Citations 5
Shared genetic risk between eating disorder‐ and substance‐use‐related phenotypes: Evidence from genome‐wide association studies
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E. , Nelson, Elliot C. , Nöthen, Markus M. , Penninx, Brenda W.J.H. , Porjesz, Bernice , Rice, John P. , Rose, Richard J. , Shen, Pei‐Hong , Silberg, Judy L. , Tarter, Ralph E. , Vrieze, Scott , Zhao, Hongyu , Neale, Benjamin M. , Wade, Tracey , Sullivan, Patrick F., Kaprio, Jaakko , Breen, Gerome , Hottenga, Jouke‐Jan , Hakonarson, Hakon , Lissowska, Jolanta , Kennedy, Martin A , Ehrlich, Stefan , Hottenga, Jouke-Jan , Walton, Esther , Cichon, Sven , Luykx, Jurjen J , Nöthen, Markus M , Le Hellard, Stephanie , Penninx, Brenda W J H , Medland, Sarah E , Rabionet, Raquel , Estivil, Xavier , Padyukov, Leonid , Świątkowska, Beata , Dina, Christian , Palotie, Aarno V. , Ripke, Stephan , Whiteman, David C , Scherer, Stephen W , Tortorella, Alfonso , Streit, Fabian , Egberts, Karin , Goate, Alison M , Docherty, Anna R , Johnson, Eric O , Coleman, Jonathan Ri , Johnson, Emma C. , Gordon, Scott D. , Watson, Hunna J. , Gaspar, Héléna A. , Bryois, Julien , Alfredsson, Lars , Andreassen, Ole A. , Boehm, Ilka , Cone, Roger D. , Courtet, Philippe , Crow, Scott J. , Dedoussis, George , Dick, Danielle M. , Dikeos, Dimitris , Escaramís, Geòrgia , Esko, Tõnu , Forzan, Monica , Guillaume, Sébastien , Hauser, Joanna , Herms, Stefan , Herpertz-Dahlmann, Beate , Julià, Antonio , Karhunen, Leila J. , Kennedy, James L. , Li, Dong , Mattingsdal, Morten , Metspalu, Andres , Micali, Nadia , Mitchell, Karen S. , Monteleone, Alessio Maria , Monteleone, Palmiero , Nacmias, Benedetta , Ophoff, Roel A. , Ripatti, Samuli , Roberts, Marion , Santonastaso, Paolo , Scherag, André , Seitz, Jochen , Slagboom, P. Eline , Tenconi, Elena , Τσίτσικα, Άρτεμις , Tyszkiewicz‐Nwafor, Marta , Zeggini, Eleftheria , Boden, Joseph M. , Horwood, L. John , Pearson, John F , Werge, Thomas Mears , Parker, Richard , Lichtenstein, Paul , Norring, Claes E. A. , Mortensen, Preben Bo , Biernacka, Joanna M. , Bigdeli, Tim B. , Clarke, Toni‐Kim , Heilmann‐Heimbach, Stefanie , Hoffmann, Per , Lai, Dongbing , Peterson, Roseann Elizabeth , Sanchez-Roige, Sandra , Schwandt, Melanie L. , Sherva, Richard , Strohmaier, Jana , Thomas, Nathaniel , Wedow, Robbee , Boardman, Jason D., Choi, Doo‐Sup , Degenhardt, Louisa J , Hayward, Caroline , Kramer, John R. , Mann, Karl F , Männistö, Satu , Murray, Alison D. , Nurnberger, John I , Scherbaum, Norbert , Treutlein, Jens , Witt, Stephanie H. , Boomsma, Dorret I , Bierut, Laura Jean , Brown, Sandra A. , Costello, E. Jane , Wit, Harriet de , Eriksson, Johan G. , Farrer, Lindsay A. , Foroud, Tatiana , Gillespie, Nathan A. , Grucza, Richard A. , Harris, Kathleen Mullan , HESSELBROCK, VICTOR M. , Hopfer, Christian Jean , Iacono, William G. , Karpyak, Victor M. , Kendler, Kenneth S. , Kranzler, Henry R. , Palmer, Abraham A. , Rietschel, Marcella , Riley, Brien P. , Stallings, Michael C. , Vanyukov, Michael M. , Wall, Tamara L. , Whitfield, John B. , Heath, Andrew C. , Montgomery, Grant W. , Martin, Nicholas G. , Gelernter, Joel E. , Edenberg, Howard J , Bulik, Cynthia Marie , Agrawal, Arpana , Webb, Bradley T.
