-Pulkkinen, M. (Marius), Hämäläinen, E. (Esa), Kajantie, E. (Eero), Laivuori, H. (Hannele), Villa, P.M. (Pia M.), Reynolds, R.M. (Rebecca M.), Nystad, W. (Wenche), Håberg, S.E. (Siri E), London, S.J. (Stephanie J.), O’Donnell, K.J. (Kieran J.), Garg, E. (Elika), Meaney, M.J., Entringer, S., Wadhwa, P.D. (Pathik D.), Buss, C. (Claudia), Jones, M.J. (Meaghan J.), Lin, D.T.S. (David T. S.), MacIsaac, J.L. (Julie L.), Kobor, M.S. (Michael S.), Koen, N. (Nastassja), Zar, H.J., Koenen, M.E. (Marjorie), Dalvie, S. (Shareefa), Stein, D.J. (Dan), Kondofersky, I. (Ivan), Müller, N.S. (Nikola S.), Theis, F. (Fabian), Wray, N.R. (Naomi), Ripke, S. (Stephan), Mattheisen, M. (Manuel), Trzaskowski, M. (Maciej), Byrne, E.M. (Enda), Abdellaoui, A. (Abdel), Adams, M.J. (Mark J.), Agerbo, E. (Esben), Air, T.M. (Tracy M.), Andlauer, T.F.M. (Till F. M.), Bacanu, S.A. (Silviu), Bækvad-Hansen, M. (Marie), Beekman, A.T.F. (Aartjan), Bigdeli, T.B. (Tim B.), Blackwood, D.H.R. (Douglas), Bryois, J. (Julien), Buttenschøn, H.N. (Henriette N.), Bybjerg-Grauholm, J. (Jonas), Cai, N. (Na), Castelao, E. (Enrique), Christensen, J.H. (Jane Hvarregaard), Clarke, T.-K., Coleman, J.R.I. (Jonathan R. I.), Colodro-Conde, L. (Lucía), Couvy-Duchesne, B. (Baptiste), Craddock, N.J. (Nick), Crawford, G.E. (Gregory E.), Davies, G. (Gail), Deary, I.J. (Ian), Degenhardt, F., Derks, E.M. (Eske), Direk, N. (Nese), Dolan, C.V. (Conor), Dunn, E.C. (Erin C.), Eley, T.C. (T.), Escott-Price, V. (Valentina), Kiadeh, F.F.H. (Farnush Farhadi Hassan), Finucane, H.K. (Hilary K.), Forstner, A.J. (Andreas J.), Frank, J. (Josef), Gaspar, H.A. (Héléna A.), Gill, M. (Michael), Goes, F.S. (Fernando S.), Gordon, S.D. (Scott D.), Grove, J. (Jakob), Hall, L.S. (Lynsey S.), Hansen, C.S. (Christine Søholm), Hansen, T.F. (Thomas F.), Herms, S. (Stefan), Hickie, I.B. (Ian), Hoffmann, P. (Per), Homuth, G. (Georg), Horn, C. (Carsten), Hottenga, J.J. (Jouke Jan), Hougaard, D.M. (David M.), Ising, M. (Marcus), Jansen, R. (Rick), Jorgenson, E. (Eric), Knowles, J.A. (James A), Kohane, I.S., Kraft, J. (Julia), Kretzschmar, W.W. (Warren W.), Krogh, J. (Jesper), Kutalik, Z. (Zoltán), Li, Y. (Yihan), Lind, P.A. (Penelope), Macintyre, D.J. (Donald J), MacKinnon, D.F. (Dean F.), Maier, R.M. (Robert M.), Maier, W. (Wolfgang), Marchini, J. (Jonathan), Mbarek, H., McGrath, P. (Patrick), McGuffin, P. (Peter), Medland, S.E. (Sarah), Mehta, D. (Divya), Middeldorp, C.M. (Christel), Mihailov, E. (Evelin), Milaneschi, Y. (Yuri), Milani, L. (Lili), Mondimore, F.M. (Francis M.), Montgomery, G.W. (Grant), Mostafavi, S. (Sara), Mullins, N. (Niamh), Nauck, M. (Matthias), Ng, B. (Bernard), Nivard, M. (Michel), Nyholt, D.R. (Dale), O’Reilly, P.F. (Paul F.), Oskarsson, H. (Hogni), Owen, M.J. (Michael J.), Painter, J.N. (Jodie N.), Pedersen, C.B. (C.), Pedersen, M.G. (Marianne Giørtz), Peterson, R.E. (Roseann E.), Pettersson, E. (Erik), Peyrot, W.J. (Wouter ), Pistis, G. (Giorgio), Posthuma, D. (Danielle), Quiroz, J.A. (Jorge A.), Qvist, P. (Per), Rice, J.P. (John), Riley, B.P. (Brien P.), Rivera, M. (Margarita), Mirza, S.S. (Saira), Schoevers, R. (Robert), Schulte, E.C. (Eva C.), Shen, L. (Ling), Shi, J. (Jianxin), Shyn, S.I. (Stanley I), Sigurdsson, E. (Engilbert), Sinnamon, G.C.B. (Grant C. B.), Smith, A.V. (Davey), Smith, D.J. (Daniel J.), Stefansson, H. (Hreinn), Steinberg, S. (Stacy), Streit, F. (Fabian), Strohmaier, J. (Jana), Tansey, K.E., Teismann, H. (Henning), Teumer, A. (Alexander), Thompson, W.K. (Wesley K.), Thomson, P.A. (Pippa A.), Thorgeirsson, T.E. (Thorgeir E.), Traylor, M. (Matthew), Treutlein, J. (Jens), Trubetskoy, V. (Vassily), Uitterlinden, A.G. (André), Umbricht, D. (Daniel), Van der Auwera, S. (Sandra), van Hemert, A.M. (Albert M.), Viktorin, A. (Alexander), Visscher, P.M. (Peter M.), Wang, Y. (Yunpeng), Webb, B.T. (Bradley T.), Weinsheimer, S.M. (Shantel Marie), Wellmann, J. (Jürgen), Willemsen, G.A.H.M. (Gonneke), Witt, S.H. (Stephanie H), Wu, Y. (Yang), Xi, H.S. (Hualin S.), Yang, J. (Jian), Zhang, F. (Futao), Arolt, V. (Volker), Baune, B.T., Berger, K. (Klaus), Boomsma, D.I. (Dorret), Cichon, S. (Sven), Dannlowski, U. (Udo), Geus, E.J.C. (Eco) de, DePaulo, J.R. (J. Raymond), Domenici, E. (Enrico), Domschke, K. (Katharina), Esko, T. (Tõnu), Grabe, H.J. (Hans Jörgen), Hamilton, S.P. (Steven P), Hayward, C. (Caroline), Heath, A.C. (Andrew), Jablensky, A. (Assen), Kloiber, S. (Stefan), Lewis, G., Li, Q.S. (Qingqin S.), Lucae, S. (Susanne), Madden, P.A. (Pamela), Magnusson, P.K. (Patrik K.), Martin, N.G. (Nicholas), McIntosh, A.M. (Andrew M.), Metspalu, A. (Andres), Mors, O. (Ole), Mortensen, P.B. (Preben Bo), Müller-Myhsok, B. (B.), Nordentoft, M. (Merete), Nöthen, M.M. (Markus), O’Donovan, M.C. (Michael C.), Paciga, S.A. (Sara A.), Pedersen, N.L. (Nancy), Penninx, B.W.J.H. (Brenda), Perlis, R.H. (Roy H), Porteous, D.J. (David J.), Potash, J.B. (James B), Preisig, M. (Martin), Rietschel, M. (Marcella), Schaefer, C. (Catherine), Schulze, T.G. (Thomas G.), Smoller, J.W., Stefansson, K. (Kari), Tiemeier, H.W. (Henning), Uher, R. (Rudolf), Völzke, H. (Henry), Weissman, M.M., Werge, T. (Thomas), Lewis, C.M. (Cathryn), Levinson, D.F. (Douglas F.), Breen, G. (Gerome), Borglum, A.D. (Anders), Sullivan, P.F. (Patrick F.), Räikkönen, K. (Katri), and Binder, E.B. (Elisabeth)

