Author: "Deary, IJ." - Searchworks@Jio Institute Digital Library Search Results

Your search keyword '"Deary, IJ."' showing total 1,652 results

Start Over Author "Deary, IJ."

1,652 results on '"Deary, IJ."'

1. Associations between total MRI-visible small vessel disease burden and domain-specific cognitive abilities in a community-dwelling older-age cohort

Author: Hamilton, OKL, Cox, SR, Ballerini, L, Bastin, ME, Corley, J, Gow, AJ, Muñoz Maniega, S, Redmond, P, Valdés Hernández, M del C, Wardlaw, JM, and Deary, IJ
Published: 2021
Full Text: View/download PDF

2. Erratum: GWAS meta-analysis reveals novel loci and genetic correlates for general cognitive function: a report from the COGENT consortium

Author: Trampush, JW, Yang, MLZ, Yu, J, Knowles, E, Davies, G, Liewald, DC, Starr, JM, Djurovic, S, Melle, I, Sundet, K, Christoforou, A, Reinvang, I, DeRosse, P, Lundervold, AJ, Steen, VM, Espeseth, T, Räikkönen, K, Widen, E, Palotie, A, Eriksson, JG, Giegling, I, Konte, B, Roussos, P, Giakoumaki, S, Burdick, KE, Payton, A, Ollier, W, Horan, M, Chiba-Falek, O, Attix, DK, Need, AC, Cirulli, ET, Voineskos, AN, Stefanis, NC, Avramopoulos, D, Hatzimanolis, A, Arking, DE, Smyrnis, N, Bilder, RM, Freimer, NA, Cannon, TD, London, E, Poldrack, RA, Sabb, FW, Congdon, E, Conley, ED, Scult, MA, Dickinson, D, Straub, RE, Donohoe, G, Morris, D, Corvin, A, Gill, M, Hariri, AR, Weinberger, DR, Pendleton, N, Bitsios, P, Rujescu, D, Lahti, J, Le Hellard, S, Keller, MC, Andreassen, OA, Deary, IJ, Glahn, DC, Malhotra, AK, and Lencz, T
Subjects: Biomedical and Clinical Sciences, Biological Psychology, Clinical and Health Psychology, Clinical Sciences, Psychology, Genetics, Biotechnology, Aetiology, 2.1 Biological and endogenous factors, Good Health and Well Being, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry, Clinical sciences, Biological psychology, Clinical and health psychology
Abstract: This corrects the article DOI: 10.1038/mp.2016.244.
Published: 2017

3. GWAS meta-analysis reveals novel loci and genetic correlates for general cognitive function: a report from the COGENT consortium.

Author: Trampush, JW, Yang, MLZ, Yu, J, Knowles, E, Davies, G, Liewald, DC, Starr, JM, Djurovic, S, Melle, I, Sundet, K, Christoforou, A, Reinvang, I, DeRosse, P, Lundervold, AJ, Steen, VM, Espeseth, T, Räikkönen, K, Widen, E, Palotie, A, Eriksson, JG, Giegling, I, Konte, B, Roussos, P, Giakoumaki, S, Burdick, KE, Payton, A, Ollier, W, Horan, M, Chiba-Falek, O, Attix, DK, Need, AC, Cirulli, ET, Voineskos, AN, Stefanis, NC, Avramopoulos, D, Hatzimanolis, A, Arking, DE, Smyrnis, N, Bilder, RM, Freimer, NA, Cannon, TD, London, E, Poldrack, RA, Sabb, FW, Congdon, E, Conley, ED, Scult, MA, Dickinson, D, Straub, RE, Donohoe, G, Morris, D, Corvin, A, Gill, M, Hariri, AR, Weinberger, DR, Pendleton, N, Bitsios, P, Rujescu, D, Lahti, J, Le Hellard, S, Keller, MC, Andreassen, OA, Deary, IJ, Glahn, DC, Malhotra, AK, and Lencz, T
Subjects: Psychiatry, Medical and Health Sciences, Biological Sciences, Psychology and Cognitive Sciences
Abstract: This corrects the article DOI: 10.1038/mp.2016.244.
Published: 2017

4. Genomics of perivascular space burden unravels early mechanisms of cerebral small vessel disease.

Author: Duperron, M-G, Knol, MJ, Le Grand, Q, Evans, TE, Mishra, A, Tsuchida, A, Roshchupkin, G, Konuma, T, Trégouët, D-A, Romero, JR, Frenzel, S, Luciano, M, Hofer, E, Bourgey, M, Dueker, ND, Delgado, P, Hilal, S, Tankard, RM, Dubost, F, Shin, J, Saba, Y, Armstrong, NJ, Bordes, C, Bastin, ME, Beiser, A, Brodaty, H, Bülow, R, Carrera, C, Chen, C, Cheng, C-Y, Deary, IJ, Gampawar, PG, Himali, JJ, Jiang, J, Kawaguchi, T, Li, S, Macalli, M, Marquis, P, Morris, Z, Muñoz Maniega, S, Miyamoto, S, Okawa, M, Paradise, M, Parva, P, Rundek, T, Sargurupremraj, M, Schilling, S, Setoh, K, Soukarieh, O, Tabara, Y, Teumer, A, Thalamuthu, A, Trollor, JN, Valdés Hernández, MC, Vernooij, MW, Völker, U, Wittfeld, K, Wong, TY, Wright, MJ, Zhang, J, Zhao, W, Zhu, Y-C, Schmidt, H, Sachdev, PS, Wen, W, Yoshida, K, Joutel, A, Satizabal, CL, Sacco, RL, Bourque, G, CHARGE consortium, Lathrop, M, Paus, T, Fernandez-Cadenas, I, Yang, Q, Mazoyer, B, Boutinaud, P, Okada, Y, Grabe, HJ, Mather, KA, Schmidt, R, Joliot, M, Ikram, MA, Matsuda, F, Tzourio, C, Wardlaw, JM, Seshadri, S, Adams, HHH, Debette, S, Duperron, M-G, Knol, MJ, Le Grand, Q, Evans, TE, Mishra, A, Tsuchida, A, Roshchupkin, G, Konuma, T, Trégouët, D-A, Romero, JR, Frenzel, S, Luciano, M, Hofer, E, Bourgey, M, Dueker, ND, Delgado, P, Hilal, S, Tankard, RM, Dubost, F, Shin, J, Saba, Y, Armstrong, NJ, Bordes, C, Bastin, ME, Beiser, A, Brodaty, H, Bülow, R, Carrera, C, Chen, C, Cheng, C-Y, Deary, IJ, Gampawar, PG, Himali, JJ, Jiang, J, Kawaguchi, T, Li, S, Macalli, M, Marquis, P, Morris, Z, Muñoz Maniega, S, Miyamoto, S, Okawa, M, Paradise, M, Parva, P, Rundek, T, Sargurupremraj, M, Schilling, S, Setoh, K, Soukarieh, O, Tabara, Y, Teumer, A, Thalamuthu, A, Trollor, JN, Valdés Hernández, MC, Vernooij, MW, Völker, U, Wittfeld, K, Wong, TY, Wright, MJ, Zhang, J, Zhao, W, Zhu, Y-C, Schmidt, H, Sachdev, PS, Wen, W, Yoshida, K, Joutel, A, Satizabal, CL, Sacco, RL, Bourque, G, CHARGE consortium, Lathrop, M, Paus, T, Fernandez-Cadenas, I, Yang, Q, Mazoyer, B, Boutinaud, P, Okada, Y, Grabe, HJ, Mather, KA, Schmidt, R, Joliot, M, Ikram, MA, Matsuda, F, Tzourio, C, Wardlaw, JM, Seshadri, S, Adams, HHH, and Debette, S
Abstract: Perivascular space (PVS) burden is an emerging, poorly understood, magnetic resonance imaging marker of cerebral small vessel disease, a leading cause of stroke and dementia. Genome-wide association studies in up to 40,095 participants (18 population-based cohorts, 66.3 ± 8.6 yr, 96.9% European ancestry) revealed 24 genome-wide significant PVS risk loci, mainly in the white matter. These were associated with white matter PVS already in young adults (N = 1,748; 22.1 ± 2.3 yr) and were enriched in early-onset leukodystrophy genes and genes expressed in fetal brain endothelial cells, suggesting early-life mechanisms. In total, 53% of white matter PVS risk loci showed nominally significant associations (27% after multiple-testing correction) in a Japanese population-based cohort (N = 2,862; 68.3 ± 5.3 yr). Mendelian randomization supported causal associations of high blood pressure with basal ganglia and hippocampal PVS, and of basal ganglia PVS and hippocampal PVS with stroke, accounting for blood pressure. Our findings provide insight into the biology of PVS and cerebral small vessel disease, pointing to pathways involving extracellular matrix, membrane transport and developmental processes, and the potential for genetically informed prioritization of drug targets.
Published: 2023

5. Reproducibility in the absence of selective reporting: An illustration from large-scale brain asymmetry research

Author: Kong, XZ, Francks, C, Mathias, SR, Guadalupe, T, Abé, C, Agartz, I, Akudjedu, TN, Aleman, A, Alhusaini, S, Allen, NB, Ames, D, Andreassen, OA, Vasquez, AA, Armstrong, NJ, Asherson, P, Bergo, F, Bastin, ME, Batalla, A, Bauer, J, Baune, BT, Baur-Streubel, R, Biederman, J, Blaine, SK, Boedhoe, P, Bøen, E, Bose, A, Bralten, J, Brandeis, D, Brem, S, Brodaty, H, Yüksel, D, Brooks, SJ, Buitelaar, J, Bürger, C, Bülow, R, Calhoun, V, Calvo, A, Canales-Rodríguez, EJ, Cannon, DM, Caparelli, EC, Castellanos, FX, Cendes, F, Chaim-Avancini, TM, Chantiluke, K, Chen, QL, Chen, X, Cheng, Y, Christakou, A, Clark, VP, Coghill, D, Connolly, CG, Conzelmann, A, Córdova-Palomera, A, Cousijn, J, Crow, T, Cubillo, A, Dannlowski, U, de Bruttopilo, SA, de Zeeuw, P, Deary, IJ, Demeter, DV, Di Martino, A, Dickie, EW, Dietsche, B, Doan, NT, Doherty, CP, Doyle, A, Durston, S, Earl, E, Ehrlich, S, Ekman, CJ, Elvsåshagen, T, Epstein, JN, Fair, DA, Faraone, SV, Fernández, G, Flint, C, Filho, GB, Förster, K, Fouche, JP, Foxe, JJ, Frodl, T, Fuentes-Claramonte, P, Fullerton, JM, Garavan, H, do Santos Garcia, D, Gotlib, IH, Goudriaan, AE, Grabe, HJ, Groenewold, NA, Grotegerd, D, Gruber, O, Gurholt, T, Haavik, J, Hahn, T, Hansell, NK, Harris, MA, Hartman, CA, del Carmen Valdés Hernández, M, Kong, XZ, Francks, C, Mathias, SR, Guadalupe, T, Abé, C, Agartz, I, Akudjedu, TN, Aleman, A, Alhusaini, S, Allen, NB, Ames, D, Andreassen, OA, Vasquez, AA, Armstrong, NJ, Asherson, P, Bergo, F, Bastin, ME, Batalla, A, Bauer, J, Baune, BT, Baur-Streubel, R, Biederman, J, Blaine, SK, Boedhoe, P, Bøen, E, Bose, A, Bralten, J, Brandeis, D, Brem, S, Brodaty, H, Yüksel, D, Brooks, SJ, Buitelaar, J, Bürger, C, Bülow, R, Calhoun, V, Calvo, A, Canales-Rodríguez, EJ, Cannon, DM, Caparelli, EC, Castellanos, FX, Cendes, F, Chaim-Avancini, TM, Chantiluke, K, Chen, QL, Chen, X, Cheng, Y, Christakou, A, Clark, VP, Coghill, D, Connolly, CG, Conzelmann, A, Córdova-Palomera, A, Cousijn, J, Crow, T, Cubillo, A, Dannlowski, U, de Bruttopilo, SA, de Zeeuw, P, Deary, IJ, Demeter, DV, Di Martino, A, Dickie, EW, Dietsche, B, Doan, NT, Doherty, CP, Doyle, A, Durston, S, Earl, E, Ehrlich, S, Ekman, CJ, Elvsåshagen, T, Epstein, JN, Fair, DA, Faraone, SV, Fernández, G, Flint, C, Filho, GB, Förster, K, Fouche, JP, Foxe, JJ, Frodl, T, Fuentes-Claramonte, P, Fullerton, JM, Garavan, H, do Santos Garcia, D, Gotlib, IH, Goudriaan, AE, Grabe, HJ, Groenewold, NA, Grotegerd, D, Gruber, O, Gurholt, T, Haavik, J, Hahn, T, Hansell, NK, Harris, MA, Hartman, CA, and del Carmen Valdés Hernández, M
Published: 2022

6. Genome-wide interaction study with major depression identifies novel variants associated with cognitive function

Author: Thalamuthu, A, Mills, NT, Berger, K, Minnerup, H, Grotegerd, D, Dannlowski, U, Meinert, S, Opel, N, Repple, J, Gruber, M, Stein, F, Brosch, K, Meller, T, Pfarr, J-K, Forstner, AJ, Hoffmann, P, Nothen, MM, Witt, S, Rietschel, M, Kircher, T, Adams, M, McIntosh, AM, Porteous, DJ, Deary, IJ, Hayward, C, Campbell, A, Grabe, HJ, Teumer, A, Homuth, G, Van der Auwera-Palitschka, S, Schubert, KO, Baune, BT, Thalamuthu, A, Mills, NT, Berger, K, Minnerup, H, Grotegerd, D, Dannlowski, U, Meinert, S, Opel, N, Repple, J, Gruber, M, Stein, F, Brosch, K, Meller, T, Pfarr, J-K, Forstner, AJ, Hoffmann, P, Nothen, MM, Witt, S, Rietschel, M, Kircher, T, Adams, M, McIntosh, AM, Porteous, DJ, Deary, IJ, Hayward, C, Campbell, A, Grabe, HJ, Teumer, A, Homuth, G, Van der Auwera-Palitschka, S, Schubert, KO, and Baune, BT
Abstract: Major Depressive Disorder (MDD) often is associated with significant cognitive dysfunction. We conducted a meta-analysis of genome-wide interaction of MDD and cognitive function using data from four large European cohorts in a total of 3510 MDD cases and 6057 controls. In addition, we conducted analyses using polygenic risk scores (PRS) based on data from the Psychiatric Genomics Consortium (PGC) on the traits of MDD, Bipolar disorder (BD), Schizophrenia (SCZ), and mood instability (MIN). Functional exploration contained gene expression analyses and Ingenuity Pathway Analysis (IPA®). We identified a set of significantly interacting single nucleotide polymorphisms (SNPs) between MDD and the genome-wide association study (GWAS) of cognitive domains of executive function, processing speed, and global cognition. Several of these SNPs are located in genes expressed in brain, with important roles such as neuronal development (REST), oligodendrocyte maturation (TNFRSF21), and myelination (ARFGEF1). IPA® identified a set of core genes from our dataset that mapped to a wide range of canonical pathways and biological functions (MPO, FOXO1, PDE3A, TSLP, NLRP9, ADAMTS5, ROBO1, REST). Furthermore, IPA® identified upstream regulator molecules and causal networks impacting on the expression of dataset genes, providing a genetic basis for further clinical exploration (vitamin D receptor, beta-estradiol, tadalafil). PRS of MIN and meta-PRS of MDD, MIN and SCZ were significantly associated with all cognitive domains. Our results suggest several genes involved in physiological processes for the development and maintenance of cognition in MDD, as well as potential novel therapeutic agents that could be explored in patients with MDD associated cognitive dysfunction.
Published: 2022

7. Genome-wide meta-analyses reveal novel loci for verbal short-term memory and learning

Author: Lahti, J, Tuominen, S, Yang, Q, Pergola, G, Ahmad, S, Amin, N, Armstrong, NJ, Beiser, A, Bey, K, Bis, JC, Boerwinkle, E, Bressler, J, Campbell, A, Campbell, H, Chen, Q, Corley, J, Cox, SR, Davies, G, De Jager, PL, Derks, EM, Faul, JD, Fitzpatrick, AL, Fohner, AE, Ford, I, Fornage, M, Gerring, Z, Grabe, HJ, Grodstein, F, Gudnason, V, Simonsick, E, Holliday, EG, Joshi, PK, Kajantie, E, Kaprio, J, Karell, P, Kleineidam, L, Knol, MJ, Kochan, NA, Kwok, JB, Leber, M, Lam, M, Lee, T, Li, S, Loukola, A, Luck, T, Marioni, RE, Mather, KA, Medland, S, Mirza, SS, Nalls, MA, Nho, K, O'Donnell, A, Oldmeadow, C, Painter, J, Pattie, A, Reppermund, S, Risacher, SL, Rose, RJ, Sadashivaiah, V, Scholz, M, Satizabal, CL, Schofield, PW, Schraut, KE, Scott, RJ, Simino, J, Smith, AV, Smith, JA, Stott, DJ, Surakka, I, Teumer, A, Thalamuthu, A, Trompet, S, Turner, ST, van der Lee, SJ, Villringer, A, Voelker, U, Wilson, RS, Wittfeld, K, Vuoksimaa, E, Xia, R, Yaffe, K, Yu, L, Zare, H, Zhao, W, Ames, D, Attia, J, Bennett, DA, Brodaty, H, Chasman, DI, Goldman, AL, Hayward, C, Ikram, MA, Jukema, JW, Kardia, SLR, Lencz, T, Loeffler, M, Mattay, VS, Palotie, A, Psaty, BM, Ramirez, A, Ridker, PM, Riedel-Heller, SG, Sachdev, PS, Saykin, AJ, Scherer, M, Schofield, PR, Sidney, S, Starr, JM, Trollor, J, Ulrich, W, Wagner, M, Weir, DR, Wilson, JF, Wright, MJ, Weinberger, DR, Debette, S, Eriksson, JG, Mosley, TH, Launer, LJ, van Duijn, CM, Deary, IJ, Seshadri, S, Raikkonen, K, Lahti, J, Tuominen, S, Yang, Q, Pergola, G, Ahmad, S, Amin, N, Armstrong, NJ, Beiser, A, Bey, K, Bis, JC, Boerwinkle, E, Bressler, J, Campbell, A, Campbell, H, Chen, Q, Corley, J, Cox, SR, Davies, G, De Jager, PL, Derks, EM, Faul, JD, Fitzpatrick, AL, Fohner, AE, Ford, I, Fornage, M, Gerring, Z, Grabe, HJ, Grodstein, F, Gudnason, V, Simonsick, E, Holliday, EG, Joshi, PK, Kajantie, E, Kaprio, J, Karell, P, Kleineidam, L, Knol, MJ, Kochan, NA, Kwok, JB, Leber, M, Lam, M, Lee, T, Li, S, Loukola, A, Luck, T, Marioni, RE, Mather, KA, Medland, S, Mirza, SS, Nalls, MA, Nho, K, O'Donnell, A, Oldmeadow, C, Painter, J, Pattie, A, Reppermund, S, Risacher, SL, Rose, RJ, Sadashivaiah, V, Scholz, M, Satizabal, CL, Schofield, PW, Schraut, KE, Scott, RJ, Simino, J, Smith, AV, Smith, JA, Stott, DJ, Surakka, I, Teumer, A, Thalamuthu, A, Trompet, S, Turner, ST, van der Lee, SJ, Villringer, A, Voelker, U, Wilson, RS, Wittfeld, K, Vuoksimaa, E, Xia, R, Yaffe, K, Yu, L, Zare, H, Zhao, W, Ames, D, Attia, J, Bennett, DA, Brodaty, H, Chasman, DI, Goldman, AL, Hayward, C, Ikram, MA, Jukema, JW, Kardia, SLR, Lencz, T, Loeffler, M, Mattay, VS, Palotie, A, Psaty, BM, Ramirez, A, Ridker, PM, Riedel-Heller, SG, Sachdev, PS, Saykin, AJ, Scherer, M, Schofield, PR, Sidney, S, Starr, JM, Trollor, J, Ulrich, W, Wagner, M, Weir, DR, Wilson, JF, Wright, MJ, Weinberger, DR, Debette, S, Eriksson, JG, Mosley, TH, Launer, LJ, van Duijn, CM, Deary, IJ, Seshadri, S, and Raikkonen, K
Abstract: Understanding the genomic basis of memory processes may help in combating neurodegenerative disorders. Hence, we examined the associations of common genetic variants with verbal short-term memory and verbal learning in adults without dementia or stroke (N = 53,637). We identified novel loci in the intronic region of CDH18, and at 13q21 and 3p21.1, as well as an expected signal in the APOE/APOC1/TOMM40 region. These results replicated in an independent sample. Functional and bioinformatic analyses supported many of these loci and further implicated POC1. We showed that polygenic score for verbal learning associated with brain activation in right parieto-occipital region during working memory task. Finally, we showed genetic correlations of these memory traits with several neurocognitive and health outcomes. Our findings suggest a role of several genomic loci in verbal memory processes.
Published: 2022

8. Association analyses identify 31 new risk loci for colorectal cancer susceptibility

Author: Law, PJ, Timofeeva, M, Fernandez-Rozadilla, C, Broderick, P, Studd, J, Fernandez-Tajes, J, Farrington, S, Svinti, V, Palles, C, Orlando, G, Sud, A, Holroyd, A, Penegar, S, Theodoratou, E, Vaughan-Shaw, P, Campbell, H, Zgaga, L, Hayward, C, Campbell, A, Harris, S, Deary, IJ, Starr, J, Gatcombe, L, Pinna, M, Briggs, S, Martin, L, Jaeger, E, Sharma-Oates, A, East, J, Leedham, S, Arnold, R, Johnstone, E, Wang, H, Kerr, D, Kerr, R, Maughan, T, Kaplan, R, Al-Tassan, N, Palin, K, Hänninen, UA, Cajuso, T, Tanskanen, T, Kondelin, J, Kaasinen, E, Sarin, A-P, Eriksson, JG, Rissanen, H, Knekt, P, Pukkala, E, Jousilahti, P, Salomaa, V, Ripatti, S, Palotie, A, Renkonen-Sinisalo, L, Lepistö, A, Böhm, J, Mecklin, J-P, Buchanan, DD, Win, A-K, Hopper, J, Jenkins, ME, Lindor, NM, Newcomb, PA, Gallinger, S, Duggan, D, Casey, G, Hoffmann, P, Nöthen, MM, Jöckel, K-H, Easton, DF, Pharoah, PDP, Peto, J, Canzian, F, Swerdlow, A, Eeles, RA, Kote-Jarai, Z, Muir, K, Pashayan, N, Consortium, Practical, Harkin, A, Allan, K, McQueen, J, Paul, J, Iveson, T, Saunders, M, Butterbach, K, Chang-Claude, J, Hoffmeister, M, Brenner, H, Kirac, I, Matošević, P, Hofer, P, Brezina, S, Gsur, A, Cheadle, JP, Aaltonen, LA, Tomlinson, I, Houlston, RS, Dunlop, MG, Law, Philip J [0000-0001-9663-4611], Timofeeva, Maria [0000-0002-2503-4253], Fernandez-Rozadilla, Ceres [0000-0001-7330-4804], Broderick, Peter [0000-0002-8348-5829], Studd, James [0000-0002-7157-754X], Farrington, Susan [0000-0001-5955-7389], Svinti, Victoria [0000-0001-9926-0416], Sud, Amit [0000-0002-6133-0164], Hayward, Caroline [0000-0002-9405-9550], Campbell, Archie [0000-0003-0198-5078], Martin, Lynn [0000-0003-3962-389X], East, James [0000-0001-8035-3700], Kaplan, Richard [0000-0002-0189-8348], Al-Tassan, Nada [0000-0001-9076-0334], Palin, Kimmo [0000-0002-4621-6128], Salomaa, Veikko [0000-0001-7563-5324], Buchanan, Daniel D [0000-0003-2225-6675], Win, Aung-Ko [0000-0002-2794-5261], Jenkins, Mark E [0000-0002-8964-6160], Easton, Douglas F [0000-0003-2444-3247], Pharoah, Paul DP [0000-0001-8494-732X], Eeles, Rosalind A [0000-0002-3698-6241], Muir, Kenneth [0000-0001-6429-988X], Pashayan, Nora [0000-0003-0843-2468], Harkin, Andrea [0000-0002-8831-7381], Paul, James [0000-0001-7367-5816], Hofer, Philipp [0000-0003-2550-6019], Brezina, Stefanie [0000-0001-5238-6900], Cheadle, Jeremy P [0000-0001-9453-8458], Tomlinson, Ian [0000-0003-3037-1470], Houlston, Richard S [0000-0002-5268-0242], and Apollo - University of Cambridge Repository
Subjects: Male, Science, Inheritance Patterns, cancer genetics, Datasets as Topic, colorectal cancer, Genome-wide association studies, Polymorphism, Single Nucleotide, Article, White People, Asian People, Risk Factors, Cancer genomics, Humans, Genetic Predisposition to Disease, lcsh:Science, Cancer genetics, neoplasms, cancer genomics, genomiikka, Middle Aged, Colorectal cancer, digestive system diseases, peräsuolisyöpä, syöpägeenit, Genetic Loci, Case-Control Studies, genome-wide association studies, lcsh:Q, syöpätaudit, Female, Colorectal Neoplasms, Genome-Wide Association Study
Abstract: Colorectal cancer (CRC) is a leading cause of cancer-related death worldwide, and has a strong heritable basis. We report a genome-wide association analysis of 34,627 CRC cases and 71,379 controls of European ancestry that identifies SNPs at 31 new CRC risk loci. We also identify eight independent risk SNPs at the new and previously reported European CRC loci, and a further nine CRC SNPs at loci previously only identified in Asian populations. We use in situ promoter capture Hi-C (CHi-C), gene expression, and in silico annotation methods to identify likely target genes of CRC SNPs. Whilst these new SNP associations implicate target genes that are enriched for known CRC pathways such as Wnt and BMP, they also highlight novel pathways with no prior links to colorectal tumourigenesis. These findings provide further insight into CRC susceptibility and enhance the prospects of applying genetic risk scores to personalised screening and prevention., In colorectal cancer (CRC), finding loci associated with risk may give insight into disease aetiology. Here, the authors report a genome-wide association analysis in Europeans of 34,627 CRC cases and 71,379 controls, and find 31 new risk loci and 17 new risk SNPs at previously reported loci.
Published: 2019

9. Publisher Correction:Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals

Author: Surendran, P, Feofanova, EV, Lahrouchi, N, Ntalla, I, Karthikeyan, S, Cook, J, Chen, L, Mifsud, B, Yao, C, Kraja, AT, Cartwright, JH, Hellwege, JN, Giri, A, Tragante, V, Thorleifsson, G, Liu, DJ, Prins, BP, Stewart, ID, Cabrera, CP, Eales, JM, Akbarov, A, Auer, PL, Bielak, LF, Bis, JC, Braithwaite, VS, Brody, JA, Daw, EW, Warren, HR, Drenos, F, Nielsen, SF, Faul, JD, Fauman, EB, Fava, C, Ferreira, T, Foley, CN, Franceschini, N, Gao, H, Giannakopoulou, O, Giulianini, F, Gudbjartsson, DF, Guo, X, Harris, SE, Havulinna, AS, Helgadottir, A, Huffman, JE, Hwang, S-J, Kanoni, S, Kontto, J, Larson, MG, Li-Gao, R, Lindstrom, J, Lotta, LA, Lu, Y, Luan, J, Mahajan, A, Malerba, G, Masca, NGD, Mei, H, Menni, C, Mook-Kanamori, DO, Mosen-Ansorena, D, Muller-Nurasyid, M, Pare, G, Paul, DS, Perola, M, Poveda, A, Rauramaa, R, Richard, M, Richardson, TG, Sepulveda, N, Sim, X, Smith, AV, Smith, JA, Staley, JR, Stanakova, A, Sulem, P, Theriault, S, Thorsteinsdottir, U, Trompet, S, Varga, TV, Velez Edwards, DR, Veronesi, G, Weiss, S, Willems, SM, Yao, J, Young, R, Yu, B, Zhang, W, Zhao, J-H, Zhao, W, Evangelou, E, Aeschbacher, S, Asllanaj, E, Blankenberg, S, Bonnycastle, LL, Bork-Jensen, J, Brandslund, I, Braund, PS, Burgess, S, Cho, K, Christensen, C, Connell, J, De Mutsert, R, Dominiczak, AF, Dorr, M, Eiriksdottir, G, Farmaki, A-E, Gaziano, JM, Grarup, N, Grove, ML, Hallmans, G, Hansen, T, Have, CT, Heiss, G, Jorgensen, ME, Jousilahti, P, Kajantie, E, Kamat, M, Karajamaki, A, Karpe, F, Koistinen, HA, Kovesdy, CP, Kuulasmaa, K, Laatikainen, I, Lannfelt, L, Lee, I-T, Lee, W-J, Linneberg, A, Martin, LW, Moitry, M, Nadkarni, G, Neville, MJ, Palmer, CNA, Papanicolaou, GJ, Pedersen, O, Peters, J, Poulter, N, Rasheed, A, Rasmussen, KL, Rayner, NW, Magi, R, Renstrom, F, Rettig, R, Rossouw, J, Schreiner, PJ, Sever, PS, Sigurdsson, EL, Skaaby, T, Sun, YV, Sundstrom, J, Thorgeirsson, G, Esko, T, Trabetti, E, Tsao, PS, Tuomi, T, Turner, ST, Tzoulaki, I, Vaartjes, I, Vergnaud, A-C, Willer, CJ, Wilson, PWF, Witte, DR, Yonova-Doing, E, Zhang, H, Aliya, N, Almgren, P, Amouyel, P, Asselbergs, FW, Barnes, MR, Blakemore, AI, Boehnke, M, Bots, ML, Bottinger, EP, Buring, JE, Chambers, JC, Chen, Y-DI, Chowdhury, R, Conen, D, Correa, A, Davey Smith, G, Boer, RAD, Deary, IJ, Dedoussis, G, Deloukas, P, Di Angelantonio, E, Elliott, P, Felix, SB, Ferrieres, J, Ford, I, Fornage, M, Franks, PW, Franks, S, Frossard, P, Gambaro, G, Gaunt, TR, Groop, L, Gudnason, V, Harris, TB, Hayward, C, Hennig, BJ, Herzig, K-H, Ingelsson, E, Tuomilehto, J, Jarvelin, M-R, Jukema, JW, Kardia, SLR, Kee, F, Kooner, JS, Kooperberg, C, Launer, LJ, Lind, L, Loos, RJF, Majumder, AAS, Laakso, M, McCarthy, MI, Melander, O, Mohlke, KL, Murray, AD, Nordestgaard, BG, Orho-Melander, M, Packard, CJ, Padmanabhan, S, Palmas, W, Polasek, O, Porteous, DJ, Prentice, AM, Province, MA, Relton, CL, Rice, K, Ridker, PM, Rolandsson, O, Rosendaal, FR, Rotter, JI, Rudan, I, Salomaa, V, Samani, NJ, Sattar, N, Sheu, WH-H, Smith, BH, Soranzo, N, Spector, TD, Starr, JM, Sebert, S, Taylor, KD, Lakka, TA, Timpson, NJ, Tobin, MD, Van der Harst, P, Van der Meer, P, Ramachandran, VS, Verweij, N, Virtamo, J, Volker, U, Weir, DR, Zeggini, E, Charchar, FJ, Wareham, NJ, Langenberg, C, Tomaszewski, M, Butterworth, AS, Caulfield, MJ, Danesh, J, Edwards, TL, Holm, H, Hung, AM, Lindgren, CM, Liu, C, Manning, AK, Morris, AP, Morrison, AC, O'Donnell, CJ, Psaty, BM, Saleheen, D, Stefansson, K, Boerwinkle, E, Chasman, DI, Levy, D, Newton-Cheh, C, Munroe, PB, Howson, JMM, and United Kingdom Research and Innovation
Subjects: Genetics & Heredity, Understanding Society Scientific Group, Science & Technology, business.industry, Published Erratum, Million Veteran Program, MEDLINE, Computational biology, 06 Biological Sciences, Biology, Blood pressure, Text mining, Meta-analysis, EPIC-InterAct, Genetics, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, business, Life Sciences & Biomedicine, EPIC-CVD, 11 Medical and Health Sciences, LifeLines Cohort Study, Developmental Biology
Abstract: In the version of this article originally published, the e-mail address of corresponding author Patricia B. Munroe was incorrect. The error has been corrected in the HTML and PDF versions of the article.
Published: 2021
Full Text: View/download PDF

10. Genome-Wide Association Study of Circulating Interleukin 6 Levels Identifies Novel Loci

Author: Ahluwalia, TS, Prins, BP, Abdollahi, M, Armstrong, NJ, Aslibekyan, S, Bain, L, Jefferis, B, Baumert, J, Beekman, M, Ben-Shlomo, Y, Bis, JC, Mitchell, BD, de Geus, E, Delgado, GE, Marek, D, Eriksson, J, Kajantie, E, Kanoni, S, Kemp, JP, Lu, C, Marioni, RE, McLachlan, S, Milaneschi, Y, Nolte, IM, Petrelis, AM, Porcu, E, Sabater-Lleal, M, Naderi, E, Seppälä, I, Shah, T, Singhal, G, Standl, M, Teumer, A, Thalamuthu, A, Thiering, E, Trompet, S, Ballantyne, CM, Benjamin, EJ, Casas, JP, Toben, C, Dedoussis, G, Deelen, J, Durda, P, Engmann, J, Feitosa, MF, Grallert, H, Hammarstedt, A, Harris, SE, Homuth, G, Hottenga, J-J, Jalkanen, S, Jamshidi, Y, Jawahar, MC, Jess, T, Kivimaki, M, Kleber, ME, Lahti, J, Liu, Y, Marques-Vidal, P, Mellström, D, Mooijaart, SP, Müller-Nurasyid, M, Penninx, B, Revez, JA, Rossing, P, Räikkönen, K, Sattar, N, Scharnagl, H, Sennblad, B, Silveira, A, Pourcain, BS, Timpson, NJ, Trollor, J, CHARGE Inflammation Working Group, van Dongen, J, Van Heemst, D, Visvikis-Siest, S, Vollenweider, P, Völker, U, Waldenberger, M, Willemsen, G, Zabaneh, D, Morris, RW, Arnett, DK, Baune, BT, Boomsma, DI, Chang, Y-PC, Deary, IJ, Deloukas, P, Eriksson, JG, Evans, DM, Ferreira, MA, Gaunt, T, Gudnason, V, Hamsten, A, Heinrich, J, Hingorani, A, Humphries, SE, Jukema, JW, Koeing, W, Kumari, M, Kutalik, Z, Lawlor, DA, Lehtimäki, T, März, W, Mather, K, Naitza, S, Nauck, M, Ohlsson, C, Price, JF, Raitakari, O, Rice, K, Sachdev, PS, Slagboom, E, Sørensen, TIA, Spector, T, Stacey, D, Stathopoulou, MG, Tanaka, T, Wannamethee, SG, Whincup, P, Rotter, JI, Dehghan, A, Boerwinkle, E, Psaty, BM, Snieder, H, and Alizadeh, BZ
Abstract: Interleukin-6 (IL-6) is a multifunctional cytokine with both pro- and anti-inflammatory properties with a heritability estimate of up to 61%. The circulating levels of IL-6 in blood have been associated with an increased risk of complex disease pathogenesis. We conducted a two-staged, discovery, and replication meta genome-wide association study (GWAS) of circulating serum IL-6 levels comprising up to 67 428 (ndiscovery = 52 654 and nreplication = 14 774) individuals of European ancestry. The inverse variance fixed-effects based discovery meta-analysis, followed by replication led to the identification of two independent loci, IL1F10/IL1RN rs6734238 on Chromosome (Chr) 2q14, (pcombined = 1.8 × 10-11), HLA-DRB1/DRB5 rs660895 on Chr6p21 (pcombined = 1.5 × 10-10) in the combined meta-analyses of all samples. We also replicated the IL6R rs4537545 locus on Chr1q21 (pcombined = 1.2 × 10-122). Our study identifies novel loci for circulating IL-6 levels uncovering new immunological and inflammatory pathways that may influence IL-6 pathobiology.
Published: 2021

11. Variants associated with HHIP expression have sexdifferential effects on lung function

Author: Fawcett, KA, Obeidat, M, Melbourne, C, Shrine, N, Guyatt, AL, John, C, Luan, J, Richmond, A, Moksnes, MR, Granell, R, Weiss, S, Imboden, M, May-Wilson, S, Hysi, P, Boutin, TS, Portas, L, Flexeder, C, Harris, SE, Wang, CA, Lyytikäinen, LP, Palviainen, T, Foong, RE, Keidel, D, Minelli, C, Langenberg, C, Bossé, Y, Berge, MVD, Sin, DD, Hao, K, Campbell, A, Porteous, D, Padmanabhan, S, Smith, BH, Evans, DM, Ring, S, Langhammer, A, Hveem, K, Willer, C, Ewert, R, Stubbe, B, Pirastu, N, Klaric, L, Joshi, PK, Patasova, K, Massimo, M, Polasek, O, Starr, JM, Karrasch, S, Strauch, K, Meitinger, T, Rudan, I, Rantanen, T, Pietiläinen, K, Kähönen, M, Raitakari, OT, Hall, GL, Sly, Peter, Pennell, CE, Kaprio, J, Lehtimäki, T, Vitart, V, Deary, IJ, Jarvis, D, Wilson, JF, Spector, T, Probst-Hensch, N, Wareham, NJ, Völzke, H, Henderson, J, Strachan, DP, Brumpton, BM, Hayward, C, Hall, IP, Tobin, MD, Wain, LV, Fawcett, KA, Obeidat, M, Melbourne, C, Shrine, N, Guyatt, AL, John, C, Luan, J, Richmond, A, Moksnes, MR, Granell, R, Weiss, S, Imboden, M, May-Wilson, S, Hysi, P, Boutin, TS, Portas, L, Flexeder, C, Harris, SE, Wang, CA, Lyytikäinen, LP, Palviainen, T, Foong, RE, Keidel, D, Minelli, C, Langenberg, C, Bossé, Y, Berge, MVD, Sin, DD, Hao, K, Campbell, A, Porteous, D, Padmanabhan, S, Smith, BH, Evans, DM, Ring, S, Langhammer, A, Hveem, K, Willer, C, Ewert, R, Stubbe, B, Pirastu, N, Klaric, L, Joshi, PK, Patasova, K, Massimo, M, Polasek, O, Starr, JM, Karrasch, S, Strauch, K, Meitinger, T, Rudan, I, Rantanen, T, Pietiläinen, K, Kähönen, M, Raitakari, OT, Hall, GL, Sly, Peter, Pennell, CE, Kaprio, J, Lehtimäki, T, Vitart, V, Deary, IJ, Jarvis, D, Wilson, JF, Spector, T, Probst-Hensch, N, Wareham, NJ, Völzke, H, Henderson, J, Strachan, DP, Brumpton, BM, Hayward, C, Hall, IP, Tobin, MD, and Wain, LV
Published: 2021

12. Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging

Author: McCartney, DL, Min, JL, Richmond, RC, Lu, AT, Sobczyk, MK, Davies, G, Broer, L, Guo, X, Jeong, A, Jung, J, Kasela, S, Katrinli, S, Kuo, P-L, Matias-Garcia, PR, Mishra, PP, Nygaard, M, Palviainen, T, Patki, A, Raffield, LM, Ratliff, SM, Richardson, TG, Robinson, O, Soerensen, M, Sun, D, Tsai, P-C, van der Zee, MD, Walker, RM, Wang, X, Wang, Y, Xia, R, Xu, Z, Yao, J, Zhao, W, Correa, A, Boerwinkle, E, Dugue, P-A, Durda, P, Elliott, HR, Gieger, C, de Geus, EJC, Harris, SE, Hemani, G, Imboden, M, Kahonen, M, Kardia, SLR, Kresovich, JK, Li, S, Lunetta, KL, Mangino, M, Mason, D, McIntosh, AM, Mengel-From, J, Moore, AZ, Murabito, JM, Ollikainen, M, Pankow, JS, Pedersen, NL, Peters, A, Polidoro, S, Porteous, DJ, Raitakari, O, Rich, SS, Sandler, DP, Sillanpaa, E, Smith, AK, Southey, MC, Strauch, K, Tiwari, H, Tanaka, T, Tillin, T, Uitterlinden, AG, van den Berg, DJ, van Dongen, J, Wilson, JG, Wright, J, Yet, I, Arnett, D, Bandinelli, S, Bell, JT, Binder, AM, Boomsma, DI, Chen, W, Christensen, K, Conneely, KN, Elliott, P, Ferrucci, L, Fornage, M, Hagg, S, Hayward, C, Irvin, M, Kaprio, J, Lawlor, DA, Lehtimaki, T, Lohoff, FW, Milani, L, Milne, RL, Probst-Hensch, N, Reiner, AP, Ritz, B, Rotter, J, Smith, JA, Taylor, JA, van Meurs, JBJ, Vineis, P, Waldenberger, M, Deary, IJ, Relton, CL, Horvath, S, Marioni, RE, McCartney, DL, Min, JL, Richmond, RC, Lu, AT, Sobczyk, MK, Davies, G, Broer, L, Guo, X, Jeong, A, Jung, J, Kasela, S, Katrinli, S, Kuo, P-L, Matias-Garcia, PR, Mishra, PP, Nygaard, M, Palviainen, T, Patki, A, Raffield, LM, Ratliff, SM, Richardson, TG, Robinson, O, Soerensen, M, Sun, D, Tsai, P-C, van der Zee, MD, Walker, RM, Wang, X, Wang, Y, Xia, R, Xu, Z, Yao, J, Zhao, W, Correa, A, Boerwinkle, E, Dugue, P-A, Durda, P, Elliott, HR, Gieger, C, de Geus, EJC, Harris, SE, Hemani, G, Imboden, M, Kahonen, M, Kardia, SLR, Kresovich, JK, Li, S, Lunetta, KL, Mangino, M, Mason, D, McIntosh, AM, Mengel-From, J, Moore, AZ, Murabito, JM, Ollikainen, M, Pankow, JS, Pedersen, NL, Peters, A, Polidoro, S, Porteous, DJ, Raitakari, O, Rich, SS, Sandler, DP, Sillanpaa, E, Smith, AK, Southey, MC, Strauch, K, Tiwari, H, Tanaka, T, Tillin, T, Uitterlinden, AG, van den Berg, DJ, van Dongen, J, Wilson, JG, Wright, J, Yet, I, Arnett, D, Bandinelli, S, Bell, JT, Binder, AM, Boomsma, DI, Chen, W, Christensen, K, Conneely, KN, Elliott, P, Ferrucci, L, Fornage, M, Hagg, S, Hayward, C, Irvin, M, Kaprio, J, Lawlor, DA, Lehtimaki, T, Lohoff, FW, Milani, L, Milne, RL, Probst-Hensch, N, Reiner, AP, Ritz, B, Rotter, J, Smith, JA, Taylor, JA, van Meurs, JBJ, Vineis, P, Waldenberger, M, Deary, IJ, Relton, CL, Horvath, S, and Marioni, RE
Abstract: BACKGROUND: Biological aging estimators derived from DNA methylation data are heritable and correlate with morbidity and mortality. Consequently, identification of genetic and environmental contributors to the variation in these measures in populations has become a major goal in the field. RESULTS: Leveraging DNA methylation and SNP data from more than 40,000 individuals, we identify 137 genome-wide significant loci, of which 113 are novel, from genome-wide association study (GWAS) meta-analyses of four epigenetic clocks and epigenetic surrogate markers for granulocyte proportions and plasminogen activator inhibitor 1 levels, respectively. We find evidence for shared genetic loci associated with the Horvath clock and expression of transcripts encoding genes linked to lipid metabolism and immune function. Notably, these loci are independent of those reported to regulate DNA methylation levels at constituent clock CpGs. A polygenic score for GrimAge acceleration showed strong associations with adiposity-related traits, educational attainment, parental longevity, and C-reactive protein levels. CONCLUSION: This study illuminates the genetic architecture underlying epigenetic aging and its shared genetic contributions with lifestyle factors and longevity.
Published: 2021

13. Epigenome-wide meta-analysis of blood DNA methylation and its association with subcortical volumes: findings from the ENIGMA Epigenetics Working Group

Author: Jia, T, Chu, C, Liu, Y, van Dongen, J, Papastergios, E, Armstrong, NJ, Bastin, ME, Carrillo-Roa, T, den Braber, A, Harris, M, Jansen, R, Liu, J, Luciano, M, Ori, APS, Santianez, RR, Ruggeri, B, Sarkisyan, D, Shin, J, Sungeun, K, Gutierrez, DT, van't Ent, D, Ames, D, Artiges, E, Bakalkin, G, Banaschewski, T, Bokde, ALW, Brodaty, H, Bromberg, U, Brouwer, R, Buchel, C, Quinlan, EB, Cahn, W, de Zubicaray, G, Ehrlich, S, Ekstrom, TJ, Flor, H, Frohner, JH, Frouin, V, Garavan, H, Gowland, P, Heinz, A, Hoare, J, Ittermann, B, Jahanshad, N, Jiang, J, Kwok, JB, Martin, NG, Martinot, J-L, Mather, KA, McMahon, KL, McRae, AF, Nees, F, Orfanos, DP, Paus, T, Poustka, L, Samann, PG, Schofield, PR, Smolka, MN, Stein, DJ, Strike, LT, Teeuw, J, Thalamuthu, A, Trollor, J, Walter, H, Wardlaw, JM, Wen, W, Whelan, R, Apostolova, LG, Binder, EB, Boomsma, D, Calhoun, V, Crespo-Facorro, B, Deary, IJ, Pol, HH, Ophoff, RA, Pausova, Z, Sachdev, PS, Saykin, A, Wright, MJ, Thompson, PM, Schumann, G, Desrivieres, S, Jia, T, Chu, C, Liu, Y, van Dongen, J, Papastergios, E, Armstrong, NJ, Bastin, ME, Carrillo-Roa, T, den Braber, A, Harris, M, Jansen, R, Liu, J, Luciano, M, Ori, APS, Santianez, RR, Ruggeri, B, Sarkisyan, D, Shin, J, Sungeun, K, Gutierrez, DT, van't Ent, D, Ames, D, Artiges, E, Bakalkin, G, Banaschewski, T, Bokde, ALW, Brodaty, H, Bromberg, U, Brouwer, R, Buchel, C, Quinlan, EB, Cahn, W, de Zubicaray, G, Ehrlich, S, Ekstrom, TJ, Flor, H, Frohner, JH, Frouin, V, Garavan, H, Gowland, P, Heinz, A, Hoare, J, Ittermann, B, Jahanshad, N, Jiang, J, Kwok, JB, Martin, NG, Martinot, J-L, Mather, KA, McMahon, KL, McRae, AF, Nees, F, Orfanos, DP, Paus, T, Poustka, L, Samann, PG, Schofield, PR, Smolka, MN, Stein, DJ, Strike, LT, Teeuw, J, Thalamuthu, A, Trollor, J, Walter, H, Wardlaw, JM, Wen, W, Whelan, R, Apostolova, LG, Binder, EB, Boomsma, D, Calhoun, V, Crespo-Facorro, B, Deary, IJ, Pol, HH, Ophoff, RA, Pausova, Z, Sachdev, PS, Saykin, A, Wright, MJ, Thompson, PM, Schumann, G, and Desrivieres, S
Abstract: DNA methylation, which is modulated by both genetic factors and environmental exposures, may offer a unique opportunity to discover novel biomarkers of disease-related brain phenotypes, even when measured in other tissues than brain, such as blood. A few studies of small sample sizes have revealed associations between blood DNA methylation and neuropsychopathology, however, large-scale epigenome-wide association studies (EWAS) are needed to investigate the utility of DNA methylation profiling as a peripheral marker for the brain. Here, in an analysis of eleven international cohorts, totalling 3337 individuals, we report epigenome-wide meta-analyses of blood DNA methylation with volumes of the hippocampus, thalamus and nucleus accumbens (NAcc)-three subcortical regions selected for their associations with disease and heritability and volumetric variability. Analyses of individual CpGs revealed genome-wide significant associations with hippocampal volume at two loci. No significant associations were found for analyses of thalamus and nucleus accumbens volumes. Cluster-based analyses revealed additional differentially methylated regions (DMRs) associated with hippocampal volume. DNA methylation at these loci affected expression of proximal genes involved in learning and memory, stem cell maintenance and differentiation, fatty acid metabolism and type-2 diabetes. These DNA methylation marks, their interaction with genetic variants and their impact on gene expression offer new insights into the relationship between epigenetic variation and brain structure and may provide the basis for biomarker discovery in neurodegeneration and neuropsychiatric conditions.
Published: 2021

14. Rare and low-frequency exonic variants and gene-by-smoking interactions in pulmonary function

Author: Yang, T, Jackson, VE, Smith, A, Chen, H, Bartz, TM, Sitlani, CM, Psaty, BM, Gharib, SA, O'Connor, GT, Dupuis, J, Xu, J, Lohman, K, Liu, Y, Kritchevsky, SB, Cassano, PA, Flexeder, C, Gieger, C, Karrasch, S, Peters, A, Schulz, H, Harris, SE, Starr, JM, Deary, IJ, Manichaikul, A, Oelsner, EC, Barr, RG, Taylor, KD, Rich, SS, Bonten, TN, Mook-Kanamori, DO, Noordam, R, Li-Gao, R, Jarvelin, M-R, Wielscher, M, Terzikhan, N, Lahousse, L, Brusselle, G, Weiss, S, Ewert, R, Glaeser, S, Homuth, G, Shrine, N, Hall, IP, Tobin, M, London, SJ, Wei, P, Morrison, AC, Yang, T, Jackson, VE, Smith, A, Chen, H, Bartz, TM, Sitlani, CM, Psaty, BM, Gharib, SA, O'Connor, GT, Dupuis, J, Xu, J, Lohman, K, Liu, Y, Kritchevsky, SB, Cassano, PA, Flexeder, C, Gieger, C, Karrasch, S, Peters, A, Schulz, H, Harris, SE, Starr, JM, Deary, IJ, Manichaikul, A, Oelsner, EC, Barr, RG, Taylor, KD, Rich, SS, Bonten, TN, Mook-Kanamori, DO, Noordam, R, Li-Gao, R, Jarvelin, M-R, Wielscher, M, Terzikhan, N, Lahousse, L, Brusselle, G, Weiss, S, Ewert, R, Glaeser, S, Homuth, G, Shrine, N, Hall, IP, Tobin, M, London, SJ, Wei, P, and Morrison, AC
Abstract: Genome-wide association studies have identified numerous common genetic variants associated with spirometric measures of pulmonary function, including forced expiratory volume in one second (FEV1), forced vital capacity, and their ratio. However, variants with lower minor allele frequencies are less explored. We conducted a large-scale gene-smoking interaction meta-analysis on exonic rare and low-frequency variants involving 44,429 individuals of European ancestry in the discovery stage and sought replication in the UK BiLEVE study with 45,133 European ancestry samples and UK Biobank study with 59,478 samples. We leveraged data on cigarette smoking, the major environmental risk factor for reduced lung function, by testing gene-by-smoking interaction effects only and simultaneously testing the genetic main effects and interaction effects. The most statistically significant signal that replicated was a previously reported low-frequency signal in GPR126, distinct from common variant associations in this gene. Although only nominal replication was obtained for a top rare variant signal rs142935352 in one of the two studies, interaction and joint tests for current smoking and PDE3B were significantly associated with FEV1. This study investigates the utility of assessing gene-by-smoking interactions and underscores their effects on potential pulmonary function.
Published: 2021

15. DNA methylation of blood cells is associated with prevalent type 2 diabetes in a meta-analysis of four European cohorts

Author: Juvinao-Quintero, DL, Marioni, RE, Ochoa Rosales, Carolina, Russ, TC, Deary, IJ, van Meurs, Joyce, Voortman, Trudy, Hivert, MF, Sharp, GC, Relton, CL, Elliott, HR, Juvinao-Quintero, DL, Marioni, RE, Ochoa Rosales, Carolina, Russ, TC, Deary, IJ, van Meurs, Joyce, Voortman, Trudy, Hivert, MF, Sharp, GC, Relton, CL, and Elliott, HR
Abstract: Background: Type 2 diabetes (T2D) is a heterogeneous disease with well-known genetic and environmental risk factors contributing to its prevalence. Epigenetic mechanisms related to changes in DNA methylation (DNAm), may also contribute to T2D risk, but larger studies are required to discover novel markers, and to confirm existing ones. Results: We performed a large meta-analysis of individual epigenome-wide association studies (EWAS) of prevalent T2D conducted in four European studies using peripheral blood DNAm. Analysis of differentially methylated regions (DMR) was also undertaken, based on the meta-analysis results. We found three novel CpGs associated with prevalent T2D in Europeans at cg00144180 (HDAC4), cg16765088 (near SYNM) and cg24704287 (near MIR23A) and confirmed three CpGs previously identified (mapping to TXNIP, ABCG1 and CPT1A). We also identified 77 T2D associated DMRs, most of them hypomethylated in T2D cases versus controls. In adjusted regressions among diabetic-free participants in ALSPAC, we found that all six CpGs identified in the meta-EWAS were associated with white cell-types. We estimated that these six CpGs captured 11% of the variation in T2D, which was similar to the variation explained by the model including only the common risk factors of BMI, sex, age and smoking (R2 = 10.6%). Conclusions: This study identifies novel loci associated with T2D in Europeans. We also demonstrate associations of the same loci with other traits. Future studies should investigate if our findings are generalizable in non-European populations, and potential roles of these epigenetic markers in T2D etiology or in determining long term consequences of T2D.
Published: 2021

16. Identifying nootropic drug targets via large-scale cognitive GWAS and transcriptomics

Author: Lam, M, Chen, CY, Ge, T, Xia, Y, Hill, DW, Trampush, JW, Yu, J, Knowles, E, Davies, G, Stahl, EA, Huckins, L, Liewald, DC, Djurovic, S, Melle, I, Christoforou, A, Reinvang, I, DeRosse, P, Lundervold, AJ, Steen, VM, Espeseth, T, Räikkönen, K, Widen, E, Palotie, A, Eriksson, JG, Giegling, I, Konte, B, Hartmann, AM, Roussos, P, Giakoumaki, S, Burdick, KE, Payton, A, Ollier, W, Chiba-Falek, O, Koltai, DC, Need, AC, Cirulli, ET, Voineskos, AN, Stefanis, NC, Avramopoulos, D, Hatzimanolis, A, Smyrnis, N, Bilder, RM, Freimer, NB, Cannon, TD, London, E, Poldrack, RA, Sabb, FW, Congdon, E, Conley, ED, Scult, MA, Dickinson, D, Straub, RE, Donohoe, G, Morris, D, Corvin, A, Gill, M, Hariri, AR, Weinberger, DR, Pendleton, N, Bitsios, P, Rujescu, D, Lahti, J, Le Hellard, S, Keller, MC, Andreassen, OA, Deary, IJ, Glahn, DC, Huang, H, Liu, C, Malhotra, AK, Lencz, T, Lam, M, Chen, CY, Ge, T, Xia, Y, Hill, DW, Trampush, JW, Yu, J, Knowles, E, Davies, G, Stahl, EA, Huckins, L, Liewald, DC, Djurovic, S, Melle, I, Christoforou, A, Reinvang, I, DeRosse, P, Lundervold, AJ, Steen, VM, Espeseth, T, Räikkönen, K, Widen, E, Palotie, A, Eriksson, JG, Giegling, I, Konte, B, Hartmann, AM, Roussos, P, Giakoumaki, S, Burdick, KE, Payton, A, Ollier, W, Chiba-Falek, O, Koltai, DC, Need, AC, Cirulli, ET, Voineskos, AN, Stefanis, NC, Avramopoulos, D, Hatzimanolis, A, Smyrnis, N, Bilder, RM, Freimer, NB, Cannon, TD, London, E, Poldrack, RA, Sabb, FW, Congdon, E, Conley, ED, Scult, MA, Dickinson, D, Straub, RE, Donohoe, G, Morris, D, Corvin, A, Gill, M, Hariri, AR, Weinberger, DR, Pendleton, N, Bitsios, P, Rujescu, D, Lahti, J, Le Hellard, S, Keller, MC, Andreassen, OA, Deary, IJ, Glahn, DC, Huang, H, Liu, C, Malhotra, AK, and Lencz, T
Abstract: Broad-based cognitive deficits are an enduring and disabling symptom for many patients with severe mental illness, and these impairments are inadequately addressed by current medications. While novel drug targets for schizophrenia and depression have emerged from recent large-scale genome-wide association studies (GWAS) of these psychiatric disorders, GWAS of general cognitive ability can suggest potential targets for nootropic drug repurposing. Here, we (1) meta-analyze results from two recent cognitive GWAS to further enhance power for locus discovery; (2) employ several complementary transcriptomic methods to identify genes in these loci that are credibly associated with cognition; and (3) further annotate the resulting genes using multiple chemoinformatic databases to identify “druggable” targets. Using our meta-analytic data set (N = 373,617), we identified 241 independent cognition-associated loci (29 novel), and 76 genes were identified by 2 or more methods of gene identification. Actin and chromatin binding gene sets were identified as novel pathways that could be targeted via drug repurposing. Leveraging our transcriptomic and chemoinformatic databases, we identified 16 putative genes targeted by existing drugs potentially available for cognitive repurposing.
Published: 2021

17. Meta-analysis of up to 622,409 individuals identifies 40 novel smoking behaviour associated genetic loci

Author: Erzurumluoglu, AM, Liu, M, Jackson, VE, Barnes, DR, Datta, G, Melbourne, CA, Young, R, Batini, C, Surendran, P, Jiang, T, Adnan, SD, Afaq, S, Agrawal, A, Altmaier, E, Antoniou, AC, Asselbergs, FW, Baumbach, C, Beirut, L, Bertelsen, S, Boehnke, M, Bots, ML, Brazel, DM, Chambers, JC, Chang-Claude, J, Chen, C, Corley, J, Chou, Y-L, David, SP, de Boer, RA, de Leeuw, CA, Dennis, JG, Dominiczak, AF, Dunning, AM, Easton, DF, Eaton, C, Elliott, P, Evangelou, E, Faul, JD, Foroud, T, Goate, A, Gong, J, Grabe, HJ, Haessler, J, Haiman, C, Hallmans, G, Hammerschlag, AR, Harris, SE, Hattersley, A, Heath, A, Hsu, C, Iacono, WG, Kanoni, S, Kapoor, M, Kaprio, J, Kardia, SL, Karpe, F, Kontto, J, Kooner, JS, Kooperberg, C, Kuulasmaa, K, Laakso, M, Lai, D, Langenberg, C, Le, N, Lettre, G, Loukola, A, Luan, J, Madden, PAF, Mangino, M, Marioni, RE, Marouli, E, Marten, J, Martin, NG, McGue, M, Michailidou, K, Mihailov, E, Moayyeri, A, Moitry, M, Müller-Nurasyid, M, Naheed, A, Nauck, M, Neville, MJ, Nielsen, SF, North, K, Perola, M, Pharoah, PDP, Pistis, G, Polderman, TJ, Posthuma, D, Poulter, N, Qaiser, B, Rasheed, A, Reiner, A, Renström, F, Rice, J, Rohde, R, Rolandsson, O, Samani, NJ, Samuel, M, Schlessinger, D, Scholte, SH, Scott, RA, Sever, P, Shao, Y, Shrine, N, Smith, JA, Starr, JM, Stirrups, K, Stram, D, Stringham, HM, Tachmazidou, I, Tardif, J-C, Thompson, DJ, Tindle, HA, Tragante, V, Trompet, S, Turcot, V, Tyrrell, J, Vaartjes, I, van der Leij, AR, van der Meer, P, Varga, TV, Verweij, N, Völzke, H, Wareham, NJ, Warren, HR, Weir, DR, Weiss, S, Wetherill, L, Yaghootkar, H, Yavas, E, Jiang, Y, Chen, F, Zhan, X, Zhang, W, Zhao, W, Zhou, K, Amouyel, P, Blankenberg, S, Caulfield, MJ, Chowdhury, R, Cucca, F, Deary, IJ, Deloukas, P, Di Angelantonio, E, Ferrario, M, Ferrières, J, Franks, PW, Frayling, TM, Frossard, P, Hall, IP, Hayward, C, Jansson, J-H, Jukema, JW, Kee, F, Männistö, S, Metspalu, A, Munroe, PB, Nordestgaard, BG, Palmer, CNA, Salomaa, V, Sattar, N, Spector, T, Strachan, DP, Understanding Society Scientific Group, EPIC-CVD, GSCAN, Consortium for Genetics of Smoking Behaviour, CHD Exome+ Consortium, van der Harst, P, Zeggini, E, Saleheen, D, Butterworth, AS, Wain, LV, Abecasis, GR, Danesh, J, Tobin, MD, Vrieze, S, Liu, DJ, and Howson, JMM
Abstract: Smoking is a major heritable and modifiable risk factor for many diseases, including cancer, common respiratory disorders and cardiovascular diseases. Fourteen genetic loci have previously been associated with smoking behaviour-related traits. We tested up to 235,116 single nucleotide variants (SNVs) on the exome-array for association with smoking initiation, cigarettes per day, pack-years, and smoking cessation in a fixed effects meta-analysis of up to 61 studies (up to 346,813 participants). In a subset of 112,811 participants, a further one million SNVs were also genotyped and tested for association with the four smoking behaviour traits. SNV-trait associations with P
Published: 2020

18. Variants associated with HHIP expression have sex-differential effects on lung function [version 1; peer review: 2 approved]

Author: Fawcett, KA, Obeidat, M, Melbourne, C, Shrine, N, Guyatt, AL, John, C, Luan, J, Richmond, A, Moksnes, MR, Granell, R, Weiss, S, Imboden, M, May-Wilson, S, Hysi, P, Boutin, TS, Portas, L, Flexeder, C, Harris, SE, Wang, CA, Lyytikäinen, LP, Palviainen, T, Foong, RE, Keidel, D, Minelli, C, Langenberg, C, Bossé, Y, Van den Berge, M, Sin, DD, Hao, K, Campbell, A, Porteous, D, Padmanabhan, S, Smith, BH, Evans, DM, Ring, S, Langhammer, A, Hveem, K, Willer, C, Ewert, R, Stubbe, B, Pirastu, N, Klaric, L, Joshi, PK, Patasova, K, Massimo, M, Polasek, O, Starr, JM, Karrasch, S, Strauch, K, Meitinger, T, Rudan, I, Rantanen, T., Pietiläinen, K, Kähönen, M, Raitakari, OT, Hall, GL, Sly, PD, Pennell, CE, Kaprio, J, Lehtimäki, T, Vitart, V, Deary, IJ, Jarvis, D, Wilson, JF, Spector, T, Probst-Hensch, N, Wareham, NJ, Völzke, H, Henderson, J, Strachan, DP, Brumpton, BM, Hayward, C, Hall, IP, Tobin, MD, and Wain, LV
Subjects: genome-wide interaction study, HHIP, lcsh:R, lcsh:Medicine, lung function, genotyyppi, sukupuoli, hengityselimet, toimintakyky, expression, sex, lcsh:Q, geeniekspressio, geneettiset tekijät, lcsh:Science, keuhkot
Abstract: Background: Lung function is highly heritable and differs between the sexes throughout life. However, little is known about sex-differential genetic effects on lung function. We aimed to conduct the first genome-wide genotype-by-sex interaction study on lung function to identify genetic effects that differ between males and females. Methods: We tested for interactions between 7,745,864 variants and sex on spirometry-based measures of lung function in UK Biobank (N=303,612), and sought replication in 75,696 independent individuals from the SpiroMeta consortium. Results: Five independent single-nucleotide polymorphisms (SNPs) showed genome-wide significant (P
Published: 2020

19. Genetic correlations and genome-wide associations of cortical structure in general population samples of 22,824 adults

Author: Hofer, E, Roshchupkin, GV, Adams, HHH, Knol, MJ, Lin, H, Li, S, Zare, H, Ahmad, S, Armstrong, NJ, Satizabal, CL, Bernard, M, Bis, JC, Gillespie, NA, Luciano, M, Mishra, A, Scholz, M, Teumer, A, Xia, R, Jian, X, Mosley, TH, Saba, Y, Pirpamer, L, Seiler, S, Becker, JT, Carmichael, O, Rotter, JI, Psaty, BM, Lopez, OL, Amin, N, van der Lee, SJ, Yang, Q, Himali, JJ, Maillard, P, Beiser, AS, Decarli, C, Karama, S, Lewis, L, Harris, M, Bastin, ME, Deary, IJ, Witte, AV, Beyer, F, Loeffler, M, Mather, KA, Schofield, PR, Thalamuthu, A, Kwok, JB, Wright, MJ, Ames, D, Trollor, J, Jiang, J, Brodaty, H, Wen, W, Vernooij, MW, Hofman, A, Uitterlinden, AG, Niessen, WJ, Wittfeld, K, Bülow, R, Völker, U, Pausova, Z, Pike, GB, Maingault, S, Crivello, F, Tzourio, C, Amouyel, P, Mazoyer, B, Neale, MC, Franz, CE, Lyons, MJ, Panizzon, MS, Andreassen, OA, Dale, AM, Logue, M, Grasby, KL, Jahanshad, N, Painter, JN, Colodro-Conde, L, Bralten, J, Hibar, DP, Lind, PA, Pizzagalli, F, Stein, JL, Thompson, PM, Medland, SE, Sachdev, PS, Kremen, WS, Wardlaw, JM, Villringer, A, van Duijn, CM, Grabe, HJ, Longstreth, WT, Fornage, M, Paus, T, Debette, S, Ikram, MA, Schmidt, H, Schmidt, R, Seshadri, S, Ching, CRK, Hofer, E, Roshchupkin, GV, Adams, HHH, Knol, MJ, Lin, H, Li, S, Zare, H, Ahmad, S, Armstrong, NJ, Satizabal, CL, Bernard, M, Bis, JC, Gillespie, NA, Luciano, M, Mishra, A, Scholz, M, Teumer, A, Xia, R, Jian, X, Mosley, TH, Saba, Y, Pirpamer, L, Seiler, S, Becker, JT, Carmichael, O, Rotter, JI, Psaty, BM, Lopez, OL, Amin, N, van der Lee, SJ, Yang, Q, Himali, JJ, Maillard, P, Beiser, AS, Decarli, C, Karama, S, Lewis, L, Harris, M, Bastin, ME, Deary, IJ, Witte, AV, Beyer, F, Loeffler, M, Mather, KA, Schofield, PR, Thalamuthu, A, Kwok, JB, Wright, MJ, Ames, D, Trollor, J, Jiang, J, Brodaty, H, Wen, W, Vernooij, MW, Hofman, A, Uitterlinden, AG, Niessen, WJ, Wittfeld, K, Bülow, R, Völker, U, Pausova, Z, Pike, GB, Maingault, S, Crivello, F, Tzourio, C, Amouyel, P, Mazoyer, B, Neale, MC, Franz, CE, Lyons, MJ, Panizzon, MS, Andreassen, OA, Dale, AM, Logue, M, Grasby, KL, Jahanshad, N, Painter, JN, Colodro-Conde, L, Bralten, J, Hibar, DP, Lind, PA, Pizzagalli, F, Stein, JL, Thompson, PM, Medland, SE, Sachdev, PS, Kremen, WS, Wardlaw, JM, Villringer, A, van Duijn, CM, Grabe, HJ, Longstreth, WT, Fornage, M, Paus, T, Debette, S, Ikram, MA, Schmidt, H, Schmidt, R, Seshadri, S, and Ching, CRK
Abstract: Cortical thickness, surface area and volumes vary with age and cognitive function, and in neurological and psychiatric diseases. Here we report heritability, genetic correlations and genome-wide associations of these cortical measures across the whole cortex, and in 34 anatomically predefined regions. Our discovery sample comprises 22,824 individuals from 20 cohorts within the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium and the UK Biobank. We identify genetic heterogeneity between cortical measures and brain regions, and 160 genome-wide significant associations pointing to wnt/β-catenin, TGF-β and sonic hedgehog pathways. There is enrichment for genes involved in anthropometric traits, hindbrain development, vascular and neurodegenerative disease and psychiatric conditions. These data are a rich resource for studies of the biological mechanisms behind cortical development and aging.
Published: 2020

20. Cerebral small vessel disease genomics and its implications across the lifespan

Author: Sargurupremraj, M, Suzuki, H, Jian, X, Sarnowski, C, Evans, TE, Bis, JC, Eiriksdottir, G, Sakaue, S, Terzikhan, N, Habes, M, Zhao, W, Armstrong, NJ, Hofer, E, Yanek, LR, Hagenaars, SP, Kumar, RB, van den Akker, EB, McWhirter, RE, Trompet, S, Mishra, A, Saba, Y, Satizabal, CL, Beaudet, G, Petit, L, Tsuchida, A, Zago, L, Schilling, S, Sigurdsson, S, Gottesman, RF, Lewis, CE, Aggarwal, NT, Lopez, OL, Smith, JA, Valdés Hernández, MC, van der Grond, J, Wright, MJ, Knol, MJ, Dörr, M, Thomson, RJ, Bordes, C, Le Grand, Q, Duperron, MG, Smith, AV, Knopman, DS, Schreiner, PJ, Evans, DA, Rotter, JI, Beiser, AS, Maniega, SM, Beekman, M, Trollor, J, Stott, DJ, Vernooij, MW, Wittfeld, K, Niessen, WJ, Soumaré, A, Boerwinkle, E, Sidney, S, Turner, ST, Davies, G, Thalamuthu, A, Völker, U, van Buchem, MA, Bryan, RN, Dupuis, J, Bastin, ME, Ames, D, Teumer, A, Amouyel, P, Kwok, JB, Bülow, R, Deary, IJ, Schofield, PR, Brodaty, H, Jiang, J, Tabara, Y, Setoh, K, Miyamoto, S, Yoshida, K, Nagata, M, Kamatani, Y, Matsuda, F, Psaty, BM, Bennett, DA, De Jager, PL, Mosley, TH, Sachdev, PS, Schmidt, R, Warren, HR, Evangelou, E, Trégouët, DA, de Andrade, M, Basu, S, Berr, C, Brody, JA, Chasman, DI, Dartigues, JF, Folsom, AR, Germain, M, Sargurupremraj, M, Suzuki, H, Jian, X, Sarnowski, C, Evans, TE, Bis, JC, Eiriksdottir, G, Sakaue, S, Terzikhan, N, Habes, M, Zhao, W, Armstrong, NJ, Hofer, E, Yanek, LR, Hagenaars, SP, Kumar, RB, van den Akker, EB, McWhirter, RE, Trompet, S, Mishra, A, Saba, Y, Satizabal, CL, Beaudet, G, Petit, L, Tsuchida, A, Zago, L, Schilling, S, Sigurdsson, S, Gottesman, RF, Lewis, CE, Aggarwal, NT, Lopez, OL, Smith, JA, Valdés Hernández, MC, van der Grond, J, Wright, MJ, Knol, MJ, Dörr, M, Thomson, RJ, Bordes, C, Le Grand, Q, Duperron, MG, Smith, AV, Knopman, DS, Schreiner, PJ, Evans, DA, Rotter, JI, Beiser, AS, Maniega, SM, Beekman, M, Trollor, J, Stott, DJ, Vernooij, MW, Wittfeld, K, Niessen, WJ, Soumaré, A, Boerwinkle, E, Sidney, S, Turner, ST, Davies, G, Thalamuthu, A, Völker, U, van Buchem, MA, Bryan, RN, Dupuis, J, Bastin, ME, Ames, D, Teumer, A, Amouyel, P, Kwok, JB, Bülow, R, Deary, IJ, Schofield, PR, Brodaty, H, Jiang, J, Tabara, Y, Setoh, K, Miyamoto, S, Yoshida, K, Nagata, M, Kamatani, Y, Matsuda, F, Psaty, BM, Bennett, DA, De Jager, PL, Mosley, TH, Sachdev, PS, Schmidt, R, Warren, HR, Evangelou, E, Trégouët, DA, de Andrade, M, Basu, S, Berr, C, Brody, JA, Chasman, DI, Dartigues, JF, Folsom, AR, and Germain, M
Abstract: White matter hyperintensities (WMH) are the most common brain-imaging feature of cerebral small vessel disease (SVD), hypertension being the main known risk factor. Here, we identify 27 genome-wide loci for WMH-volume in a cohort of 50,970 older individuals, accounting for modification/confounding by hypertension. Aggregated WMH risk variants were associated with altered white matter integrity (p = 2.5×10-7) in brain images from 1,738 young healthy adults, providing insight into the lifetime impact of SVD genetic risk. Mendelian randomization suggested causal association of increasing WMH-volume with stroke, Alzheimer-type dementia, and of increasing blood pressure (BP) with larger WMH-volume, notably also in persons without clinical hypertension. Transcriptome-wide colocalization analyses showed association of WMH-volume with expression of 39 genes, of which four encode known drug targets. Finally, we provide insight into BP-independent biological pathways underlying SVD and suggest potential for genetic stratification of high-risk individuals and for genetically-informed prioritization of drug targets for prevention trials.
Published: 2020

21. Age-Related Changes of Peak Width Skeletonized Mean Diffusivity (PSMD) Across the Adult Lifespan: A Multi-Cohort Study

Author: Beaudet, G, Tsuchida, A, Petit, L, Tzourio, C, Caspers, S, Schreiber, J, Pausova, Z, Patel, Y, Paus, T, Schmidt, R, Pirpamer, L, Sachdev, PS, Brodaty, H, Kochan, N, Trollor, J, Wen, W, Armstrong, NJ, Deary, IJ, Bastin, ME, Wardlaw, JM, Munõz Maniega, S, Witte, AV, Villringer, A, Duering, M, Debette, S, Mazoyer, B, Beaudet, G, Tsuchida, A, Petit, L, Tzourio, C, Caspers, S, Schreiber, J, Pausova, Z, Patel, Y, Paus, T, Schmidt, R, Pirpamer, L, Sachdev, PS, Brodaty, H, Kochan, N, Trollor, J, Wen, W, Armstrong, NJ, Deary, IJ, Bastin, ME, Wardlaw, JM, Munõz Maniega, S, Witte, AV, Villringer, A, Duering, M, Debette, S, and Mazoyer, B
Abstract: Parameters of water diffusion in white matter derived from diffusion-weighted imaging (DWI), such as fractional anisotropy (FA), mean, axial, and radial diffusivity (MD, AD, and RD), and more recently, peak width of skeletonized mean diffusivity (PSMD), have been proposed as potential markers of normal and pathological brain ageing. However, their relative evolution over the entire adult lifespan in healthy individuals remains partly unknown during early and late adulthood, and particularly for the PSMD index. Here, we gathered and analyzed cross-sectional diffusion tensor imaging (DTI) data from 10 population-based cohort studies in order to establish the time course of white matter water diffusion phenotypes from post-adolescence to late adulthood. DTI data were obtained from a total of 20,005 individuals aged 18.1 to 92.6 years and analyzed with the same pipeline for computing skeletonized DTI metrics from DTI maps. For each individual, MD, AD, RD, and FA mean values were computed over their FA volume skeleton, PSMD being calculated as the 90% peak width of the MD values distribution across the FA skeleton. Mean values of each DTI metric were found to strongly vary across cohorts, most likely due to major differences in DWI acquisition protocols as well as pre-processing and DTI model fitting. However, age effects on each DTI metric were found to be highly consistent across cohorts. RD, MD, and AD variations with age exhibited the same U-shape pattern, first slowly decreasing during post-adolescence until the age of 30, 40, and 50 years, respectively, then progressively increasing until late life. FA showed a reverse profile, initially increasing then continuously decreasing, slowly until the 70s, then sharply declining thereafter. By contrast, PSMD constantly increased, first slowly until the 60s, then more sharply. These results demonstrate that, in the general population, age affects PSMD in a manner different from that of other DTI metrics. The constant incre
Published: 2020

22. Variants associated withHHIP expression have sex-differential effects on lung function

Author: Fawcett, KA, Wain, LV, Obeidat, M, Melbourne, C, Shrine, N, Guyatt, AL, John, C, Luan, J, Richmond, A, Moksnes, MR, Granell, R, Weiss, S, Imboden, M, May-Wilson, S, Hysi, P, Boutin, TS, Portas, L, Flexeder, C, Harris, SE, Wang, CA, Lyytikäinen, LP, Palviainen, T, Foong, RE, Keidel, D, Minelli, C, Langenberg, C, Bossé, Y, Van den Berge, M, Sin, DD, Hao, K, Campbell, A, Porteous, D, Padmanabhan, S, Smith, BH, Evans, DM, Ring, S, Langhammer, A, Hveem, K, Willer, C, Ewert, R, Stubbe, B, Pirastu, N, Klaric, L, Joshi, PK, Patasova, K, Massimo, M, Polasek, O, Starr, JM, Karrasch, S, Strauch, K, Meitinger, T, Rudan, I, Rantanen, T, Pietiläinen, K, Kähönen, M, Raitakari, OT, Hall, GL, Sly, Peter, Pennell, CE, Kaprio, J, Lehtimäki, T, Vitart, V, Deary, IJ, Jarvis, D, Wilson, JF, Spector, T, Probst-Hensch, N, Wareham, NJ, Völzke, H, Henderson, J, Strachan, DP, Brumpton, BM, Hayward, C, Hall, IP, Tobin, MD, Fawcett, KA, Wain, LV, Obeidat, M, Melbourne, C, Shrine, N, Guyatt, AL, John, C, Luan, J, Richmond, A, Moksnes, MR, Granell, R, Weiss, S, Imboden, M, May-Wilson, S, Hysi, P, Boutin, TS, Portas, L, Flexeder, C, Harris, SE, Wang, CA, Lyytikäinen, LP, Palviainen, T, Foong, RE, Keidel, D, Minelli, C, Langenberg, C, Bossé, Y, Van den Berge, M, Sin, DD, Hao, K, Campbell, A, Porteous, D, Padmanabhan, S, Smith, BH, Evans, DM, Ring, S, Langhammer, A, Hveem, K, Willer, C, Ewert, R, Stubbe, B, Pirastu, N, Klaric, L, Joshi, PK, Patasova, K, Massimo, M, Polasek, O, Starr, JM, Karrasch, S, Strauch, K, Meitinger, T, Rudan, I, Rantanen, T, Pietiläinen, K, Kähönen, M, Raitakari, OT, Hall, GL, Sly, Peter, Pennell, CE, Kaprio, J, Lehtimäki, T, Vitart, V, Deary, IJ, Jarvis, D, Wilson, JF, Spector, T, Probst-Hensch, N, Wareham, NJ, Völzke, H, Henderson, J, Strachan, DP, Brumpton, BM, Hayward, C, Hall, IP, and Tobin, MD
Abstract: Background: Lung function is highly heritable and differs between the sexes throughout life. However, little is known about sex-differential genetic effects on lung function. We aimed to conduct the first genome-wide genotype-by-sex interaction study on lung function to identify genetic effects that differ between males and females. Methods: We tested for interactions between 7,745,864 variants and sex on spirometry-based measures of lung function in UK Biobank (N=303,612), and sought replication in 75,696 independent individuals from the SpiroMeta consortium. Results: Five independent single-nucleotide polymorphisms (SNPs) showed genome-wide significant (P<5x10 -8) interactions with sex on lung function, and 21 showed suggestive interactions (P<1x10 -6). The strongest signal, from rs7697189 (chr4:145436894) on forced expiratory volume in 1 second (FEV 1) (P=3.15x10 -15), was replicated (P=0.016) in SpiroMeta. The C allele increased FEV 1 more in males (untransformed FEV 1 β=0.028 [SE 0.0022] litres) than females (β=0.009 [SE 0.0014] litres), and this effect was not accounted for by differential effects on height, smoking or pubertal age. rs7697189 resides upstream of the hedgehog-interacting protein ( HHIP) gene and was previously associated with lung function and HHIP lung expression. We found HHIP expression was significantly different between the sexes (P=6.90x10 -6), but we could not detect sex differential effects of rs7697189 on expression. Conclusions: We identified a novel genotype-by-sex interaction at a putative enhancer region upstream of the HHIP gene. Establishing the mechanism by which HHIP SNPs have different effects on lung function in males and females will be important for our understanding of lung health and diseases in both sexes.
Published: 2020

23. 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

24. Genetic comorbidity between major depression and cardio-metabolic traits, stratified by age at onset of major depression

Author: Hagenaars, SP, Coleman, JR, Choi, SW, Gaspar, H, Adams, MJ, Howard, DM, Hodgson, K, Traylor, M, Air, TM, Andlauer, TFM, Arolt, V, Baune, BT, Binder, EB, Blackwood, DHR, Boomsma, D, Campbell, A, Cearns, M, Czamara, D, Dannlowski, U, Domschke, K, de Geus, EJC, Hamilton, SP, Hayward, C, Hickie, IB, Hottenga, JJ, Ising, M, Jones, I, Jones, L, Kutalik, Z, Lucae, S, Martin, NG, Milaneschi, Y, Mueller-Myhsok, B, Owen, MJ, Padmanabhan, S, Penninx, BWJH, Pistis, G, Porteous, DJ, Preisig, M, Ripke, S, Shyn, S, Sullivan, PF, Whitfield, JB, Wray, NR, McIntosh, AM, Deary, IJ, Breen, G, Lewis, CM, Hagenaars, SP, Coleman, JR, Choi, SW, Gaspar, H, Adams, MJ, Howard, DM, Hodgson, K, Traylor, M, Air, TM, Andlauer, TFM, Arolt, V, Baune, BT, Binder, EB, Blackwood, DHR, Boomsma, D, Campbell, A, Cearns, M, Czamara, D, Dannlowski, U, Domschke, K, de Geus, EJC, Hamilton, SP, Hayward, C, Hickie, IB, Hottenga, JJ, Ising, M, Jones, I, Jones, L, Kutalik, Z, Lucae, S, Martin, NG, Milaneschi, Y, Mueller-Myhsok, B, Owen, MJ, Padmanabhan, S, Penninx, BWJH, Pistis, G, Porteous, DJ, Preisig, M, Ripke, S, Shyn, S, Sullivan, PF, Whitfield, JB, Wray, NR, McIntosh, AM, Deary, IJ, Breen, G, and Lewis, CM
Abstract: It is imperative to understand the specific and shared etiologies of major depression and cardio-metabolic disease, as both traits are frequently comorbid and each represents a major burden to society. This study examined whether there is a genetic association between major depression and cardio-metabolic traits and if this association is stratified by age at onset for major depression. Polygenic risk scores analysis and linkage disequilibrium score regression was performed to examine whether differences in shared genetic etiology exist between depression case control status (N cases = 40,940, N controls = 67,532), earlier (N = 15,844), and later onset depression (N = 15,800) with body mass index, coronary artery disease, stroke, and type 2 diabetes in 11 data sets from the Psychiatric Genomics Consortium, Generation Scotland, and UK Biobank. All cardio-metabolic polygenic risk scores were associated with depression status. Significant genetic correlations were found between depression and body mass index, coronary artery disease, and type 2 diabetes. Higher polygenic risk for body mass index, coronary artery disease, and type 2 diabetes was associated with both early and later onset depression, while higher polygenic risk for stroke was associated with later onset depression only. Significant genetic correlations were found between body mass index and later onset depression, and between coronary artery disease and both early and late onset depression. The phenotypic associations between major depression and cardio-metabolic traits may partly reflect their overlapping genetic etiology irrespective of the age depression first presents.
Published: 2020

25. The genetic architecture of the human cerebral cortex

Author: Grasby, KL, Jahanshad, N, Painter, JN, Colodro-Conde, L, Bralten, J, Hibar, DP, Lind, PA, Pizzagalli, F, Ching, CRK, McMahon, MAB, Shatokhina, N, Zsembik, LCP, Thomopoulos, SI, Zhu, AH, Strike, LT, Agartz, I, Alhusaini, S, Almeida, MAA, Alnaes, D, Amlien, IK, Andersson, M, Ard, T, Armstrong, NJ, Ashley-Koch, A, Atkins, JR, Bernard, M, Brouwer, RM, Buimer, EEL, Bulow, R, Burger, C, Cannon, DM, Chakravarty, M, Chen, Q, Cheung, JW, Couvy-Duchesne, B, Dale, AM, Dalvie, S, de Araujo, TK, de Zubicaray, GI, de Zwarte, SMC, den Braber, A, Nhat, TD, Dohm, K, Ehrlich, S, Engelbrecht, H-R, Erk, S, Fan, CC, Fedko, IO, Foley, SF, Ford, JM, Fukunaga, M, Garrett, ME, Ge, T, Giddaluru, S, Goldman, AL, Green, MJ, Groenewold, NA, Grotegerd, D, Gurholt, TP, Gutman, BA, Hansell, NK, Harris, MA, Harrison, MB, Haswell, CC, Hauser, M, Herms, S, Heslenfeld, DJ, Ho, NF, Hoehn, D, Hoffmann, P, Holleran, L, Hoogman, M, Hottenga, J-J, Ikeda, M, Janowitz, D, Jansen, IE, Jia, T, Jockwitz, C, Kanai, R, Karama, S, Kasperaviciute, D, Kaufmann, T, Kelly, S, Kikuchi, M, Klein, M, Knapp, M, Knodt, AR, Kramer, B, Lam, M, Lancaster, TM, Lee, PH, Lett, TA, Lewis, LB, Lopes-Cendes, I, Luciano, M, Macciardi, F, Marquand, AF, Mathias, SR, Melzer, TR, Milaneschi, Y, Mirza-Schreiber, N, Moreira, JCV, Muhleisen, TW, Mueller-Myhsok, B, Najt, P, Nakahara, S, Nho, K, Loohuis, LMO, Orfanos, DP, Pearson, JF, Pitcher, TL, Putz, B, Quide, Y, Ragothaman, A, Rashid, FM, Reay, WR, Redlich, R, Reinbold, CS, Repple, J, Richard, G, Riedel, BC, Risacher, SL, Rocha, CS, Mota, NR, Salminen, L, Saremi, A, Saykin, AJ, Schlag, F, Schmaal, L, Schofield, PR, Secolin, R, Shapland, CY, Shen, L, Shin, J, Shumskaya, E, Sonderby, IE, Sprooten, E, Tansey, KE, Teumer, A, Thalamuthu, A, Tordesillas-Gutierrez, D, Turner, JA, Uhlmann, A, Vallerga, CL, van der Meer, D, van Donkelaar, MMJ, van Eijk, L, van Erp, TGM, van Haren, NEM, van Rooij, D, van Tol, M-J, Veldink, JH, Verhoef, E, Walton, E, Wang, M, Wang, Y, Wardlaw, JM, Wen, W, Westlye, LT, Whelan, CD, Witt, SH, Wittfeld, K, Wolf, C, Wolfers, T, Wu, JQ, Yasuda, CL, Zaremba, D, Zhang, Z, Zwiers, MP, Artiges, E, Assareh, AA, Ayesa-Arriola, R, Belger, A, Brandt, CL, Brown, GG, Cichon, S, Curran, JE, Davies, GE, Degenhardt, F, Dennis, MF, Dietsche, B, Djurovic, S, Doherty, CP, Espiritu, R, Garijo, D, Gil, Y, Gowland, PA, Green, RC, Hausler, AN, Heindel, W, Ho, B-C, Hoffmann, WU, Holsboer, F, Homuth, G, Hosten, N, Jack, CR, Jang, M, Jansen, A, Kimbrel, NA, Kolskar, K, Koops, S, Krug, A, Lim, KO, Luykx, JJ, Mathalon, DH, Mather, KA, Mattay, VS, Matthews, S, Van Son, JM, McEwen, SC, Melle, I, Morris, DW, Mueller, BA, Nauck, M, Nordvik, JE, Noethen, MM, O'Leary, DS, Opel, N, Martinot, M-LP, Pike, GB, Preda, A, Quinlan, EB, Rasser, PE, Ratnakar, V, Reppermund, S, Steen, VM, Tooney, PA, Torres, FR, Veltman, DJ, Voyvodic, JT, Whelan, R, White, T, Yamamori, H, Adams, HHH, Bis, JC, Debette, S, Decarli, C, Fornage, M, Gudnason, V, Hofer, E, Ikram, MA, Launer, L, Longstreth, WT, Lopez, OL, Mazoyer, B, Mosley, TH, Roshchupkin, GV, Satizabal, CL, Schmidt, R, Seshadri, S, Yang, Q, Alvim, MKM, Ames, D, Anderson, TJ, Andreassen, OA, Arias-Vasquez, A, Bastin, ME, Baune, BT, Beckham, JC, Blangero, J, Boomsma, DI, Brodaty, H, Brunner, HG, Buckner, RL, Buitelaar, JK, Bustillo, JR, Cahn, W, Cairns, MJ, Calhoun, V, Carr, VJ, Caseras, X, Caspers, S, Cavalleri, GL, Cendes, F, Corvin, A, Crespo-Facorro, B, Dalrymple-Alford, JC, Dannlowski, U, de Geus, EJC, Deary, IJ, Delanty, N, Depondt, C, Desrivieres, S, Donohoe, G, Espeseth, T, Fernandez, G, Fisher, SE, Flor, H, Forstner, AJ, Francks, C, Franke, B, Glahn, DC, Gollub, RL, Grabe, HJ, Gruber, O, Haberg, AK, Hariri, AR, Hartman, CA, Hashimoto, R, Heinz, A, Henskens, FA, Hillegers, MHJ, Hoekstra, PJ, Holmes, AJ, Hong, LE, Hopkins, WD, Pol, HEH, Jernigan, TL, Jonsson, EG, Kahn, RS, Kennedy, MA, Kircher, TTJ, Kochunov, P, Kwok, JBJ, Le Hellard, S, Loughland, CM, Martin, NG, Martinot, J-L, McDonald, C, McMahon, KL, Meyer-Lindenberg, A, Michie, PT, Morey, RA, Mowry, B, Nyberg, L, Oosterlaan, J, Ophoff, RA, Pantelis, C, Paus, T, Pausova, Z, Penninx, BWJH, Polderman, TJC, Posthuma, D, Rietschel, M, Roffman, JL, Rowland, LM, Sachdev, PS, Samann, PG, Schall, U, Schumann, G, Scott, RJ, Sim, K, Sisodiya, SM, Smoller, JW, Sommer, IE, St Pourcain, B, Stein, DJ, Toga, AW, Trollor, JN, Van der Wee, NJA, van't Ent, D, Volzke, H, Walter, H, Weber, B, Weinberger, DR, Wright, MJ, Zhou, J, Stein, JL, Thompson, PM, Medland, SE, Grasby, KL, Jahanshad, N, Painter, JN, Colodro-Conde, L, Bralten, J, Hibar, DP, Lind, PA, Pizzagalli, F, Ching, CRK, McMahon, MAB, Shatokhina, N, Zsembik, LCP, Thomopoulos, SI, Zhu, AH, Strike, LT, Agartz, I, Alhusaini, S, Almeida, MAA, Alnaes, D, Amlien, IK, Andersson, M, Ard, T, Armstrong, NJ, Ashley-Koch, A, Atkins, JR, Bernard, M, Brouwer, RM, Buimer, EEL, Bulow, R, Burger, C, Cannon, DM, Chakravarty, M, Chen, Q, Cheung, JW, Couvy-Duchesne, B, Dale, AM, Dalvie, S, de Araujo, TK, de Zubicaray, GI, de Zwarte, SMC, den Braber, A, Nhat, TD, Dohm, K, Ehrlich, S, Engelbrecht, H-R, Erk, S, Fan, CC, Fedko, IO, Foley, SF, Ford, JM, Fukunaga, M, Garrett, ME, Ge, T, Giddaluru, S, Goldman, AL, Green, MJ, Groenewold, NA, Grotegerd, D, Gurholt, TP, Gutman, BA, Hansell, NK, Harris, MA, Harrison, MB, Haswell, CC, Hauser, M, Herms, S, Heslenfeld, DJ, Ho, NF, Hoehn, D, Hoffmann, P, Holleran, L, Hoogman, M, Hottenga, J-J, Ikeda, M, Janowitz, D, Jansen, IE, Jia, T, Jockwitz, C, Kanai, R, Karama, S, Kasperaviciute, D, Kaufmann, T, Kelly, S, Kikuchi, M, Klein, M, Knapp, M, Knodt, AR, Kramer, B, Lam, M, Lancaster, TM, Lee, PH, Lett, TA, Lewis, LB, Lopes-Cendes, I, Luciano, M, Macciardi, F, Marquand, AF, Mathias, SR, Melzer, TR, Milaneschi, Y, Mirza-Schreiber, N, Moreira, JCV, Muhleisen, TW, Mueller-Myhsok, B, Najt, P, Nakahara, S, Nho, K, Loohuis, LMO, Orfanos, DP, Pearson, JF, Pitcher, TL, Putz, B, Quide, Y, Ragothaman, A, Rashid, FM, Reay, WR, Redlich, R, Reinbold, CS, Repple, J, Richard, G, Riedel, BC, Risacher, SL, Rocha, CS, Mota, NR, Salminen, L, Saremi, A, Saykin, AJ, Schlag, F, Schmaal, L, Schofield, PR, Secolin, R, Shapland, CY, Shen, L, Shin, J, Shumskaya, E, Sonderby, IE, Sprooten, E, Tansey, KE, Teumer, A, Thalamuthu, A, Tordesillas-Gutierrez, D, Turner, JA, Uhlmann, A, Vallerga, CL, van der Meer, D, van Donkelaar, MMJ, van Eijk, L, van Erp, TGM, van Haren, NEM, van Rooij, D, van Tol, M-J, Veldink, JH, Verhoef, E, Walton, E, Wang, M, Wang, Y, Wardlaw, JM, Wen, W, Westlye, LT, Whelan, CD, Witt, SH, Wittfeld, K, Wolf, C, Wolfers, T, Wu, JQ, Yasuda, CL, Zaremba, D, Zhang, Z, Zwiers, MP, Artiges, E, Assareh, AA, Ayesa-Arriola, R, Belger, A, Brandt, CL, Brown, GG, Cichon, S, Curran, JE, Davies, GE, Degenhardt, F, Dennis, MF, Dietsche, B, Djurovic, S, Doherty, CP, Espiritu, R, Garijo, D, Gil, Y, Gowland, PA, Green, RC, Hausler, AN, Heindel, W, Ho, B-C, Hoffmann, WU, Holsboer, F, Homuth, G, Hosten, N, Jack, CR, Jang, M, Jansen, A, Kimbrel, NA, Kolskar, K, Koops, S, Krug, A, Lim, KO, Luykx, JJ, Mathalon, DH, Mather, KA, Mattay, VS, Matthews, S, Van Son, JM, McEwen, SC, Melle, I, Morris, DW, Mueller, BA, Nauck, M, Nordvik, JE, Noethen, MM, O'Leary, DS, Opel, N, Martinot, M-LP, Pike, GB, Preda, A, Quinlan, EB, Rasser, PE, Ratnakar, V, Reppermund, S, Steen, VM, Tooney, PA, Torres, FR, Veltman, DJ, Voyvodic, JT, Whelan, R, White, T, Yamamori, H, Adams, HHH, Bis, JC, Debette, S, Decarli, C, Fornage, M, Gudnason, V, Hofer, E, Ikram, MA, Launer, L, Longstreth, WT, Lopez, OL, Mazoyer, B, Mosley, TH, Roshchupkin, GV, Satizabal, CL, Schmidt, R, Seshadri, S, Yang, Q, Alvim, MKM, Ames, D, Anderson, TJ, Andreassen, OA, Arias-Vasquez, A, Bastin, ME, Baune, BT, Beckham, JC, Blangero, J, Boomsma, DI, Brodaty, H, Brunner, HG, Buckner, RL, Buitelaar, JK, Bustillo, JR, Cahn, W, Cairns, MJ, Calhoun, V, Carr, VJ, Caseras, X, Caspers, S, Cavalleri, GL, Cendes, F, Corvin, A, Crespo-Facorro, B, Dalrymple-Alford, JC, Dannlowski, U, de Geus, EJC, Deary, IJ, Delanty, N, Depondt, C, Desrivieres, S, Donohoe, G, Espeseth, T, Fernandez, G, Fisher, SE, Flor, H, Forstner, AJ, Francks, C, Franke, B, Glahn, DC, Gollub, RL, Grabe, HJ, Gruber, O, Haberg, AK, Hariri, AR, Hartman, CA, Hashimoto, R, Heinz, A, Henskens, FA, Hillegers, MHJ, Hoekstra, PJ, Holmes, AJ, Hong, LE, Hopkins, WD, Pol, HEH, Jernigan, TL, Jonsson, EG, Kahn, RS, Kennedy, MA, Kircher, TTJ, Kochunov, P, Kwok, JBJ, Le Hellard, S, Loughland, CM, Martin, NG, Martinot, J-L, McDonald, C, McMahon, KL, Meyer-Lindenberg, A, Michie, PT, Morey, RA, Mowry, B, Nyberg, L, Oosterlaan, J, Ophoff, RA, Pantelis, C, Paus, T, Pausova, Z, Penninx, BWJH, Polderman, TJC, Posthuma, D, Rietschel, M, Roffman, JL, Rowland, LM, Sachdev, PS, Samann, PG, Schall, U, Schumann, G, Scott, RJ, Sim, K, Sisodiya, SM, Smoller, JW, Sommer, IE, St Pourcain, B, Stein, DJ, Toga, AW, Trollor, JN, Van der Wee, NJA, van't Ent, D, Volzke, H, Walter, H, Weber, B, Weinberger, DR, Wright, MJ, Zhou, J, Stein, JL, Thompson, PM, and Medland, SE
Abstract: The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder.
Published: 2020

26. Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals

Author: Surendran, P, Feofanova, E, Lahrouchi, N, Ntalla, I, Karthikeyan, S, Cook, J, Chen, L, Mifsud, B, Yao, C, Kraja, AT, Cartwright, JH, Hellwege, JN, Giri, A, Tragante, V, Thorleifsson, G, Liu, DJ, Prins, BP, Stewart, ID, Cabrera, CP, Eales, JM, Akbarov, A, Auer, PL, Bielak, LF, Bis, JC, Braithwaite, VS, Brody, JA, Daw, EW, Warren, HR, Drenos, F, Nielsen, SF, Faul, JD, Fauman, EB, Fava, C, Ferreira, T, Foley, CN, Franceschini, N, Gao, H, Giannakopoulou, O, Giulianini, F, Gudbjartsson, DF, Guo, X, Harris, SE, Havulinna, AS, Helgadottir, A, Huffman, JE, Hwang, S-J, Kanoni, S, Kontto, J, Larson, MG, Li-Gao, R, Lindstrom, J, Lotta, LA, Lu, Y, Luan, J, Mahajan, A, Malerba, G, Masca, NGD, Mei, H, Menni, C, Mook-Kanamori, DO, Mosen-Ansorena, D, Muller-Nurasyid, M, Pare, G, Paul, DS, Perola, M, Poveda, A, Rauramaa, R, Richard, M, Richardson, TG, Sepulveda, N, Sim, X, Smith, A, Smith, JA, Staley, JR, Stanakova, A, Sulem, P, Theriault, S, Thorsteinsdottir, U, Trompet, S, Varga, TV, Edwards, DRV, Veronesi, G, Weiss, S, Willems, SM, Yao, J, Young, R, Yu, B, Zhang, W, Zhao, J-H, Zhao, W, Evangelou, E, Aeschbacher, S, Asllanaj, E, Blankenberg, S, Bonnycastle, LL, Bork-Jensen, J, Brandslund, I, Braund, PS, Burgess, S, Cho, K, Christensen, C, Connell, J, de Mutsert, R, Dominiczak, AF, Dorr, M, Eiriksdottir, G, Farmaki, A-E, Gaziano, JM, Grarup, N, Grove, ML, Hallmans, G, Hansen, T, Have, CT, Heiss, G, Jorgensen, ME, Jousilahti, P, Kajantie, E, Kamat, M, Karajamaki, A, Karpe, F, Koistinen, HA, Kovesdy, CP, Kuulasmaa, K, Laatikainen, T, Lannfelt, L, Lee, I-T, Lee, W-J, Linneberg, A, Martin, LW, Moitry, M, Nadkarni, G, Neville, MJ, Palmer, CNA, Papanicolaou, GJ, Pedersen, O, Peters, J, Poulter, N, Rasheed, A, Rasmussen, KL, Rayner, NW, Magi, R, Renstrom, F, Rettig, R, Rossouw, J, Schreiner, PJ, Sever, PS, Sigurdsson, EL, Skaaby, T, Sun, Y, Sundstrom, J, Thorgeirsson, G, Esko, T, Trabetti, E, Tsao, PS, Tuomi, T, Turner, ST, Tzoulaki, I, Vaartjes, I, Vergnaud, A-C, Willer, CJ, Wilson, PWF, Witte, DR, Yonova-Doing, E, Zhang, H, Aliya, N, Almgren, P, Amouyel, P, Asselbergs, FW, Barnes, MR, Blakemore, A, Boehnke, M, Bots, ML, Bottinger, EP, Buring, JE, Chambers, JC, Chen, Y-DI, Chowdhury, R, Conen, D, Correa, A, Smith, GD, de Boer, RA, Deary, IJ, Dedoussis, G, Deloukas, P, Di Angelantonio, E, Elliott, P, Felix, SB, Ferrieres, J, Ford, I, Fornage, M, Franks, PW, Franks, S, Frossard, P, Gambaro, G, Gaunt, TR, Groop, L, Gudnason, V, Harris, TB, Hayward, C, Hennig, BJ, Herzig, K-H, Ingelsson, E, Tuomilehto, J, Jarvelin, M-R, Jukema, JW, Kardia, SLR, Kee, F, Kooner, JS, Kooperberg, C, Launer, LJ, Lind, L, Loos, RJF, Majumder, AAS, Laakso, M, McCarthy, M, Melander, O, Mohlke, KL, Murray, AD, Nordestgaard, BG, Orho-Melander, M, Packard, CJ, Padmanabhan, S, Palmas, W, Polasek, O, Porteous, DJ, Prentice, AM, Province, MA, Relton, CL, Rice, K, Ridker, PM, Rolandsson, O, Rosendaal, FR, Rotter, J, Rudan, I, Salomaa, V, Samani, NJ, Sattar, N, Sheu, WH-H, Smith, BH, Soranzo, N, Spector, TD, Starr, JM, Sebert, S, Taylor, KD, Lakka, TA, Timpson, NJ, Tobin, MD, van der Harst, P, van der Meer, P, Ramachandran, VS, Verweij, N, Virtamo, J, Volker, U, Weir, DR, Zeggini, E, Charchar, FJ, Wareham, NJ, Langenberg, C, Tomaszewski, M, Butterworth, AS, Caulfield, MJ, Danesh, J, Edwards, TL, Holm, H, Hung, AM, Lindgren, CM, Liu, C, Manning, AK, Morris, AP, Morrison, AC, O'Donnell, CJ, Psaty, BM, Saleheen, D, Stefansson, K, Boerwinkle, E, Chasman, D, Levy, D, Newton-Cheh, C, Munroe, PB, Howson, JMM, Surendran, P, Feofanova, E, Lahrouchi, N, Ntalla, I, Karthikeyan, S, Cook, J, Chen, L, Mifsud, B, Yao, C, Kraja, AT, Cartwright, JH, Hellwege, JN, Giri, A, Tragante, V, Thorleifsson, G, Liu, DJ, Prins, BP, Stewart, ID, Cabrera, CP, Eales, JM, Akbarov, A, Auer, PL, Bielak, LF, Bis, JC, Braithwaite, VS, Brody, JA, Daw, EW, Warren, HR, Drenos, F, Nielsen, SF, Faul, JD, Fauman, EB, Fava, C, Ferreira, T, Foley, CN, Franceschini, N, Gao, H, Giannakopoulou, O, Giulianini, F, Gudbjartsson, DF, Guo, X, Harris, SE, Havulinna, AS, Helgadottir, A, Huffman, JE, Hwang, S-J, Kanoni, S, Kontto, J, Larson, MG, Li-Gao, R, Lindstrom, J, Lotta, LA, Lu, Y, Luan, J, Mahajan, A, Malerba, G, Masca, NGD, Mei, H, Menni, C, Mook-Kanamori, DO, Mosen-Ansorena, D, Muller-Nurasyid, M, Pare, G, Paul, DS, Perola, M, Poveda, A, Rauramaa, R, Richard, M, Richardson, TG, Sepulveda, N, Sim, X, Smith, A, Smith, JA, Staley, JR, Stanakova, A, Sulem, P, Theriault, S, Thorsteinsdottir, U, Trompet, S, Varga, TV, Edwards, DRV, Veronesi, G, Weiss, S, Willems, SM, Yao, J, Young, R, Yu, B, Zhang, W, Zhao, J-H, Zhao, W, Evangelou, E, Aeschbacher, S, Asllanaj, E, Blankenberg, S, Bonnycastle, LL, Bork-Jensen, J, Brandslund, I, Braund, PS, Burgess, S, Cho, K, Christensen, C, Connell, J, de Mutsert, R, Dominiczak, AF, Dorr, M, Eiriksdottir, G, Farmaki, A-E, Gaziano, JM, Grarup, N, Grove, ML, Hallmans, G, Hansen, T, Have, CT, Heiss, G, Jorgensen, ME, Jousilahti, P, Kajantie, E, Kamat, M, Karajamaki, A, Karpe, F, Koistinen, HA, Kovesdy, CP, Kuulasmaa, K, Laatikainen, T, Lannfelt, L, Lee, I-T, Lee, W-J, Linneberg, A, Martin, LW, Moitry, M, Nadkarni, G, Neville, MJ, Palmer, CNA, Papanicolaou, GJ, Pedersen, O, Peters, J, Poulter, N, Rasheed, A, Rasmussen, KL, Rayner, NW, Magi, R, Renstrom, F, Rettig, R, Rossouw, J, Schreiner, PJ, Sever, PS, Sigurdsson, EL, Skaaby, T, Sun, Y, Sundstrom, J, Thorgeirsson, G, Esko, T, Trabetti, E, Tsao, PS, Tuomi, T, Turner, ST, Tzoulaki, I, Vaartjes, I, Vergnaud, A-C, Willer, CJ, Wilson, PWF, Witte, DR, Yonova-Doing, E, Zhang, H, Aliya, N, Almgren, P, Amouyel, P, Asselbergs, FW, Barnes, MR, Blakemore, A, Boehnke, M, Bots, ML, Bottinger, EP, Buring, JE, Chambers, JC, Chen, Y-DI, Chowdhury, R, Conen, D, Correa, A, Smith, GD, de Boer, RA, Deary, IJ, Dedoussis, G, Deloukas, P, Di Angelantonio, E, Elliott, P, Felix, SB, Ferrieres, J, Ford, I, Fornage, M, Franks, PW, Franks, S, Frossard, P, Gambaro, G, Gaunt, TR, Groop, L, Gudnason, V, Harris, TB, Hayward, C, Hennig, BJ, Herzig, K-H, Ingelsson, E, Tuomilehto, J, Jarvelin, M-R, Jukema, JW, Kardia, SLR, Kee, F, Kooner, JS, Kooperberg, C, Launer, LJ, Lind, L, Loos, RJF, Majumder, AAS, Laakso, M, McCarthy, M, Melander, O, Mohlke, KL, Murray, AD, Nordestgaard, BG, Orho-Melander, M, Packard, CJ, Padmanabhan, S, Palmas, W, Polasek, O, Porteous, DJ, Prentice, AM, Province, MA, Relton, CL, Rice, K, Ridker, PM, Rolandsson, O, Rosendaal, FR, Rotter, J, Rudan, I, Salomaa, V, Samani, NJ, Sattar, N, Sheu, WH-H, Smith, BH, Soranzo, N, Spector, TD, Starr, JM, Sebert, S, Taylor, KD, Lakka, TA, Timpson, NJ, Tobin, MD, van der Harst, P, van der Meer, P, Ramachandran, VS, Verweij, N, Virtamo, J, Volker, U, Weir, DR, Zeggini, E, Charchar, FJ, Wareham, NJ, Langenberg, C, Tomaszewski, M, Butterworth, AS, Caulfield, MJ, Danesh, J, Edwards, TL, Holm, H, Hung, AM, Lindgren, CM, Liu, C, Manning, AK, Morris, AP, Morrison, AC, O'Donnell, CJ, Psaty, BM, Saleheen, D, Stefansson, K, Boerwinkle, E, Chasman, D, Levy, D, Newton-Cheh, C, Munroe, PB, and Howson, JMM
Abstract: Genetic studies of blood pressure (BP) to date have mainly analyzed common variants (minor allele frequency > 0.05). In a meta-analysis of up to ~1.3 million participants, we discovered 106 new BP-associated genomic regions and 87 rare (minor allele frequency ≤ 0.01) variant BP associations (P < 5 × 10-8), of which 32 were in new BP-associated loci and 55 were independent BP-associated single-nucleotide variants within known BP-associated regions. Average effects of rare variants (44% coding) were ~8 times larger than common variant effects and indicate potential candidate causal genes at new and known loci (for example, GATA5 and PLCB3). BP-associated variants (including rare and common) were enriched in regions of active chromatin in fetal tissues, potentially linking fetal development with BP regulation in later life. Multivariable Mendelian randomization suggested possible inverse effects of elevated systolic and diastolic BP on large artery stroke. Our study demonstrates the utility of rare-variant analyses for identifying candidate genes and the results highlight potential therapeutic targets.
Published: 2020

27. 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

28. Association of common genetic variants with brain microbleeds: A genome-wide association study

Author: Knol, Maria, Lu, Difei, Traylor, M, Adams, Hieab, Romero, JR, Smith, AV, Fornage, M, Hofer, E, Liu, Jun, Hostettler, IC, Luciano, M, Trompet, S, Giese, A K, Hilal, S, van den Akker, EB, Vojinovic, Dina, Li, S, Sigurdsson, S, van der Lee, Sven, Jack, CR, Wilson, D, Yilmaz, Pinar, Satizabal, CL, Liewald, DCM, van der Grond, J, Chen, C, Saba, Y, van der Lugt, Aad, Bastin, ME, Windham, BG, Cheng, CY (Ching-Yu), Pirpamer, L, Kantarci, K, Himali, JJ, Yang, Q, Morris, Z, Beiser, AS, Tozer, DJ, Vernooij, Meike, Amin, Najaf, Beekman, M, Koh, JY, Stott, DJM, Houlden, H, Schmidt, R, Gottesman, RF, MacKinnon, AD, DeCarli, C, Gudnason, V, Deary, IJ, Duijn, Cornelia, Slagboom, PE, Wong, TY, Rost, NS, Jukema, JW, Mosley, TH, Jr, Werring, DJ, Schmidt, H, Wardlaw, JM, Ikram, Arfan, Seshadri, S, Launer, LJ, Markus, HS, Knol, Maria, Lu, Difei, Traylor, M, Adams, Hieab, Romero, JR, Smith, AV, Fornage, M, Hofer, E, Liu, Jun, Hostettler, IC, Luciano, M, Trompet, S, Giese, A K, Hilal, S, van den Akker, EB, Vojinovic, Dina, Li, S, Sigurdsson, S, van der Lee, Sven, Jack, CR, Wilson, D, Yilmaz, Pinar, Satizabal, CL, Liewald, DCM, van der Grond, J, Chen, C, Saba, Y, van der Lugt, Aad, Bastin, ME, Windham, BG, Cheng, CY (Ching-Yu), Pirpamer, L, Kantarci, K, Himali, JJ, Yang, Q, Morris, Z, Beiser, AS, Tozer, DJ, Vernooij, Meike, Amin, Najaf, Beekman, M, Koh, JY, Stott, DJM, Houlden, H, Schmidt, R, Gottesman, RF, MacKinnon, AD, DeCarli, C, Gudnason, V, Deary, IJ, Duijn, Cornelia, Slagboom, PE, Wong, TY, Rost, NS, Jukema, JW, Mosley, TH, Jr, Werring, DJ, Schmidt, H, Wardlaw, JM, Ikram, Arfan, Seshadri, S, Launer, LJ, and Markus, HS
Published: 2020

29. Meta-analysis of epigenome-wide association studies of cognitive abilities

Author: Marioni, RE, McRae, AF, Bressler, J, Colicino, E, Hannon, E, Li, S, Prada, D, Smith, JA, Trevisi, L, Tsai, P-C, Vojinovic, D, Simino, J, Levy, D, Liu, C, Mendelson, M, Satizabal, CL, Yang, Q, Jhun, MA, Kardia, SLR, Zhao, W, Bandinelli, S, Ferrucci, L, Hernandez, DG, Singleton, AB, Harris, SE, Starr, JM, Kiel, DP, McLean, RR, Just, AC, Schwartz, J, Spiro, A, Vokonas, P, Amin, N, Ikram, MA, Uitterlinden, AG, Van Meurs, JBJ, Spector, TD, Steves, C, Baccarelli, AA, Bell, JT, Van Duijn, CM, Fornage, M, Hsu, Y-H, Mill, J, Mosley, TH, Seshadri, S, Deary, IJ, Epidemiology, Gastroenterology & Hepatology, Neurology, Radiology & Nuclear Medicine, and Internal Medicine
Subjects: Adult, Aged, 80 and over, Male, Genomics, DNA Methylation, Middle Aged, Epigenesis, Genetic, Cohort Studies, Cognition, Humans, CpG Islands, Female, Immediate Communication, Aged, Genome-Wide Association Study
Abstract: Cognitive functions are important correlates of health outcomes across the life-course. Individual differences in cognitive functions are partly heritable. Epigenetic modifications, such as DNA methylation, are susceptible to both genetic and environmental factors and may provide insights into individual differences in cognitive functions. Epigenome-wide meta-analyses for blood-based DNA methylation levels at ~420,000 CpG sites were performed for seven measures of cognitive functioning using data from 11 cohorts. CpGs that passed a Bonferroni correction, adjusting for the number of CpGs and cognitive tests, were assessed for: longitudinal change; being under genetic control (methylation QTLs); and associations with brain health (structural MRI), brain methylation and Alzheimer's disease pathology. Across the seven measures of cognitive functioning (meta-analysis n range: 2557-6809), there were epigenome-wide significant (P
Published: 2018
Full Text: View/download PDF

30. Cerebral Small Vessel Disease Burden and Longitudinal Cognitive Decline from age 73 to 82: the Lothian Birth Cohort 1936

Author: Hamilton, OKL, primary, Cox, SR, additional, Okely, JA, additional, Conte, F, additional, Ballerini, L, additional, Bastin, ME, additional, Corley, J, additional, Taylor, AM, additional, Page, D, additional, Gow, AJ, additional, Muñoz Maniega, S, additional, Redmond, P, additional, Valdés-Hernández, M del C, additional, Wardlaw, JM, additional, and Deary, IJ, additional
Published: 2021
Full Text: View/download PDF

31. Associations between total MRI-visible small vessel disease burden and domain-specific cognitive abilities in a community-dwelling older-age cohort

Author: Hamilton, OKL, primary, Cox, SR, additional, Ballerini, L, additional, Bastin, ME, additional, Corley, J, additional, Gow, AJ, additional, Muñoz Maniega, S, additional, Redmond, P, additional, M del C, Valdés-Hernández, additional, Wardlaw, JM, additional, and Deary, IJ, additional
Published: 2021
Full Text: View/download PDF

32. Seven-year follow-up of blood pressure in the Healthy Old People in Edinburgh (HOPE) cohort

Author: Starr, JM, Inch, S, Cross, S, and Deary, IJ
Published: 2000
Full Text: View/download PDF

33. Commentary: Birthweight and childhood cognition: the use of twin studies

Author: Shenkin, SD, Deary, IJ, and Batty, GD
Published: 2011
Full Text: View/download PDF

34. Three major dimensions of human brain cortical ageing in relation to cognitive decline across the 8thdecade of life

Author: Cox, SR, primary, Harris, MA, additional, Ritchie, SJ, additional, Buchanan, CR, additional, Valdés Hernández, MC, additional, Corley, J, additional, Taylor, AM, additional, Madole, JW, additional, Harris, SE, additional, Whalley, HC, additional, McIntosh, AM, additional, Russ, TC, additional, Bastin, ME, additional, Wardlaw, JM, additional, Deary, IJ, additional, and Tucker-Drob, EM, additional
Published: 2020
Full Text: View/download PDF

35. Brain age predicts mortality

Author: Cole, JH, Ritchie, SJ, Bastin, ME, Valdes Hernandez, MC, Munoz Maniega, S, Royle, N, Corely, J, Pattie, A, Harris, SE, Zhang, Q, Wray, N, Redmond, P, Marioni, RE, Starr, JM, Cox, SR, Wardlaw, JM, Sharp, DJ, Deary, IJ, Commission of the European Communities, and National Institute for Health Research
Subjects: Psychiatry, Adult, Aged, 80 and over, Epigenomics, Male, Aging, Brain, Neuroimaging, 11 Medical And Health Sciences, 06 Biological Sciences, Middle Aged, Epigenesis, Genetic, 17 Psychology And Cognitive Sciences, Machine Learning, Cognition, Journal Article, Humans, Original Article, Female, Longitudinal Studies, Biomarkers, Aged
Abstract: Age-associated disease and disability are placing a growing burden on society. However, ageing does not affect people uniformly. Hence, markers of the underlying biological ageing process are needed to help identify people at increased risk of age-associated physical and cognitive impairments and ultimately, death. Here, we present such a biomarker, 'brain-predicted age', derived using structural neuroimaging. Brain-predicted age was calculated using machine-learning analysis, trained on neuroimaging data from a large healthy reference sample (N=2001), then tested in the Lothian Birth Cohort 1936 (N=669), to determine relationships with age-associated functional measures and mortality. Having a brain-predicted age indicative of an older-appearing brain was associated with: weaker grip strength, poorer lung function, slower walking speed, lower fluid intelligence, higher allostatic load and increased mortality risk. Furthermore, while combining brain-predicted age with grey matter and cerebrospinal fluid volumes (themselves strong predictors) not did improve mortality risk prediction, the combination of brain-predicted age and DNA-methylation-predicted age did. This indicates that neuroimaging and epigenetics measures of ageing can provide complementary data regarding health outcomes. Our study introduces a clinically-relevant neuroimaging ageing biomarker and demonstrates that combining distinct measurements of biological ageing further helps to determine risk of age-related deterioration and death.Molecular Psychiatry advance online publication, 25 April 2017; doi:10.1038/mp.2017.62.
Published: 2017
Full Text: View/download PDF

36. Blood pressure and cognitive decline in healthy old people

Author: Starr, JM, Deary, IJ, Inch, S, Cross, S, and MacLennan, WJ
Published: 1997
Full Text: View/download PDF

37. Cross-sectional associations between personality traits and device-based measures of step count and sedentary behaviour in older age: the Lothian Birth Cohort 1936

Author: Cukic, I, Gale, C R, Chastin, SFM, Dall, PM, Dontje, Manon, Skelton, DA, Deary, IJ, Cox, S, Coulter, E, Der, G, Fitzsimons, C, Gill, J, Granat, M, Gray, C, Greig, C, Hindle, E, Laird, K, Mead, G, Mutrie, N, Palmer, V, Radakovic, R, Sattar, N, Shaw, R, Starr, J, Stewart, S, Wyke, S, and Public Health
Subjects: Male, Aging, Older age, lcsh:Geriatrics, Cohort Studies, 0302 clinical medicine, Medicine and Health Sciences, SITTING TIME, Medicine, 030212 general & internal medicine, Big Five personality traits, Personality traits, media_common, RISK, CARDIOVASCULAR-DISEASE, Female, Birth cohort, Research Article, Personality, media_common.quotation_subject, Physical activity, Fitness Trackers, Health outcomes, Age and sex, 03 medical and health sciences, Step count, Humans, Device-based measures, activPAL, Exercise, METAANALYSIS, Aged, Sedentary time, business.industry, MORTALITY, 030229 sport sciences, ADULTS, Sedentary behaviour, United Kingdom, lcsh:RC952-954.6, Cross-Sectional Studies, PHYSICAL-ACTIVITY, Scotland, Self Report, Geriatrics and Gerontology, Sedentary Behavior, business, Demography
Abstract: Background While the associations between personality traits and self-reported physical activity are well replicated, few studies have examined the associations between personality and device-based measures of both physical activity and sedentary behaviour. Low levels of physical activity and high levels of sedentary behaviour are known risk factors for poorer health outcomes in older age. Methods We used device-based measures of physical activity and sedentary behaviour recorded over 7 days in 271 79-year-old participants of the Lothian Birth Cohort 1936. Linear regression models were used to assess whether personality traits were cross-sectionally associated with step count, sedentary time, and the number of sit-to-stand transitions. Personality traits were entered one at a time, and all-together, controlling for age and sex in Model 1 and additionally for BMI and limiting long-term illness in Model 2. Results None of the associations between personality traits and measures of physical activity and sedentary behaviours remained significant after controlling for multiple-comparisons using the False Discovery Rate test (all ps > .07). Conclusions We found no evidence that personality traits are associated with device-based measures of physical activity or sedentary behaviour in older age. More studies are needed to replicate and examine the nature of these relationships.
Published: 2019
Full Text: View/download PDF

38. Submissiveness and protection from coronary heart disease in the general population: Edinburgh Artery Study

Author: Whiteman, MC, Deary, IJ, Lee, AJ, and Fowkes, Fgr
Published: 1997

39. Corticosteroids and Regional Variations in Thickness of the Human Cerebral Cortex across the Lifespan

Author: Parker, N, Vidal-Pineiro, D, French, L, Shin, J, Adams, HHH, Brodaty, H, Cox, SR, Deary, IJ, Fjell, AM, Frenzel, S, Grabe, H, Hosten, N, Ikram, MA, Jiang, J, Knol, MJ, Mazoyer, B, Mishra, A, Sachdev, PS, Salum, G, Satizabal, CL, Schmidt, H, Schmidt, R, Seshadri, S, Schumann, G, Völzke, H, Walhovd, KB, Wen, W, Wittfeld, K, Yang, Q, Debette, S, Pausova, Z, Paus, T, Parker, N, Vidal-Pineiro, D, French, L, Shin, J, Adams, HHH, Brodaty, H, Cox, SR, Deary, IJ, Fjell, AM, Frenzel, S, Grabe, H, Hosten, N, Ikram, MA, Jiang, J, Knol, MJ, Mazoyer, B, Mishra, A, Sachdev, PS, Salum, G, Satizabal, CL, Schmidt, H, Schmidt, R, Seshadri, S, Schumann, G, Völzke, H, Walhovd, KB, Wen, W, Wittfeld, K, Yang, Q, Debette, S, Pausova, Z, and Paus, T
Published: 2019

40. Genetic and lifestyle risk factors for MRI-defined brain infarcts in a population-based setting

Author: Chauhan, G, Adams, HHH, Satizabal, CL, Bis, JC, Teumer, A, Sargurupremraj, M, Hofer, E, Trompet, S, Hilal, S, Smith, AV, Jian, X, Malik, R, Traylor, M, Pulit, SL, Amouyel, P, Mazoyer, B, Zhu, YC, Kaffashian, S, Schilling, S, Beecham, GW, Montine, TJ, Schellenberg, GD, Kjartansson, O, Guðnason, V, Knopman, DS, Griswold, ME, Windham, BG, Gottesman, RF, Mosley, TH, Schmidt, R, Saba, Y, Schmidt, H, Takeuchi, F, Yamaguchi, S, Nabika, T, Kato, N, Rajan, KB, Aggarwal, NT, De Jager, PL, Evans, DA, Psaty, BM, Rotter, JI, Rice, K, Lopez, OL, Liao, J, Chen, C, Cheng, CY, Wong, TY, Ikram, MK, van der Lee, SJ, Amin, N, Chouraki, V, Destefano, AL, Aparicio, HJ, Romero, JR, Maillard, P, Decarli, C, Wardlaw, JM, Del C. Valdés Hernández, M, Luciano, M, Liewald, D, Deary, IJ, Starr, JM, Bastin, ME, Maniega, SM, Slagboom, PE, Beekman, M, Deelen, J, Uh, HW, Lemmens, R, Brodaty, H, Wright, MJ, Ames, D, Boncoraglio, GB, Hopewell, JC, Beecham, AH, Blanton, SH, Wright, CB, Sacco, RL, Wen, W, Thalamuthu, A, Armstrong, NJ, Chong, E, Schofield, PR, Kwok, JB, van der Grond, J, Stott, DJ, Ford, I, Jukema, JW, Vernooij, MW, Hofman, A, Uitterlinden, AG, van der Lugt, A, Wittfeld, K, Grabe, HJ, Hosten, N, von Sarnowski, B, Völker, U, Levi, C, Jimenez-Conde, J, Chauhan, G, Adams, HHH, Satizabal, CL, Bis, JC, Teumer, A, Sargurupremraj, M, Hofer, E, Trompet, S, Hilal, S, Smith, AV, Jian, X, Malik, R, Traylor, M, Pulit, SL, Amouyel, P, Mazoyer, B, Zhu, YC, Kaffashian, S, Schilling, S, Beecham, GW, Montine, TJ, Schellenberg, GD, Kjartansson, O, Guðnason, V, Knopman, DS, Griswold, ME, Windham, BG, Gottesman, RF, Mosley, TH, Schmidt, R, Saba, Y, Schmidt, H, Takeuchi, F, Yamaguchi, S, Nabika, T, Kato, N, Rajan, KB, Aggarwal, NT, De Jager, PL, Evans, DA, Psaty, BM, Rotter, JI, Rice, K, Lopez, OL, Liao, J, Chen, C, Cheng, CY, Wong, TY, Ikram, MK, van der Lee, SJ, Amin, N, Chouraki, V, Destefano, AL, Aparicio, HJ, Romero, JR, Maillard, P, Decarli, C, Wardlaw, JM, Del C. Valdés Hernández, M, Luciano, M, Liewald, D, Deary, IJ, Starr, JM, Bastin, ME, Maniega, SM, Slagboom, PE, Beekman, M, Deelen, J, Uh, HW, Lemmens, R, Brodaty, H, Wright, MJ, Ames, D, Boncoraglio, GB, Hopewell, JC, Beecham, AH, Blanton, SH, Wright, CB, Sacco, RL, Wen, W, Thalamuthu, A, Armstrong, NJ, Chong, E, Schofield, PR, Kwok, JB, van der Grond, J, Stott, DJ, Ford, I, Jukema, JW, Vernooij, MW, Hofman, A, Uitterlinden, AG, van der Lugt, A, Wittfeld, K, Grabe, HJ, Hosten, N, von Sarnowski, B, Völker, U, Levi, C, and Jimenez-Conde, J
Abstract: Objective To explore genetic and lifestyle risk factors of MRI-defined brain infarcts (BI) in large population-based cohorts. Methods We performed meta-analyses of genome-wide association studies (GWAS) and examined associations of vascular risk factors and their genetic risk scores (GRS) with MRI-defined BI and a subset of BI, namely, small subcortical BI (SSBI), in 18 population-based cohorts (n=20,949) from 5 ethnicities (3,726 with BI, 2,021 with SSBI). Top loci were followed up in 7 population-based cohorts (n = 6,862; 1,483 with BI, 630 with SBBI), and we tested associations with related phenotypes including ischemic stroke and pathologically defined BI. Results The mean prevalence was 17.7% for BI and 10.5% for SSBI, steeply rising after age 65. Two loci showed genome-wide significant association with BI: FBN2, p = 1.77 × 10-8; and LINC00539/ZDHHC20, p = 5.82 × 10-9. Both have been associated with blood pressure (BP)-related phenotypes, but did not replicate in the smaller follow-up sample or show associations with related phenotypes. Age- and sex-adjusted associations with BI and SSBI were observed for BP traits (p value for BI, p[BI] = 9.38 × 10-25; p [SSBI] = 5.23 × 10-14 for hypertension), smoking (p[BI]= 4.4 × 10-10; p [SSBI] = 1.2 × 10 -4), diabetes (p[BI] = 1.7 × 10 -8; p [SSBI] = 2.8 × 10 -3), previous cardiovascular disease (p [BI] = 1.0 × 10-18; p [SSBI] = 2.3 × 10-7), stroke (p [BI] = 3.9 × 10-69; p [SSBI] = 3.2 × 10 -24), and MRI-defined white matter hyperintensity burden (p [BI]=1.43 × 10-157; p [SSBI] = 3.16 × 10-106), but not with body mass index or cholesterol. GRS of BP traits were associated with BI and SSBI (p ≤ 0.0022), without indication of directional pleiotropy. Conclusion In this multiethnic GWAS meta-analysis, including over 20,000 population-based participants, we identified genetic risk loci for BI requiring validation once additional large datasets become available. High BP, including genetically determined, was the most significan
Published: 2019

41. 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

42. 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

43. 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

44. Genomic structural equation modelling provides insights into the multivariate genetic architecture of complex traits

Author: Grotzinger, AD, Rhemtulla, M, de Vlaming, R, Ritchie, S J, Mallard, TT, Hill, WD, Ip, HF, Marioni, RE, McIntosh, AM, Deary, IJ, Koellinger, PD, Harden, KP, Nivard, MG, Tucker-Drob, EM, Grotzinger, AD, Rhemtulla, M, de Vlaming, R, Ritchie, S J, Mallard, TT, Hill, WD, Ip, HF, Marioni, RE, McIntosh, AM, Deary, IJ, Koellinger, PD, Harden, KP, Nivard, MG, and Tucker-Drob, EM
Published: 2019

45. Spatial Gradient of Microstructural Changes in Normal-Appearing White Matter in Tracts Affected by White Matter Hyperintensities in Older Age

Author: Maniega, SM, Meijboom, Rozanna, Chappell, FM, Hernandez, MDV, Starr, JM, Bastin, ME, Deary, IJ, Wardlaw, JM, Maniega, SM, Meijboom, Rozanna, Chappell, FM, Hernandez, MDV, Starr, JM, Bastin, ME, Deary, IJ, and Wardlaw, JM
Published: 2019

46. Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity

Author: Kilpelainen, TO, Bentley, AR, Noordam, R, Sung, YJ, Schwander, K, Winkler, TW, Jakupovic, H, Chasman, DI, Manning, A, Ntalla, I, Aschard, H, Brown, MR, de Las Fuentes, L, Franceschini, N, Guo, XQ, Vojinovic, Dina, Aslibekyan, S, Feitosa, MF, Kho, M, Musani, SK, Richard, M, Wang, HM, Wang, Z, Bartz, TM, Bielak, LF, Campbell, A (Archie), Dorajoo, R, Fisher, V, Hartwig, FP, Horimoto, A, Li, CW, Lohman, KK, Marten, J, Sim, XL, Smith, AV, Tajuddin, S M, Alver, M, Amini, M, Boissel, M, Chai, JF, Chen, X, Divers, J, Evangelou, E, Gao, C, Graff, M, Harris, SE, He, MA, Hsu, FC, Jackson, AU, Zhao, JH, Kraja, AT, Kuhnel, B, Laguzzi, F, Lyytikainen, LP, Nolte, IM, Rauramaa, R, Riaz, M, Robino, A, Rueedi, R, Stringham, HM, Takeuchi, F, van der Most, PJ, Varga, TV, Verweij, N, Ware, EB, Wen, WQ, Li, X Y, Yanek, LR, Amin, Najaf, Arnett, DK, Boerwinkle, E, Brumat, M, Cade, B, Canouil, M, Chen, YDI, Concas, MP, Connell, J, de Mutsert, R, de Silva, HJ, de Vries, PS, Demirkan, Ayse, Ding, JZ (Jing Zhong), Eaton, CB, Faul, JD, Friedlander, Y, Gabriel, KP, Ghanbari, Mohsen, Giulianini, F, Gu, CC, Gu, DF, Harris, TB, He, J, Heikkinen, S, Heng, CK, Hunt, SC, Ikram, Arfan, Jonas, JB, Koh, WP, Komulainen, P, Krieger, JE, Kritchevsky, SB, Kutalik, Z, Kuusisto, J, Langefeld, CD, Langenberg, C, Launer, LJ, Leander, K, Lemaitre, RN, Lewis, CE, Liang, JJ, Alizadeh, BZ, Boezen, HM, Franke, L, Navis, G, Rots, M, Swertz, M, Wolffenbuttel, BHR, Wijmenga, C, Liu, JJ, Maagi, R, Manichaikul, A, Meitinger, T, Metspalu, A, Milaneschi, Y, Mohlke, KL, Mosley, TH, Murray, AD, Nalls, MA, Nang, EEK, Nelson, CP, Nona, S, Norris, JM, Nwuba, CV, O'Connell, J, Palmer, ND, Papanicolau, GJ, Pazoki, R, Pedersen, NL, Peters, A, Peyser, PA, Polasek, O, Porteous, DJ, Poveda, A, Raitakari, OT, Rich, SS, Risch, N, Robinson, JG, Rose, LM, Rudan, I, Schreiner, PJ, Scott, RA, Sidney, SS, Sims, M, Smith, JA, Snieder, H, Sofer, T, Starr, JM, Sternfeld, B, Strauch, K, Tang, H, Taylor, KD, Tsai, MY, Tuomilehto, J, Uitterlinden, André, van der Ende, MY, van Heemst, D, Voortman, Trudy, Waldenberger, M, Wennberg, P, Wilson, G, Xiang, YB, Yao, J, Yu, CZ, Yuan, JM, Zhao, W, Zonderman, AB, Becker, DM, Boehnke, M, Bowden, DW, de Faire, U, Deary, IJ, Elliott, P, Esko, T, Freedman, BI, Froguel, P, Gasparini, P, Gieger, C, Kato, N, Laakso, M, Lakka, TA, Lehtimaki, T, Magnusson, PKE, Oldehinkel, AJ, Penninx, B, Samani, NJ, Shu, XO, van der Harst, P, van Vliet-Ostaptchouk, JV, Vollenweider, P, Wagenknecht, LE, Wang, YX, Wareham, NJ, Weir, DR, Wu, TC, Zheng, W, Zhu, XF, Evans, MK, Franks, PW, Gudnason, V, Hayward, C, Horta, BL, Kelly, TN, Liu, YM, North, KE, Pereira, AC, Ridker, PM, Tai, ES, van Dam, RM, Fox, ER, Kardia, SLR, Liu, CT, Mook, Dennis, Province, MA, Redline, S, Duijn, Cornelia, Rotter, JI, Kooperberg, CB, Gauderman, WJ, Psaty, BM, Rice, K, Munroe, PB, Fornage, M, Cupples, LA, Rotimi, CN, Morrison, AC, Rao, DC, Loos, RJF, Kilpelainen, TO, Bentley, AR, Noordam, R, Sung, YJ, Schwander, K, Winkler, TW, Jakupovic, H, Chasman, DI, Manning, A, Ntalla, I, Aschard, H, Brown, MR, de Las Fuentes, L, Franceschini, N, Guo, XQ, Vojinovic, Dina, Aslibekyan, S, Feitosa, MF, Kho, M, Musani, SK, Richard, M, Wang, HM, Wang, Z, Bartz, TM, Bielak, LF, Campbell, A (Archie), Dorajoo, R, Fisher, V, Hartwig, FP, Horimoto, A, Li, CW, Lohman, KK, Marten, J, Sim, XL, Smith, AV, Tajuddin, S M, Alver, M, Amini, M, Boissel, M, Chai, JF, Chen, X, Divers, J, Evangelou, E, Gao, C, Graff, M, Harris, SE, He, MA, Hsu, FC, Jackson, AU, Zhao, JH, Kraja, AT, Kuhnel, B, Laguzzi, F, Lyytikainen, LP, Nolte, IM, Rauramaa, R, Riaz, M, Robino, A, Rueedi, R, Stringham, HM, Takeuchi, F, van der Most, PJ, Varga, TV, Verweij, N, Ware, EB, Wen, WQ, Li, X Y, Yanek, LR, Amin, Najaf, Arnett, DK, Boerwinkle, E, Brumat, M, Cade, B, Canouil, M, Chen, YDI, Concas, MP, Connell, J, de Mutsert, R, de Silva, HJ, de Vries, PS, Demirkan, Ayse, Ding, JZ (Jing Zhong), Eaton, CB, Faul, JD, Friedlander, Y, Gabriel, KP, Ghanbari, Mohsen, Giulianini, F, Gu, CC, Gu, DF, Harris, TB, He, J, Heikkinen, S, Heng, CK, Hunt, SC, Ikram, Arfan, Jonas, JB, Koh, WP, Komulainen, P, Krieger, JE, Kritchevsky, SB, Kutalik, Z, Kuusisto, J, Langefeld, CD, Langenberg, C, Launer, LJ, Leander, K, Lemaitre, RN, Lewis, CE, Liang, JJ, Alizadeh, BZ, Boezen, HM, Franke, L, Navis, G, Rots, M, Swertz, M, Wolffenbuttel, BHR, Wijmenga, C, Liu, JJ, Maagi, R, Manichaikul, A, Meitinger, T, Metspalu, A, Milaneschi, Y, Mohlke, KL, Mosley, TH, Murray, AD, Nalls, MA, Nang, EEK, Nelson, CP, Nona, S, Norris, JM, Nwuba, CV, O'Connell, J, Palmer, ND, Papanicolau, GJ, Pazoki, R, Pedersen, NL, Peters, A, Peyser, PA, Polasek, O, Porteous, DJ, Poveda, A, Raitakari, OT, Rich, SS, Risch, N, Robinson, JG, Rose, LM, Rudan, I, Schreiner, PJ, Scott, RA, Sidney, SS, Sims, M, Smith, JA, Snieder, H, Sofer, T, Starr, JM, Sternfeld, B, Strauch, K, Tang, H, Taylor, KD, Tsai, MY, Tuomilehto, J, Uitterlinden, André, van der Ende, MY, van Heemst, D, Voortman, Trudy, Waldenberger, M, Wennberg, P, Wilson, G, Xiang, YB, Yao, J, Yu, CZ, Yuan, JM, Zhao, W, Zonderman, AB, Becker, DM, Boehnke, M, Bowden, DW, de Faire, U, Deary, IJ, Elliott, P, Esko, T, Freedman, BI, Froguel, P, Gasparini, P, Gieger, C, Kato, N, Laakso, M, Lakka, TA, Lehtimaki, T, Magnusson, PKE, Oldehinkel, AJ, Penninx, B, Samani, NJ, Shu, XO, van der Harst, P, van Vliet-Ostaptchouk, JV, Vollenweider, P, Wagenknecht, LE, Wang, YX, Wareham, NJ, Weir, DR, Wu, TC, Zheng, W, Zhu, XF, Evans, MK, Franks, PW, Gudnason, V, Hayward, C, Horta, BL, Kelly, TN, Liu, YM, North, KE, Pereira, AC, Ridker, PM, Tai, ES, van Dam, RM, Fox, ER, Kardia, SLR, Liu, CT, Mook, Dennis, Province, MA, Redline, S, Duijn, Cornelia, Rotter, JI, Kooperberg, CB, Gauderman, WJ, Psaty, BM, Rice, K, Munroe, PB, Fornage, M, Cupples, LA, Rotimi, CN, Morrison, AC, Rao, DC, and Loos, RJF
Published: 2019

47. GWAS and colocalization analyses implicate carotid intima-media thickness and carotid plaque loci in cardiovascular outcomes

Author: Franceschini, N, Giambartolomei, C, de Vries, PS, Finan, C, Bis, JC, Huntley, RP, Lovering, RC, Tajuddin, SM, Winkler, TW, Graff, M, Kavousi, M, Dale, C, Smith, AV, Hofer, E, van Leeuwen, EM, Nolte, IM, Lu, L, Scholz, M, Sargurupremraj, M, Pitkänen, N, Franzén, O, Joshi, PK, Noordam, R, Marioni, RE, Hwang, SJ, Musani, SK, Schminke, U, Palmas, W, Isaacs, A, Correa, A, Zonderman, AB, Hofman, A, Teumer, A, Cox, AJ, Uitterlinden, AG, Wong, A, Smit, AJ, Newman, AB, Britton, A, Ruusalepp, A, Sennblad, B, Hedblad, B, Pasaniuc, B, Penninx, BW, Langefeld, CD, Wassel, CL, Tzourio, C, Fava, C, Baldassarre, D, O’Leary, DH, Teupser, D, Kuh, D, Tremoli, E, Mannarino, E, Grossi, E, Boerwinkle, E, Schadt, EE, Ingelsson, E, Veglia, F, Rivadeneira, F, Beutner, F, Chauhan, G, Heiss, G, Snieder, H, Campbell, H, Völzke, H, Markus, HS, Deary, IJ, Jukema, JW, de Graaf, J, Price, J, Pott, J, Hopewell, JC, Liang, J, Thiery, J, Engmann, J, