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5. Polygenic risk of major depressive disorder as a risk factor for venous thromboembolism

Author

Ward, Joey, Le, Ngoc-Quynh, Suryakant, Suryakant, Brody, Jennifer A., Amouyel, Philippe, Boland, Anne, Bown, Rosemary, Cullen, Breda, Debette, Stéphanie, Deleuze, Jean-François, Emmerich, Joseph, Graham, Nicholas, Germain, Marine, Anderson, Jana J., Pell, Jill P., Lyall, Donald M., Lyall, Laura M., Smith, Daniel J., Wiggins, Kerri L., Soria, José Manuel, Souto, Juan Carlos, Morange, Pierre-Emmanuel, Smith, Nicholas L., Trégouët, David-Alexandre, Sabater-Lleal, Maria, and Strawbridge, Rona J.

Published
2023
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14. The overlap of genetic susceptibility to schizophrenia and cardiometabolic disease can be used to identify metabolically different groups of individuals

Author

Strawbridge, Rona J., Johnston, Keira J. A., Bailey, Mark E. S., Baldassarre, Damiano, Cullen, Breda, Eriksson, Per, deFaire, Ulf, Ferguson, Amy, Gigante, Bruna, Giral, Philippe, Graham, Nicholas, Hamsten, Anders, Humphries, Steve E., Kurl, Sudhir, Lyall, Donald M., Lyall, Laura M., Pell, Jill P., Pirro, Matteo, Savonen, Kai, Smit, Andries J., Tremoli, Elena, Tomainen, Tomi-Pekka, Veglia, Fabrizio, Ward, Joey, Sennblad, Bengt, and Smith, Daniel J.

Published
2021
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15. The genomic basis of mood instability: identification of 46 loci in 363,705 UK Biobank participants, genetic correlation with psychiatric disorders, and association with gene expression and function

Author

Ward, Joey, Tunbridge, Elizabeth M., Sandor, Cynthia, Lyall, Laura M., Ferguson, Amy, Strawbridge, Rona J., Lyall, Donald M., Cullen, Breda, Graham, Nicholas, Johnston, Keira J. A., Webber, Caleb, Escott-Price, Valentina, O’Donovan, Michael, Pell, Jill P., Bailey, Mark E. S., Harrison, Paul J., and Smith, Daniel J.

Published
2020
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18. Cognitive Function in People With Familial Risk of Depression

Author

Cullen, Breda, primary, Gameroff, Marc J., additional, Ward, Joey, additional, Bailey, Mark E. S., additional, Lyall, Donald M., additional, Lyall, Laura M., additional, MacSweeney, Niamh, additional, Murphy, Eleanor, additional, Sangha, Natasha, additional, Shen, Xueyi, additional, Strawbridge, Rona J., additional, van Dijk, Milenna T., additional, Zhu, Xingxing, additional, Smith, Daniel J., additional, Talati, Ardesheer, additional, Whalley, Heather C., additional, Cavanagh, Jonathan, additional, and Weissman, Myrna M., additional

Published
2023
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22. Genome-wide meta-analysis of depression identifies 102 independent variants and highlights the importance of the prefrontal brain regions

Author

Howard, David M., Adams, Mark J., Clarke, Toni-Kim, Hafferty, Jonathan D., Gibson, Jude, Shirali, Masoud, Coleman, Jonathan R. I., Hagenaars, Saskia P., Ward, Joey, Wigmore, Eleanor M., Alloza, Clara, Shen, Xueyi, Barbu, Miruna C., Xu, Eileen Y., Whalley, Heather C., Marioni, Riccardo E., Porteous, David J., Davies, Gail, Deary, Ian J., Hemani, Gibran, Berger, Klaus, Teismann, Henning, Rawal, Rajesh, Arolt, Volker, Baune, Bernhard T., Dannlowski, Udo, Domschke, Katharina, Tian, Chao, Hinds, David A., Trzaskowski, Maciej, Byrne, Enda M., Ripke, Stephan, Smith, Daniel J., Sullivan, Patrick F., Wray, Naomi R., Breen, Gerome, Lewis, Cathryn M., and McIntosh, Andrew M.