Abstract

Epigenetic processes, including DNA methylation (DNAm), are among the mechanisms allowing integration of genetic and environmental factors to shape cellular function. While many studies have investigated either environmental or genetic contributions to DNAm, few have assessed their integrated effects. Here we examine the relative contributions of prenatal environmental factors and genotype on DNA methylation in neonatal blood at variably methylated regions (VMRs) in 4 independent cohorts (overall n = 2365). We use Akaike’s information criterion to test which factors best explain variability of methylation in the cohort-specific VMRs: several prenatal environmental factors (E), genotypes in cis (G), or their additive (G + E) or interaction (GxE) effects. Genetic and environmental factors in combination best explain DNAm at the majority of VMRs. The CpGs best explained by either G, G + E or GxE are functionally distinct. The enrichment of genetic variants from GxE models in GWAS for complex disorders supports their importance for disease risk.

Published
2019
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47. Evidence for increased genetic risk load for major depression in patients assigned to electroconvulsive therapy

Author

Foo, JC, Streit, F, Frank, J, Witt, SH, Treutlein, J, Baune, BT, Moebus, S, Joeckel, K-H, Forstner, AJ, Noethen, MM, Rietschel, M, Sartorius, A, Kranaster, L, Wray, NR, Ripke, S, Mattheisen, M, Trzaskowski, M, Byrne, EM, Abdellaoui, A, Adams, MJ, Agerbo, E, Air, TM, Andlauer, TFM, Bacanu, S-A, Baekvad-Hansen, M, Beekman, ATF, Bigdeli, TB, Binder, EB, Blackwood, DHR, Bryois, J, Buttenschon, HN, Bybjerg-Grauholm, J, Cai, N, Castelao, E, Christensen, JH, Clarke, T-K, Coleman, JRI, Colodro-Conde, L, Couvy-Duchesne, B, Craddock, N, Crawford, GE, Davies, G, Deary, IJ, Degenhardt, F, Derks, EM, Direk, N, Dolan, CV, Dunn, EC, Eley, TC, Escott-Price, V, Kiadeh, FFH, Finucane, HK, Gaspar, HA, Gill, M, Goes, FS, Gordon, SD, Grove, J, Hall, LS, Hansen, CS, Hansen, TF, Herms, S, Hickie, IB, Hoffmann, P, Homuth, G, Horn, C, Hottenga, J-J, Hougaard, DM, Ising, M, Jansen, R, Jones, I, Jones, LA, Jorgenson, E, Knowles, JA, Kohane, IS, Kraft, J, Kretzschmar, WW, Krogh, J, Kutalik, Z, Li, Y, Lind, PA, MacIntyre, DJ, MacKinnon, DF, Maier, RM, Maier, W, Marchini, J, Mbarek, H, McGrath, P, McGuffin, P, Medland, SE, Mehta, D, Middeldorp, CM, Mihailov, E, Milaneschi, Y, Milani, L, Mondimore, FM, Montgomery, GW, Mostafavi, S, Mullins, N, Nauck, M, Ng, B, Nivard, MG, Nyholt, DR, O'Reilly, PF, Oskarsson, H, Owen, MJ, Painter, JN, Pedersen, CB, Pedersen, MG, Peterson, RE, Pettersson, E, Peyrot, WJ, Pistis, G, Posthuma, D, Quiroz, JA, Qvist, P, Rice, JP, Riley, BP, Rivera, M, Mirza, SS, Schoevers, R, Schulte, EC, Shen, L, Shi, J, Shyn, SI, Sigurdsson, E, Sinnamon, GCB, Smit, JH, Smith, DJ, Stefansson, H, Steinberg, S, Strohmaier, J, Tansey, KE, Teismann, H, Teumer, A, Thompson, W, Thomson, PA, Thorgeirsson, TE, Traylor, M, Trubetskoy, V, Uitterlinden, AG, Umbricht, D, Van der Auwera, S, van Hemert, AM, Viktorin, A, Visscher, PM, Wang, Y, Webb, BT, Weinsheimer, SM, Wellmann, J, Willemsen, G, Wu, Y, Xi, HS, Yang, J, Zhang, F, Arolt, V, Berger, K, Boomsma, DI, Cichon, S, Dannlowski, U, de Geus, EJC, DePaulo, JR, Domenici, E, Domschke, K, Esko, T, Grabe, HJ, Hamilton, SP, Hayward, C, Heath, AC, Kendler, KS, Kloiber, S, Lewis, G, Li, QS, Lucae, S, Madden, PAF, Magnusson, PK, Martin, NG, McIntosh, AM, Metspalu, A, Mors, O, Mortensen, PB, Mueller-Myhsok, B, Nordentoft, M, O'Donovan, MC, Paciga, SA, Pedersen, NL, Penninx, BWJH, Perlis, RH, Porteous, DJ, Potash, JB, Preisig, M, Schaefer, C, Schulze, TG, Smoller, JW, Stefansson, K, Tiemeier, H, Uher, R, Voelzke, H, Weissman, MM, Werge, T, Lewis, CM, Levinson, DF, Breen, G, Borglum, AD, Sullivan, PF, Foo, JC, Streit, F, Frank, J, Witt, SH, Treutlein, J, Baune, BT, Moebus, S, Joeckel, K-H, Forstner, AJ, Noethen, MM, Rietschel, M, Sartorius, A, Kranaster, L, Wray, NR, Ripke, S, Mattheisen, M, Trzaskowski, M, Byrne, EM, Abdellaoui, A, Adams, MJ, Agerbo, E, Air, TM, Andlauer, TFM, Bacanu, S-A, Baekvad-Hansen, M, Beekman, ATF, Bigdeli, TB, Binder, EB, Blackwood, DHR, Bryois, J, Buttenschon, HN, Bybjerg-Grauholm, J, Cai, N, Castelao, E, Christensen, JH, Clarke, T-K, Coleman, JRI, Colodro-Conde, L, Couvy-Duchesne, B, Craddock, N, Crawford, GE, Davies, G, Deary, IJ, Degenhardt, F, Derks, EM, Direk, N, Dolan, CV, Dunn, EC, Eley, TC, Escott-Price, V, Kiadeh, FFH, Finucane, HK, Gaspar, HA, Gill, M, Goes, FS, Gordon, SD, Grove, J, Hall, LS, Hansen, CS, Hansen, TF, Herms, S, Hickie, IB, Hoffmann, P, Homuth, G, Horn, C, Hottenga, J-J, Hougaard, DM, Ising, M, Jansen, R, Jones, I, Jones, LA, Jorgenson, E, Knowles, JA, Kohane, IS, Kraft, J, Kretzschmar, WW, Krogh, J, Kutalik, Z, Li, Y, Lind, PA, MacIntyre, DJ, MacKinnon, DF, Maier, RM, Maier, W, Marchini, J, Mbarek, H, McGrath, P, McGuffin, P, Medland, SE, Mehta, D, Middeldorp, CM, Mihailov, E, Milaneschi, Y, Milani, L, Mondimore, FM, Montgomery, GW, Mostafavi, S, Mullins, N, Nauck, M, Ng, B, Nivard, MG, Nyholt, DR, O'Reilly, PF, Oskarsson, H, Owen, MJ, Painter, JN, Pedersen, CB, Pedersen, MG, Peterson, RE, Pettersson, E, Peyrot, WJ, Pistis, G, Posthuma, D, Quiroz, JA, Qvist, P, Rice, JP, Riley, BP, Rivera, M, Mirza, SS, Schoevers, R, Schulte, EC, Shen, L, Shi, J, Shyn, SI, Sigurdsson, E, Sinnamon, GCB, Smit, JH, Smith, DJ, Stefansson, H, Steinberg, S, Strohmaier, J, Tansey, KE, Teismann, H, Teumer, A, Thompson, W, Thomson, PA, Thorgeirsson, TE, Traylor, M, Trubetskoy, V, Uitterlinden, AG, Umbricht, D, Van der Auwera, S, van Hemert, AM, Viktorin, A, Visscher, PM, Wang, Y, Webb, BT, Weinsheimer, SM, Wellmann, J, Willemsen, G, Wu, Y, Xi, HS, Yang, J, Zhang, F, Arolt, V, Berger, K, Boomsma, DI, Cichon, S, Dannlowski, U, de Geus, EJC, DePaulo, JR, Domenici, E, Domschke, K, Esko, T, Grabe, HJ, Hamilton, SP, Hayward, C, Heath, AC, Kendler, KS, Kloiber, S, Lewis, G, Li, QS, Lucae, S, Madden, PAF, Magnusson, PK, Martin, NG, McIntosh, AM, Metspalu, A, Mors, O, Mortensen, PB, Mueller-Myhsok, B, Nordentoft, M, O'Donovan, MC, Paciga, SA, Pedersen, NL, Penninx, BWJH, Perlis, RH, Porteous, DJ, Potash, JB, Preisig, M, Schaefer, C, Schulze, TG, Smoller, JW, Stefansson, K, Tiemeier, H, Uher, R, Voelzke, H, Weissman, MM, Werge, T, Lewis, CM, Levinson, DF, Breen, G, Borglum, AD, and Sullivan, PF

Abstract

Electroconvulsive therapy (ECT) is the treatment of choice for severe and treatment-resistant depression; disorder severity and unfavorable treatment outcomes are shown to be influenced by an increased genetic burden for major depression (MD). Here, we tested whether ECT assignment and response/nonresponse are associated with an increased genetic burden for major depression (MD) using polygenic risk score (PRS), which summarize the contribution of disease-related common risk variants. Fifty-one psychiatric inpatients suffering from a major depressive episode underwent ECT. MD-PRS were calculated for these inpatients and a separate population-based sample (n = 3,547 healthy; n = 426 self-reported depression) based on summary statistics from the Psychiatric Genomics Consortium MDD-working group (Cases: n = 59,851; Controls: n = 113,154). MD-PRS explained a significant proportion of disease status between ECT patients and healthy controls (p = .022, R2 = 1.173%); patients showed higher MD-PRS. MD-PRS in population-based depression self-reporters were intermediate between ECT patients and controls (n.s.). Significant associations between MD-PRS and ECT response (50% reduction in Hamilton depression rating scale scores) were not observed. Our findings indicate that ECT cohorts show an increased genetic burden for MD and are consistent with the hypothesis that treatment-resistant MD patients represent a subgroup with an increased genetic risk for MD. Larger samples are needed to better substantiate these findings.

Published
2019

48. Genome-wide by environment interaction studies of depressive symptoms and psychosocial stress in UK Biobank and Generation Scotland