Addiction Biology | February 17, 2020 | Volume: 26 | Issue: 1 | Pages: No page available
Abstract Eating disorders and substance use disorders frequently co‐occur. Twin studies reveal shared genetic variance between liabilities to eating disorders and substance use, with the strongest associations between symptoms of bulimia nervosa and problem alcohol use (genetic correlation [ r g ], twin‐based = 0.23‐0.53). We estimated the genetic correlation between eating disorder and substance use and disorder phenotypes using data from genome‐wide association studies (GWAS). Four eating disorder phenotypes (anorexia nervosa [AN], AN with binge eating, AN without binge eating, and a bulimia nervosa factor score), and eight substance‐use‐related phenotypes (drinks per week, alcohol use disorder [AUD], smoking initiation, current smoking, cigarettes per day, nicotine dependence, cannabis initiation, and cannabis use disorder) from eight studies were included. Significant genetic correlations were adjusted for variants associated with major depressive disorder and schizophrenia. Total study sample sizes per phenotype ranged from ~2400 to ~537 000 individuals. We used linkage disequilibrium score regression to calculate single nucleotide polymorphism‐based genetic correlations between eating disorder‐ and substance‐use‐related phenotypes. Significant positive genetic associations emerged between AUD and AN ( r g = 0.18; false discovery rate q = 0.0006), cannabis initiation and AN ( r g = 0.23; q < 0.0001), and cannabis initiation and AN with binge eating ( r g = 0.27; q = 0.0016). Conversely, significant negative genetic correlations were observed between three nondiagnostic smoking phenotypes (smoking initiation, current smoking, and cigarettes per day) and AN without binge eating ( r gs = −0.19 to −0.23; qs < 0.04). The genetic correlation between AUD and AN was no longer significant after co‐varying for major depressive disorder loci. The patterns of association between eating disorder‐ and substance‐use‐related phenotypes highlights the potentially complex and substance‐specific relationships among these behaviors.
Mendelian randomisation implicates hyperlipidaemia as a risk factor for colorectal cancer
Rodriguez‐Broadbent, Henry , Law, Philip , Sud, Amit , Palin, Kimmo , Tuupanen, Sari, Gylfe, Alexandra E., Hänninen, Ulrika A. , Cajuso, Tatiana , Tanskanen, Tomas , Kondelin, Johanna , Kaasinen, Eevi , Sarin, Antti‐Pekka , Rissanen, Harri , Knekt, Paul , Jousilahti, Pekka , Palotie, Aarno , Renkonen‐Sinisalo, Laura , Lepistö, Anna , Böhm, Jan , Mecklin, Jukka‐Pekka , Tassan, Nada Al , Palles, Claire , Martin, Lynn , Barclay, Ella, Farrington, Susan M. , Timofeeva, Maria , Wakil, Salma M. , Campbell, Harry , Idziaszczyk, Shelley, Kaplan, Richard , Kerr, Rachel , Kerr, David , Passarelli, Michael N. , Figueiredo, Jane C. , Buchanan, Daniel D. , Win, Aung Ko , Jenkins, Mark A. , Lindor, Noralane M. , Gallinger, Steven , Conti, David V. , Schumacher, Fredrick R. , Casey, Graham , Aaltonen, Lauri A. , Cheadle, Jeremy P. , Tomlinson, Ian , Dunlop, Malcolm G. , Houlston, Richard S. , Law, Philip J , Buchanan, Daniel D , Win, Aung K , Ripatti, Samuli , Eriksson, Johan G. , Pukkala, Eero , Salomaa, Veikko , Palotie, Aarno V. , Meyer, Brian F. , Smith, Christopher G. , Maughan, Tim , Hopper, John L. , Newcomb, Polly A. , Houlston, Richard S , Jenkins, Mark A , Kaplan, Richard , Kerr, Rachel , Palles, Claire , Conti, David V