Published
2019
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24. Investigating the potential impact of PCSK9-inhibitors on mood disorders using eQTL-based Mendelian randomization

Author

Aman, Alisha, Slob, Eric AW, Ward, Joey, Cullen, Breda, Graham, Nicholas, Lyall, Donald M, Sattar, Naveed, Strawbridge, Rona J, Aman, Alisha [0000-0003-4022-5880], Ward, Joey [0000-0003-0951-8511], Strawbridge, Rona J [0000-0001-8506-3585], Apollo - University of Cambridge Repository, and Applied Economics

Subjects
Medicine and health sciences, Depressive Disorder, Major, Multidisciplinary, Biology and life sciences, Mood Disorders, PCSK9 Inhibitors, Quantitative Trait Loci, FOS: Social sciences, Mendelian Randomization Analysis, Polymorphism, Single Nucleotide, Social sciences, Humans, Proprotein Convertase 9, Ubiquitin Thiolesterase, Genome-Wide Association Study, Research Article
Abstract

Funder: National Institute for Health Research (NIHR), Funder: British Heart Foundation, Funder: The Aitchison Family Clinical Research Training Fellowship, Funder: The British Heart Foundation and University of Glasgow PhD studentship, Prescription of PCSK9-inhibitors has increased in recent years but not much is known about its off-target effects. PCSK9-expression is evident in non-hepatic tissues, notably the brain, and genetic variation in the PCSK9 locus has recently been shown to be associated with mood disorder-related traits. We investigated whether PCSK9 inhibition, proxied by a genetic reduction in expression of PCSK9 mRNA, might have a causal adverse effect on mood disorder-related traits. We used genetic variants in the PCSK9 locus associated with reduced PCSK9 expression (eQTLs) in the European population from GTEx v8 and examined the effect on PCSK9 protein levels and three mood disorder-related traits (major depressive disorder, mood instability, and neuroticism), using summary statistics from the largest European ancestry genome-wide association studies. We conducted summary-based Mendelian randomization analyses to estimate the causal effects, and attempted replication using data from eQTLGen, Brain-eMETA, and the CAGE consortium. We found that genetically reduced PCSK9 gene-expression levels were significantly associated with reduced PCSK9 protein levels but not with increased risk of mood disorder-related traits. Further investigation of nearby genes demonstrated that reduced USP24 gene-expression levels was significantly associated with increased risk of mood instability (p-value range = 5.2x10-5-0.03), and neuroticism score (p-value range = 2.9x10-5-0.02), but not with PCSK9 protein levels. Our results suggest that genetic variation in this region acts on mood disorders through a PCSK9-independent pathway, and therefore PCSK9-inhibitors are unlikely to have an adverse impact on mood disorder-related traits.

Published
2023
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25. Head motion in the UK Biobank imaging sub-sample: longitudinal stability, associations with psychological and physical health, and risk of non-useable data

Author

Ward, Joey, primary, Cox, Simon R., additional, Quinn, Terry, additional, Lyall, Laura, additional, Strawbridge, Rona J., additional, Russell, Emma, additional, Pell, Jill, additional, Stewart, William, additional, Cullen, Breda, additional, Whalley, Heather C, additional, and Lyall, Donald M, additional

Published
2023
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27. PCSK9 genetic variants and risk of type 2 diabetes: a mendelian randomisation study

Author

Schmidt, Amand F, Swerdlow, Daniel I, Holmes, Michael V, Patel, Riyaz S, Fairhurst-Hunter, Zammy, Lyall, Donald M, Hartwig, Fernando Pires, Horta, Bernardo Lessa, Hyppönen, Elina, Power, Christine, Moldovan, Max, van Iperen, Erik, Hovingh, G Kees, Demuth, Ilja, Norman, Kristina, Steinhagen-Thiessen, Elisabeth, Demuth, Juri, Bertram, Lars, Liu, Tian, Coassin, Stefan, Willeit, Johann, Kiechl, Stefan, Willeit, Karin, Mason, Dan, Wright, John, Morris, Richard, Wanamethee, Goya, Whincup, Peter, Ben-Shlomo, Yoav, McLachlan, Stela, Price, Jackie F, Kivimaki, Mika, Welch, Catherine, Sanchez-Galvez, Adelaida, Marques-Vidal, Pedro, Nicolaides, Andrew, Panayiotou, Andrie G, Onland-Moret, N Charlotte, van der Schouw, Yvonne T, Matullo, Giuseppe, Fiorito, Giovanni, Guarrera, Simonetta, Sacerdote, Carlotta, Wareham, Nicholas J, Langenberg, Claudia, Scott, Robert, Luan, Jian'an, Bobak, Martin, Malyutina, Sofia, Pająk, Andrzej, Kubinova, Ruzena, Tamosiunas, Abdonas, Pikhart, Hynek, Husemoen, Lise Lotte Nystrup, Grarup, Niels, Pedersen, Oluf, Hansen, Torben, Linneberg, Allan, Simonsen, Kenneth Starup, Cooper, Jackie, Humphries, Steve E, Brilliant, Murray, Kitchner, Terrie, Hakonarson, Hakon, Carrell, David S, McCarty, Catherine A, Kirchner, H Lester, Larson, Eric B, Crosslin, David R, de Andrade, Mariza, Roden, Dan M, Denny, Joshua C, Carty, Cara, Hancock, Stephen, Attia, John, Holliday, Elizabeth, O'Donnell, Martin, Yusuf, Salim, Chong, Michael, Pare, Guillaume, van der Harst, Pim, Said, M Abdullah, Eppinga, Ruben N, Verweij, Niek, Snieder, Harold, Christen, Tim, Mook-Kanamori, Dennis O, Gustafsson, Stefan, Lind, Lars, Ingelsson, Erik, Pazoki, Raha, Franco, Oscar, Hofman, Albert, Uitterlinden, Andre, Dehghan, Abbas, Teumer, Alexander, Baumeister, Sebastian, Dörr, Marcus, Lerch, Markus M, Völker, Uwe, Völzke, Henry, Ward, Joey, Pell, Jill P, Smith, Daniel J, Meade, Tom, Maitland-van der Zee, Anke H, Baranova, Ekaterina V, Young, Robin, Ford, Ian, Campbell, Archie, Padmanabhan, Sandosh, Bots, Michiel L, Grobbee, Diederick E, Froguel, Philippe, Thuillier, Dorothée, Balkau, Beverley, Bonnefond, Amélie, Cariou, Bertrand, Smart, Melissa, Bao, Yanchun, Kumari, Meena, Mahajan, Anubha, Ridker, Paul M, Chasman, Daniel I, Reiner, Alex P, Lange, Leslie A, Ritchie, Marylyn D, Asselbergs, Folkert W, Casas, Juan-Pablo, Keating, Brendan J, Preiss, David, Hingorani, Aroon D, and Sattar, Naveed

Published
2017
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33. Genetic architecture of the HLA/MHC locus in cardiometabolic disease, severe mental illness, and related traits.