Author

Arnau-Soler, A, Macdonald-Dunlop, E, Adams, MJ, Clarke, T-K, MacIntyre, DJ, Milburn, K, Navrady, L, Hayward, C, McIntosh, AM, Thomson, PA, Wray, NR, Ripke, S, Mattheisen, M, Trzaskowski, M, Byrne, EM, Abdellaoui, A, Agerbo, E, Air, TM, Andlauer, TFM, Bacanu, S-A, Baekvad-Hansen, M, Beekman, ATF, Bigdeli, TB, Binder, EB, Blackwood, DHR, Bryois, J, Buttenscon, HN, Bybjerg-Grauholm, J, Cai, N, Castelao, E, Christensen, JH, Coleman, JR, Colodro-Conde, L, Couvy-Duchesne, B, Craddock, N, Rawford, GEC, Davies, G, Deary, IJ, Degenhardt, F, Derks, EM, Direk, N, Dolan, C, Dunn, EC, Eley, TC, Escott-Price, V, Kiadeh, FFH, Finucane, HK, Foo, JC, Forstner, AJ, Frank, J, Gaspar, HA, Gill, M, Goes, FS, Gordon, SD, Grove, J, Hall, LS, Hansen, CS, Hansen, TF, Herms, S, Hickie, IB, Hoffmann, P, Homuth, G, Horn, C, Hottenga, J-J, Hougaard, DM, Ising, M, Jansen, R, Jones, I, Jones, LA, Jorgenson, E, Knowles, JA, Kohane, IS, Kraft, J, Kretzschmar, WW, Krogh, J, Kutalik, Z, Li, Y, Lind, PA, Macintyre, DJ, MacKinnon, DF, Maier, RM, Maier, W, Marchini, J, Mbarek, H, McGrath, P, McGuffin, P, Medland, SE, Mehta, D, Middeldorp, CM, Mihailov, E, Milaneschi, Y, Milani, L, Mondimore, FM, Montgomery, GW, Mostafavi, S, Mullins, N, Nauck, M, Ng, B, Nivard, MG, Nyholt, DR, O'Reilly, PF, Oskarsson, H, Owen, MJ, Painter, JN, Pedersen, CB, Pedersen, MG, Peterson, RE, Pettersson, E, Peyrot, WJ, Pistis, G, Posthuma, D, Quiroz, JA, Qvist, P, Rice, JP, Riley, BP, Rivera, M, Mirza, SS, Schoevers, R, Schulte, EC, Shen, L, Shi, J, Shyn, S, Sigurdsson, E, Sinnamon, GCB, Smit, JH, Smith, DJ, Stefansson, H, Steinberg, S, Streit, F, Strohmaier, J, Tansey, KE, Teismann, H, Teumer, A, Thompson, W, Thorgeirsson, TE, Traylor, M, Treutlein, J, Trubetskoy, V, Uitterlinden, AG, Umbricht, D, Van der Auwera, S, van Hemert, AM, Viktorin, A, Visscher, PM, Wang, Y, Webb, BT, Weinsheimer, SM, Wellmann, J, Willemsen, G, Witt, SH, Wu, Y, Xi, HS, Yang, J, Zhang, F, Arolt, V, Baune, BT, Berger, K, Boomsma, D, Cichon, S, Dannlowski, U, de Geus, EJC, DePaulo, JR, Domenici, E, Domschke, K, Esko, T, Grabe, HJ, Hamilton, SP, Heath, AC, Kendler, KS, Kloiber, S, Lewis, G, Li, QS, Lucae, S, Madden, PAF, Magnusson, PK, Martin, NG, Metspalu, A, Mors, O, Mortensen, PB, Mueller-Myhsok, B, Nordentoft, M, Noethen, MM, O'Donovan, MC, Paciga, SA, Pedersen, NL, Penninx, BWJH, Perlis, RH, Porteous, DJ, Potash, JB, Preisig, M, Rietschel, M, Schaefer, C, Schulze, TG, Smoller, JW, Stefansson, K, Tiemeier, H, Uher, R, Voelzke, H, Weissman, MM, Werge, T, Lewis, CM, Levinson, DF, Breen, G, Borglum, ASD, Sullivan, PF, Arnau-Soler, A, Macdonald-Dunlop, E, Adams, MJ, Clarke, T-K, MacIntyre, DJ, Milburn, K, Navrady, L, Hayward, C, McIntosh, AM, Thomson, PA, Wray, NR, Ripke, S, Mattheisen, M, Trzaskowski, M, Byrne, EM, Abdellaoui, A, Agerbo, E, Air, TM, Andlauer, TFM, Bacanu, S-A, Baekvad-Hansen, M, Beekman, ATF, Bigdeli, TB, Binder, EB, Blackwood, DHR, Bryois, J, Buttenscon, HN, Bybjerg-Grauholm, J, Cai, N, Castelao, E, Christensen, JH, Coleman, JR, Colodro-Conde, L, Couvy-Duchesne, B, Craddock, N, Rawford, GEC, Davies, G, Deary, IJ, Degenhardt, F, Derks, EM, Direk, N, Dolan, C, Dunn, EC, Eley, TC, Escott-Price, V, Kiadeh, FFH, Finucane, HK, Foo, JC, Forstner, AJ, Frank, J, Gaspar, HA, Gill, M, Goes, FS, Gordon, SD, Grove, J, Hall, LS, Hansen, CS, Hansen, TF, Herms, S, Hickie, IB, Hoffmann, P, Homuth, G, Horn, C, Hottenga, J-J, Hougaard, DM, Ising, M, Jansen, R, Jones, I, Jones, LA, Jorgenson, E, Knowles, JA, Kohane, IS, Kraft, J, Kretzschmar, WW, Krogh, J, Kutalik, Z, Li, Y, Lind, PA, Macintyre, DJ, MacKinnon, DF, Maier, RM, Maier, W, Marchini, J, Mbarek, H, McGrath, P, McGuffin, P, Medland, SE, Mehta, D, Middeldorp, CM, Mihailov, E, Milaneschi, Y, Milani, L, Mondimore, FM, Montgomery, GW, Mostafavi, S, Mullins, N, Nauck, M, Ng, B, Nivard, MG, Nyholt, DR, O'Reilly, PF, Oskarsson, H, Owen, MJ, Painter, JN, Pedersen, CB, Pedersen, MG, Peterson, RE, Pettersson, E, Peyrot, WJ, Pistis, G, Posthuma, D, Quiroz, JA, Qvist, P, Rice, JP, Riley, BP, Rivera, M, Mirza, SS, Schoevers, R, Schulte, EC, Shen, L, Shi, J, Shyn, S, Sigurdsson, E, Sinnamon, GCB, Smit, JH, Smith, DJ, Stefansson, H, Steinberg, S, Streit, F, Strohmaier, J, Tansey, KE, Teismann, H, Teumer, A, Thompson, W, Thorgeirsson, TE, Traylor, M, Treutlein, J, Trubetskoy, V, Uitterlinden, AG, Umbricht, D, Van der Auwera, S, van Hemert, AM, Viktorin, A, Visscher, PM, Wang, Y, Webb, BT, Weinsheimer, SM, Wellmann, J, Willemsen, G, Witt, SH, Wu, Y, Xi, HS, Yang, J, Zhang, F, Arolt, V, Baune, BT, Berger, K, Boomsma, D, Cichon, S, Dannlowski, U, de Geus, EJC, DePaulo, JR, Domenici, E, Domschke, K, Esko, T, Grabe, HJ, Hamilton, SP, Heath, AC, Kendler, KS, Kloiber, S, Lewis, G, Li, QS, Lucae, S, Madden, PAF, Magnusson, PK, Martin, NG, Metspalu, A, Mors, O, Mortensen, PB, Mueller-Myhsok, B, Nordentoft, M, Noethen, MM, O'Donovan, MC, Paciga, SA, Pedersen, NL, Penninx, BWJH, Perlis, RH, Porteous, DJ, Potash, JB, Preisig, M, Rietschel, M, Schaefer, C, Schulze, TG, Smoller, JW, Stefansson, K, Tiemeier, H, Uher, R, Voelzke, H, Weissman, MM, Werge, T, Lewis, CM, Levinson, DF, Breen, G, Borglum, ASD, and Sullivan, PF

Abstract

Stress is associated with poorer physical and mental health. To improve our understanding of this link, we performed genome-wide association studies (GWAS) of depressive symptoms and genome-wide by environment interaction studies (GWEIS) of depressive symptoms and stressful life events (SLE) in two UK population-based cohorts (Generation Scotland and UK Biobank). No SNP was individually significant in either GWAS, but gene-based tests identified six genes associated with depressive symptoms in UK Biobank (DCC, ACSS3, DRD2, STAG1, FOXP2 and KYNU; p < 2.77 × 10-6). Two SNPs with genome-wide significant GxE effects were identified by GWEIS in Generation Scotland: rs12789145 (53-kb downstream PIWIL4; p = 4.95 × 10-9; total SLE) and rs17070072 (intronic to ZCCHC2; p = 1.46 × 10-8; dependent SLE). A third locus upstream CYLC2 (rs12000047 and rs12005200, p < 2.00 × 10-8; dependent SLE) when the joint effect of the SNP main and GxE effects was considered. GWEIS gene-based tests identified: MTNR1B with GxE effect with dependent SLE in Generation Scotland; and PHF2 with the joint effect in UK Biobank (p < 2.77 × 10-6). Polygenic risk scores (PRSs) analyses incorporating GxE effects improved the prediction of depressive symptom scores, when using weights derived from either the UK Biobank GWAS of depressive symptoms (p = 0.01) or the PGC GWAS of major depressive disorder (p = 5.91 × 10-3). Using an independent sample, PRS derived using GWEIS GxE effects provided evidence of shared aetiologies between depressive symptoms and schizotypal personality, heart disease and COPD. Further such studies are required and may result in improved treatments for depression and other stress-related conditions.

Published
2019

49. Integrated analysis of environmental and genetic influences on cord blood DNA methylation in new-borns

Author

Czamara, D, Eraslan, G, Page, CM, Lahti, J, Lahti-Pulkkinen, M, Hamalainen, E, Kajantie, E, Laivuori, H, Villa, PM, Reynolds, RM, Nystad, W, Haberg, SE, London, SJ, O'Donnell, KJ, Garg, E, Meaney, MJ, Entringer, S, Wadhwa, PD, Buss, C, Jones, MJ, Lin, DTS, MacIsaac, JL, Kobor, MS, Koen, N, Zar, HJ, Koenen, KC, Dalvie, S, Stein, DJ, Kondofersky, I, Mueller, NS, Theis, FJ, Raikkonen, K, Binder, EB, Wray, NR, Ripke, S, Mattheisen, M, Trzaskowski, M, Byrne, EM, Abdellaoui, A, Adams, MJ, Agerbo, E, Air, TM, Andlauer, TFM, Bacanu, S-A, Baekvad-Hansen, M, Beekman, ATF, Bigdeli, TB, Blackwood, DHR, Bryois, J, Buttenschon, HN, Bybjerg-Grauholm, J, Cai, N, Castelao, E, Christensen, JH, Clarke, T-K, Coleman, JR, Colodro-Conde, L, Couvy-Duchesne, B, Craddock, N, Crawford, GE, Davies, G, Deary, IJ, Degenhardt, F, Derks, EM, Direk, N, Dolan, C, Dunn, EC, Eley, TC, Escott-Price, V, Kiadeh, FFH, Finucane, HK, Forstner, AJ, Frank, J, Gaspar, HA, Gill, M, Goes, FS, Gordon, SD, Grove, J, Hall, LS, Hansen, CS, Hansen, TF, Herms, S, Hickie, IB, Hoffmann, P, Homuth, G, Horn, C, Hottenga, J-J, Hougaard, DM, Ising, M, Jansen, R, Jorgenson, E, Knowles, JA, Kohane, IS, Kraft, J, Kretzschmar, WW, Krogh, J, Kutalik, Z, Li, Y, Lind, PA, MacIntyre, DJ, MacKinnon, DF, Maier, RM, Maier, W, Marchini, J, Mbarek, H, McGrath, P, McGuffin, P, Medland, SE, Mehta, D, Middeldorp, CM, Mihailov, E, Milaneschi, Y, Milani, L, Mondimore, FM, Montgomery, GW, Mostafavi, S, Mullins, N, Nauck, M, Ng, B, Nivard, MG, Nyholt, DR, O'Reilly, PF, Oskarsson, H, Owen, MJ, Painter, JN, Pedersen, CB, Pedersen, MG, Peterson, RE, Pettersson, E, Peyrot, WJ, Pistis, G, Posthuma, D, Quiroz, JA, Qvist, P, Rice, JP, Riley, BP, Rivera, M, Mirza, SS, Schoevers, R, Schulte, EC, Shen, L, Shi, J, Shyn, S, Sigurdsson, E, Sinnamon, GCB, Smit, JH, Smith, DJ, Stefansson, H, Steinberg, S, Streit, F, Strohmaier, J, Tansey, KE, Teismann, H, Teumer, A, Thompson, W, Thomson, PA, Thorgeirsson, TE, Traylor, M, Treutlein, J, Trubetskoy, V, Uitterlinden, AG, Umbricht, D, Van der Auwera, S, van Hemert, AM, Viktorin, A, Visscher, PM, Wang, Y, Webb, BT, Weinsheimer, SM, Wellmann, J, Willemsen, G, Witt, SH, Wu, Y, Xi, HS, Yang, J, Zhang, F, Arolt, V, Baune, BT, Berger, K, Boomsma, D, Cichon, S, Dannlowski, U, de Geus, EJC, DePaulo, JR, Domenici, E, Domschke, K, Esko, T, Grabe, HJ, Hamilton, SP, Hayward, C, Heath, AC, Kendler, KS, Kloiber, S, Lewis, G, Li, QS, Lucae, S, Madden, PAF, Magnusson, PK, Martin, NG, McIntosh, AM, Metspalu, A, Mors, O, Mortensen, PB, Mueller-Myhsok, B, Nordentoft, M, Noethen, MM, O'Donovan, MC, Paciga, SA, Pedersen, NL, Penninx, BWJH, Perlis, RH, Porteous, DJ, Potash, JB, Preisig, M, Rietschel, M, Schaefer, C, Schulze, TG, Smoller, JW, Stefansson, K, Tiemeier, H, Uher, R, Voelzke, H, Weissman, MM, Werge, T, Lewis, CM, Levinson, DF, Breen, G, Borglum, AD, Sullivan, PF, Czamara, D, Eraslan, G, Page, CM, Lahti, J, Lahti-Pulkkinen, M, Hamalainen, E, Kajantie, E, Laivuori, H, Villa, PM, Reynolds, RM, Nystad, W, Haberg, SE, London, SJ, O'Donnell, KJ, Garg, E, Meaney, MJ, Entringer, S, Wadhwa, PD, Buss, C, Jones, MJ, Lin, DTS, MacIsaac, JL, Kobor, MS, Koen, N, Zar, HJ, Koenen, KC, Dalvie, S, Stein, DJ, Kondofersky, I, Mueller, NS, Theis, FJ, Raikkonen, K, Binder, EB, Wray, NR, Ripke, S, Mattheisen, M, Trzaskowski, M, Byrne, EM, Abdellaoui, A, Adams, MJ, Agerbo, E, Air, TM, Andlauer, TFM, Bacanu, S-A, Baekvad-Hansen, M, Beekman, ATF, Bigdeli, TB, Blackwood, DHR, Bryois, J, Buttenschon, HN, Bybjerg-Grauholm, J, Cai, N, Castelao, E, Christensen, JH, Clarke, T-K, Coleman, JR, Colodro-Conde, L, Couvy-Duchesne, B, Craddock, N, Crawford, GE, Davies, G, Deary, IJ, Degenhardt, F, Derks, EM, Direk, N, Dolan, C, Dunn, EC, Eley, TC, Escott-Price, V, Kiadeh, FFH, Finucane, HK, Forstner, AJ, Frank, J, Gaspar, HA, Gill, M, Goes, FS, Gordon, SD, Grove, J, Hall, LS, Hansen, CS, Hansen, TF, Herms, S, Hickie, IB, Hoffmann, P, Homuth, G, Horn, C, Hottenga, J-J, Hougaard, DM, Ising, M, Jansen, R, Jorgenson, E, Knowles, JA, Kohane, IS, Kraft, J, Kretzschmar, WW, Krogh, J, Kutalik, Z, Li, Y, Lind, PA, MacIntyre, DJ, MacKinnon, DF, Maier, RM, Maier, W, Marchini, J, Mbarek, H, McGrath, P, McGuffin, P, Medland, SE, Mehta, D, Middeldorp, CM, Mihailov, E, Milaneschi, Y, Milani, L, Mondimore, FM, Montgomery, GW, Mostafavi, S, Mullins, N, Nauck, M, Ng, B, Nivard, MG, Nyholt, DR, O'Reilly, PF, Oskarsson, H, Owen, MJ, Painter, JN, Pedersen, CB, Pedersen, MG, Peterson, RE, Pettersson, E, Peyrot, WJ, Pistis, G, Posthuma, D, Quiroz, JA, Qvist, P, Rice, JP, Riley, BP, Rivera, M, Mirza, SS, Schoevers, R, Schulte, EC, Shen, L, Shi, J, Shyn, S, Sigurdsson, E, Sinnamon, GCB, Smit, JH, Smith, DJ, Stefansson, H, Steinberg, S, Streit, F, Strohmaier, J, Tansey, KE, Teismann, H, Teumer, A, Thompson, W, Thomson, PA, Thorgeirsson, TE, Traylor, M, Treutlein, J, Trubetskoy, V, Uitterlinden, AG, Umbricht, D, Van der Auwera, S, van Hemert, AM, Viktorin, A, Visscher, PM, Wang, Y, Webb, BT, Weinsheimer, SM, Wellmann, J, Willemsen, G, Witt, SH, Wu, Y, Xi, HS, Yang, J, Zhang, F, Arolt, V, Baune, BT, Berger, K, Boomsma, D, Cichon, S, Dannlowski, U, de Geus, EJC, DePaulo, JR, Domenici, E, Domschke, K, Esko, T, Grabe, HJ, Hamilton, SP, Hayward, C, Heath, AC, Kendler, KS, Kloiber, S, Lewis, G, Li, QS, Lucae, S, Madden, PAF, Magnusson, PK, Martin, NG, McIntosh, AM, Metspalu, A, Mors, O, Mortensen, PB, Mueller-Myhsok, B, Nordentoft, M, Noethen, MM, O'Donovan, MC, Paciga, SA, Pedersen, NL, Penninx, BWJH, Perlis, RH, Porteous, DJ, Potash, JB, Preisig, M, Rietschel, M, Schaefer, C, Schulze, TG, Smoller, JW, Stefansson, K, Tiemeier, H, Uher, R, Voelzke, H, Weissman, MM, Werge, T, Lewis, CM, Levinson, DF, Breen, G, Borglum, AD, and Sullivan, PF

Abstract

Epigenetic processes, including DNA methylation (DNAm), are among the mechanisms allowing integration of genetic and environmental factors to shape cellular function. While many studies have investigated either environmental or genetic contributions to DNAm, few have assessed their integrated effects. Here we examine the relative contributions of prenatal environmental factors and genotype on DNA methylation in neonatal blood at variably methylated regions (VMRs) in 4 independent cohorts (overall n = 2365). We use Akaike's information criterion to test which factors best explain variability of methylation in the cohort-specific VMRs: several prenatal environmental factors (E), genotypes in cis (G), or their additive (G + E) or interaction (GxE) effects. Genetic and environmental factors in combination best explain DNAm at the majority of VMRs. The CpGs best explained by either G, G + E or GxE are functionally distinct. The enrichment of genetic variants from GxE models in GWAS for complex disorders supports their importance for disease risk.

Published
2019

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