International Journal of Cancer | March 25, 2017 | Volume: 140 | Issue: 12 | Pages: 2701-2708
While elevated blood cholesterol has been associated with an increased risk of colorectal cancer (CRC) in observational studies, causality is uncertain. Here we apply a Mendelian randomisation (MR) analysis to examine the potential causal relationship between lipid traits and CRC risk. We used single nucleotide polymorphisms (SNPs) associated with blood levels of total cholesterol (TC), triglyceride (TG), low‐density lipoprotein (LDL), and high‐density lipoprotein (HDL) as instrumental variables (IV). We calculated MR estimates for each risk factor with CRC using SNP‐CRC associations from 9,254 cases and 18,386 controls. Genetically predicted higher TC was associated with an elevated risk of CRC (odds ratios (OR) per unit SD increase = 1.46, 95% confidence interval [CI]: 1.20–1.79, p = 1.68 × 10−4). The pooled ORs for LDL, HDL, and TG were 1.05 (95% CI: 0.92–1.18, p = 0.49), 0.94 (95% CI: 0.84–1.05, p = 0.27), and 0.98 (95% CI: 0.85–1.12, p = 0.75) respectively. A genetic risk score for 3‐hydoxy‐3‐methylglutaryl‐coenzyme A reductase (HMGCR) to mimic the effects of statin therapy was associated with a reduced CRC risk (OR = 0.69, 95% CI: 0.49–0.99, p = 0.046). This study supports a causal relationship between higher levels of TC with CRC risk, and a further rationale for implementing public health strategies to reduce the prevalence of hyperlipidaemia.
Shared Genetic Risk Factors of Intracranial, Abdominal, and Thoracic Aneurysms
Hof, Femke N. G. van ’t, Ruigrok, Ynte M. , Lee, Cue Hyunkyu , Ripke, Stephan , Anderson, Graig, Baas, Annette F., Blankensteijn, Jan D. , Böttinger, Erwin P. , Bown, Matthew J. , Broderick, Joseph P., Bijlenga, Philippe , Crosslin, David R. , Ebeling, Christian , Eriksson, Johan G. , Fornage, Myriam , Foroud, Tatiana, Fraunberg, Mikael von und zu , Friedrich, Christoph M. , Gaál, Emília Ilona, Gottesman, Omri, Guo, Dongchuan , Harrison, Seamus C. , Hernesniemi, Juha , Hofman, Albert , Inoue, Ituro , Jääskeläinen, Juha E. , Kiemeney, Lambertus A. , Kivisaari, Riku , Ko, Nerissa , Koskinen, Seppo, Kubo, Michiaki , Kuivaniemi, Helena , Laakso, Aki , Lehto, Hanna, LeMaire, Scott A. , Malinowski, Jennifer , McCarty, Catherine A. , Mosley, Thomas H., Nakaoka, Hirofumi , Peissig, Peggy , Pera, Joanna , Rasmussen‐Torvik, Laura J. , Ritchie, Marylyn D. , Rivadeneira, Fernando , Rij, André M. van , Santos‐Cortez, Regie Lyn P., Saratzis, Athanasios , Słowik, Agnieszka , Tromp, Gerard , Uitterlinden, André G. , Vermeulen, Sita H. , Wang, Gao T., Han, Buhm , Bakker, Paul I. W. de , Verissimo, Ana Raquel, Wright, Benjamin J., Bumpstead, Suzannah, Grétarsdóttir, Sólveig , Badger, Stephen A., Child, Anne H. , Cockerill, Gillian, Hafez, Hany , Futers, Simon , Sohrabi, Soroush, Smith, Alberto, Thompson, Matthew