Author

Hayman, Madeleine, primary, Nicolson, Katy, additional, Anderson, Jana J, additional, Cullen, Breda, additional, Cavanagh, Jonathan, additional, Ferguson, Lynn D, additional, Graham, Nicholas, additional, Ho, Frederick K, additional, Lyall, Donald M, additional, Lyall, Laura M, additional, Parra-Soto, Solange, additional, Pell, Jill P, additional, Pellicori, Pierpaolo, additional, Siebert, Stefan, additional, Welsh, Paul, additional, Ward, Joey, additional, and Strawbridge, Rona J, additional

Published
2023
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37. Genetic variation in CADM2 as a link between psychological traits and obesity

Author

Morris, Julia, Bailey, Mark E. S., Baldassarre, Damiano, Cullen, Breda, de Faire, Ulf, Ferguson, Amy, Gigante, Bruna, Giral, Philippe, Goel, Anuj, Graham, Nicholas, Hamsten, Anders, Humphries, Steve E., Johnston, Keira J. A., Lyall, Donald M., Lyall, Laura M., Sennblad, Bengt, Silveira, Angela, Smit, Andries J., Tremoli, Elena, Veglia, Fabrizio, Ward, Joey, Watkins, Hugh, Smith, Daniel J., and Strawbridge, Rona J.

Published
2019
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38. Genetics of self-reported risk-taking behaviour, trans-ethnic consistency and relevance to brain gene expression

Author

Strawbridge, Rona J., Ward, Joey, Lyall, Laura M., Tunbridge, Elizabeth M., Cullen, Breda, Graham, Nicholas, Ferguson, Amy, Johnston, Keira J. A., Lyall, Donald M., Mackay, Daniel, Cavanagh, Jonathan, Howard, David M., Adams, Mark J., Deary, Ian, Escott-Price, Valentina, O’Donovan, Michael, McIntosh, Andrew M., Bailey, Mark E. S., Pell, Jill P., Harrison, Paul J., and Smith, Daniel J.

Published
2018
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40. Testing for association between exonic glucagon‐like peptide 1 receptor mutation with physical and brain health traits in UK Biobank

Author

Ward, Joey, primary, Lyall, Laura M., additional, Strawbridge, Rona J., additional, Stanciu, Ioana, additional, Veldsman, Michele, additional, Garfield, Victoria, additional, Celis‐Morales, Carlos, additional, Newby, Danielle, additional, Stewart, William, additional, Pell, Jill P., additional, Sattar, Naveed, additional, and Lyall, Donald M., additional

Published
2022
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43. Correction: The genomic basis of mood instability: identification of 46 loci in 363,705 UK Biobank participants, genetic correlation with psychiatric disorders, and association with gene expression and function

Author

Ward, Joey, Tunbridge, Elizabeth M., Sandor, Cynthia, Lyall, Laura M., Ferguson, Amy, Strawbridge, Rona J., Lyall, Donald M., Cullen, Breda, Graham, Nicholas, Johnston, Keira J. A., Webber, Caleb, Escott-Price, Valentina, O’Donovan, Michael, Pell, Jill P., Bailey, Mark E. S., Harrison, Paul J., and Smith, Daniel J.

Published
2020
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45. Genome-wide analysis of self-reported risk-taking behaviour and cross-disorder genetic correlations in the UK Biobank cohort

Author

Strawbridge, Rona J., Ward, Joey, Cullen, Breda, Tunbridge, Elizabeth M., Hartz, Sarah, Bierut, Laura, Horton, Amy, Bailey, Mark E. S., Graham, Nicholas, Ferguson, Amy, Lyall, Donald M., Mackay, Daniel, Pidgeon, Laura M., Cavanagh, Jonathan, Pell, Jill P., O’Donovan, Michael, Escott-Price, Valentina, Harrison, Paul J., and Smith, Daniel J.

Published
2018
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46. Quantifying bias in psychological and physical health in the UK Biobank imaging sub-sample

Author

Lyall, Donald M., Quinn, Terry, Lyall, Laura M., Ward, Joey, Anderson, Jana J., Smith, Daniel J., Stewart, William, Strawbridge, Rona J., Bailey, Mark E.S., and Cullen, Breda

Subjects
General Engineering
Abstract

UK Biobank is a prospective cohort study of around half-a-million general population participants, recruited between 2006 and 2010, with baseline studies at recruitment and multiple assessments since. From 2014 to date, magnetic resonance imaging (MRI) has been pursued in a participant sub-sample, with the aim to scan around n = 100k. This sub-sample is studied widely and therefore understanding its relative characteristics is important for future reports. We aimed to quantify psychological and physical health in the UK Biobank imaging sub-sample, compared with the rest of the cohort. We used t-tests and χ2 for continuous/categorical variables, respectively, to estimate average differences on a range of cognitive, mental and physical health phenotypes. We contrasted baseline values of participants who attended imaging (versus had not), and compared their values at the imaging visit versus baseline values of participants who were not scanned. We also tested the hypothesis that the associations of established risk factors with worse cognition would be underestimated in the (hypothesized) healthier imaging group compared with the full cohort. We tested these interactions using linear regression models. On a range of cognitive, mental health, cardiometabolic, inflammatory and neurological phenotypes, we found that 47 920 participants who were scanned by January 2021 showed consistent statistically significant ‘healthy’ bias compared with the ∼450 000 who were not scanned. These effect sizes were small to moderate based on Cohen’s d/Cramer’s V metrics (range = 0.02 to −0.21 for Townsend, the largest effect size). We found evidence of interaction, where stratified analysis demonstrated that associations of established cognitive risk factors were smaller in the imaging sub-sample compared with the full cohort. Of the ∼100 000 participants who ultimately will undergo MRI assessment within UK Biobank, the first ∼50 000 showed some ‘healthy’ bias on a range of metrics at baseline. Those differences largely remained at the subsequent (first) imaging visit, and we provide evidence that testing associations in the imaging sub-sample alone could lead to potential underestimation of exposure/outcome estimates.

Published
2022

48. A Genome-Wide Association Analysis of Happiness: Consistent Genetic Effects Across the Lifespan and Across Genetic Ancestries in Multiple Cohorts

Author

Ward, Joey, primary, Lyall, Laura, additional, Cullen, Breda, additional, Strawbridge, Rona J., additional, Zhu, Xingxing, additional, Stanciu, Ioana, additional, Aman, Alisha, additional, Niedzwiedz, Claire L., additional, Anderson, Jana, additional, Bailey, Mark E. S., additional, Lyall, Donald M., additional, and Pell, Jill, additional

Published
2022
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49. Testing for association between exonic glucagon‐like peptide 1 receptor mutation with physical and brain health traits in UK Biobank.

Author

Ward, Joey, Lyall, Laura M., Strawbridge, Rona J., Stanciu, Ioana, Veldsman, Michele, Garfield, Victoria, Celis‐Morales, Carlos, Newby, Danielle, Stewart, William, Pell, Jill P., Sattar, Naveed, and Lyall, Donald M.

Subjects
*GLUCAGON-like peptide-1 receptor, *GLUCAGON-like peptide 1, *BIOBANKS, *SYSTOLIC blood pressure, *DEMENTIA, *GENOTYPES, *BODY mass index, *SINGLE nucleotide polymorphisms
Abstract

Pre-imputation quality control, imputation and post-imputation cleaning were conducted by UK Biobank (described in the UK Biobank release documentation).[10] Locus rs10305492 was directly genotyped [as per all single nucleotide polymorphisms (SNPs) reported herein]. Blood samples were collected at the baseline assessment and DNA extracted, genotyped and quality controlled by the central UK Biobank team.[10] In 2018, UK Biobank released genetic data for 487 409 individuals, genotyped using the Affymetrix UK BiLEVE Axiom or the Affymetrix UK Biobank Axiom arrays (Santa Clara, CA, USA) containing over 95% common content. DATA AVAILABILITY STATEMENT The UK Biobank resource is available to bona fide researchers for health-related research in the public interest. Testing for association between exonic glucagon-like peptide 1 receptor mutation with physical and brain health traits in UK Biobank. [Extracted from the article]

Published
2023
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