M., Bockxmeer, Frank M. van, Matthíasson, Stefán E., Þorsteinsdóttir, Unnur , Graaf, Jacqueline de , Palmen, Jutta, Lindholt, Jes S. , Bradley, Declan , Waltham, Matthew, Gwilliam, Rhian, Golledge, Jonathan , Eriksson, Per , Stefánsson, Kāri , Thompson, John R., Humphries, Steve E. , Sayers, Robert D., Deloukas, Panos , Samani, Nilesh J. , Phillip, L. Victoria, Hill, Geraldine B., Williams, Michael , Thomson, Ian , Krysa, Jo, Wilkins, Gerard , Vasudevan, Thodor M., Lewis, David R. , Blair, Ross D., Hill, Andrew A., de Andrade, Mariza, Ripke, Stephan , Andrade, Mariza de , Broderick, Joseph, Carrell, David , Crawford, Dana C. , Jones, Gregory T. , Kullo, Iftikhar J. , Kurki, Mitja , Lai, Dongbing , Leal, Suzanne M. , Low, Siew‐Kee , Milewicz, Dianna M. , Nakamura, Yusuke , Niemela, Mika R. , Pacheco, Jennifer A. , Takahashi, Atsushi , Verma, Shefali S. , Rinkel, Gabriël J.E. , Clough, Rachel E. , Scott, D. Julian A., Þorleifsson, Guðmar , Teijink, Joep A.W. , Wijmenga, Cisca , Smith, Andrew J P , Edkins, Sarah , Hunt, Sarah E , Potter, Simon , Norman, Paul E , Powell, Janet T. , Merriman, Tony Raymond , Kiemeney, Lambertus A , Bijlenga, Philippe , Lindholt, Jes Sanddal , Malinowski, Jennnifer , Rasmussen-Torvik, Laura J , Eriksson, Per
Journal of the American Heart Association | July 15, 2016 | Volume: 5 | Issue: 7 | Pages: No page available
Background Intracranial aneurysms ( IAs ), abdominal aortic aneurysms ( AAAs ), and thoracic aortic aneurysms ( TAAs ) all have a familial predisposition. Given that aneurysm types are known to co‐occur, we hypothesized that there may be shared genetic risk factors for IAs , AAAs, and TAAs . Methods and Results We performed a mega‐analysis of 1000 Genomes Project‐imputed genome‐wide association study ( GWAS ) data of 4 previously published aneurysm cohorts: 2 IA cohorts (in total 1516 cases, 4305 controls), 1 AAA cohort (818 cases, 3004 controls), and 1 TAA cohort (760 cases, 2212 controls), and observed associations of 4 known IA , AAA , and/or TAA risk loci (9p21, 18q11, 15q21, and 2q33) with consistent effect directions in all 4 cohorts. We calculated polygenic scores based on IA ‐, AAA ‐, and TAA ‐associated SNP s and tested these scores for association to case‐control status in the other aneurysm cohorts; this revealed no shared polygenic effects. Similarly, linkage disequilibrium–score regression analyses did not show significant correlations between any pair of aneurysm subtypes. Last, we evaluated the evidence for 14 previously published aneurysm risk single‐nucleotide polymorphisms through collaboration in extended aneurysm cohorts, with a total of 6548 cases and 16 843 controls ( IA ) and 4391 cases and 37 904 controls ( AAA ), and found nominally significant associations for IA risk locus 18q11 near RBBP 8 to AAA (odds ratio [ OR ]=1.11; P =4.1×10 −5 ) and for TAA risk locus 15q21 near FBN 1 to AAA ( OR =1.07; P =1.1×10 −3 ). Conclusions Although there was no evidence for polygenic overlap between IAs , AAAs , and TAAs , we found nominally significant effects of two established risk loci for IAs and TAAs in AAAs . These two loci will require further replication.
DNA mismatch repair gene MSH6 implicated in determining age at natural menopause
Perry, John R. B. , Hsu, Yi-Hsiang, Johnson, Andrew D. , Elks, Cathy E., Albrecht, Eva, Andrulis, Irene L. , Berenson, Gerald S., Bojesen, Stig E. , Bolla, Manjeet K. , Brown, Judith, Buring, Julie E. , Campbell, Harry, Chang‐Claude, Jenny , Chenevix‐Trench, Georgia , Corre, Tanguy , Cox, Angela , Czene, Kamila , D’Adamo, Pio , Davies, Gail , Deary, Ian J. , Easton, Douglas F. , Engelhardt, Ellen G. , Eriksson, Johan G. , Fasching, Peter A. , Figueroa, Jonine D. , Flyger, Henrik, Fraser, Abigail , García‐Closas, Montserrat , Gasparini, Paolo , Gieger, Christian , Giles, Graham G. , Guénel, Pascal , Hägg, Sara , Hayward, Caroline , Hopper, John L. , investigators, kConFab, Kardia, Sharon L. R., Kasiman, Katherine, Knight, Julia A. , Lahti, Jari , Lawlor, Debbie A. , Magnusson, Patrik K. E. , Margolin, Sara , Marsh, Julie , Polašek, Ozren , Rahman, Iffat , Ridker, Paul M., Robino, Antonietta , Rudan, Igor , Salumets, Andres , Schmidt, Marjanka K. , Schoemaker, Minouk J. , Smith, Erin N. , Smith, Jennifer A. , Southey, Melissa C. , Stöckl, Doris, Swerdlow, Anthony J. , Thompson, Deborah J. , Truong, Thérèse , Ulivi, Sheila , Waldenberger, Mélanie , Wang, Qin , Wright, Alan F., Zgaga, Lina , Karasik, David , Murray, Anna , Uitterlinden, André G. , Hsu, Yi‐Hsiang , Chasman, Daniel I. , Beesley, Jonathan , Bergmann, Sven M. , Couch, Fergus J. , Dennis, Joe , Esko, Tõnu , Hall, Per N , Ingelsson, Erik , investigators, kConFab, Metspalu, Andres , Olson, Janet E. , Pennell, Craig Edward , Rudolph, Anja , Wild, Sarah H. , Wilson, James Fox , Ong, Ken K. , Murabito, Joanne M. , Giles, Graham G , Swerdlow, Anthony J , Smith, Jennifer A , Southey, Melissa C , Cox, Angela , Guénel, Pascal , García-Closas, Montserrat , Schmidt, Marjanka K , Chenevix-Trench, Georgia , Figueroa, Jonine D , Czene, Kamila , Bojesen, Stig E , Schoemaker, Minouk J , Truong, Therese
Human Molecular Genetics | December 20, 2013 | Volume: 23 | Issue: 9 | Pages: 2490-2497
GWAS of 126,559 Individuals Identifies Genetic Variants Associated with Educational Attainment
Rietveld, Cornelius A. , Medland, Sarah E. , Derringer, Jaime , Esko, Tõnu , Martín, Nicolás W., Westra, Harm-Jan , Shakhbazov, Konstantin, Abdellaoui, Abdel , Albrecht, Eva, Alizadeh, Behrooz Z. , Amin, Najaf , Baumeister, Sebastian E. , Benke, Kelly S. , Bielak, Lawrence F. , Boatman, Jeffrey A. , Boyle, Patricia A. , Davies, Gail , Leeuw, Christiaan de , Eklund, Niina, Evans, Daniel S. , Ferhmann, Rudolf, Fischer, Krista , Gieger, Christian , Gjessing, Håkon K. , Hägg, Sara , Harris, Jennifer R. , Hayward, Caroline , Jacobsson, Bo , Joshi, Peter K. , Jugessur, Astanand , Kaakinen, Marika , Kanoni, Stavroula , Karjalainen, Juha, Kolčić, Ivana , Kristiansson, Kati , Kutalik, Zoltán , Lahti, Jari , Lee, Sang , Lin, Peng, Lind, Penelope A. , Lohman, Kurt, Loitfelder, Marisa, McMahon, George, Marques‐Vidal, Pedro , Meirelles, Osorio , Milani, Lili , Myhre, Ronny , Nuotio, Marja-Liisa , Oldmeadow, Christopher , Petrovic, Katja, Peyrot, Wouter J. , Polašek, Ozren , Quaye, Lydia, Reinmaa, Eva, Rice, John P. , Rizzi, Thais S., Schmidt, Helena , Schmidt, Reinhold, Smith, Albert V. , Smith, Jennifer A. , Terracciano, Antonio , Loos, Matthijs J. H. M. van der, Vitart, Véronique , Völzke, Henry , Wellmann, Jürgen , Yu, Lei , Zhao, Wei , Allïk, Jüri , Bandinelli, Stefania , Bastardot, François , Beauchamp, Jonathan , Bennett, David A. , Berger, Klaus, Bültmann, Ute , Campbell, Harry, Chabris, Christopher F., Cherkas, Lynn, Chung, Mina K. , Cucca, Francesco , Jager, Philip L. De , Neve, Jan-Emmanuel De, Deary, Ian J. , Dedoussis, George , Deloukas, Panos , Dimitriou, Maria , Eiríksdóttir, Guðný , Elderson, Martin F., Eriksson, Johan G. , Evans, David M. , Faul, Jessica D. , Ferrucci, Luigi , Garcia, Melissa E., Grönberg, Henrik , Guðnason, Vilmundur , Harris, Tamara B., Hastie, Nicholas D. , Hernández, Dena , Hoffmann, Wolfgang , Hofman, Adriaan, Holle, Rolf , Holliday, Elizabeth G., Hottenga, Jouke‐Jan , Illig, Thomas, Järvelin, Marjo‐Riitta , Kähönen, Mika , Kaprio, Jaakko , Kirkpatrick, Robert M. , Kowgier, Matthew , Latvala, Antti , Lawlor, Debbie A. , Lehtimäki, Terho , Li, Jingmei , Lichtenstein, Paul , Lichtner, Peter , Liewald, David C. , Madden, Pamela A. F., Magnusson, Patrik K. E. , Mäkinen, Tomi E., Masala, Marco , McGue, Matt , Mielck, Andreas, Miller, Michael B., Montgomery, Grant W. , Mukherjee, Sutapa , Nyholt, Dale R. , Oostra, Ben A., Palmer, Lyle J. , Palotie, Aarno , Perola, Markus, Peyser, Patricia A. , Preisig, Martin , Räikkönen, Katri , Rivadeneira, Fernando , Rudan, Igor , Rustichini, Aldo , Sarin, Antti-Pekka, Schlessinger, David, Scott, Rodney J. , Snieder, Harold , Pourcain, Beaté St , Starr, John M. , Sul, Jae Hoon , Surakka, Ida , Svento, Rauli , Teumer, Alexander , Study, The LifeLines Cohort, Tiemeier, Henning , Rooij, Frank J.A. van , Wagoner, David R. Van , Vartiainen, Erkki , Viikari, Jorma , Vollenweider, Péter , Vonk, Judith M. , Waeber, Gérard , Weir, David R. , Wichmann, H.‐Erich , Widén, Elisabeth , Willemsen, Gonneke , Wright, Alan F., Davey-Smith, George, Franke, Lude , Groenen, Patrick J. F. , Hofman, Albert , Johannesson, Magnus , Kardia, Sharon L. R., Krueger, Robert F., Laibson, David, Martin, Nicholas G. , Meyer, Michelle N., Posthuma, Daniëlle , Thurik, Roy , Timpson, Nicholas J. , Uitterlinden, André G. , Duijn, Cornelia M. van , Visscher, Peter M. , Benjamin, Daniel J. , Cesarini, David , Koellinger, Philipp , Bennett, David A. , Smith, George Davey , Meyer, Michelle N. , Westra, Harm-Jan , Yang, Jian , Agrawal, Arpana , Barnard, John , Holzapfel, Christina M. , Ibrahim‐Verbaas, Carla A. , Ingelsson, Erik , Lin, Peng, Liu, Ching‐Ti , Tanaka, Toshiko , Attia, John , Berger, Klaus, Bierut, Laura Jean , Boomsma, Dorret I , Andrade, Mariza de , Hall, Per N , Harris, Juliette , Heath, Andrew C. , Hofman, Adriaan, Holliday, Elizabeth G., Iacono, William G. , Launer, Lenore J. , Mäkinen, Tomi E., Metspalu, Andres , Palotie, Aarno V. , Penninx, Brenda W.J.H. , Raitakari, Olli Tuomas , Realo, Anu , Ring, Susan M. , Ripatti, Samuli , Salomaa, Veikko , Study, The LifeLines Cohort, Wilson, James Fox , Conley, Dalton , Davey-Smith, George, Smith, Jennifer A , Hottenga, Jouke-Jan , Martin, Nicholas G , Posthuma, Danielle , St Pourcain, Beate , Medland, Sarah E , Li, Jingmei , Teumer, Alexander , van Duijn, Cornelia M , Smith, Albert V , Ferrucci, Luigi , Davey Smith, George , Vonk, Judith M , Kanoni, Stavroula , Surakka, Ida
Science | May 31, 2013 | Volume: 340 | Issue: 6139 | Pages: 1467-1471
Genetic College Many genomic elements in humans are associated with behavior, including educational attainment. In a genome-wide association study including more than 100,000 samples, Rietveld et al. (p. 1467 , published online 30 May; see the Perspective by Flint and Munafò ) looked for genes related to educational attainment in Caucasians. Small genetic effects at three loci appeared to impact educational attainment.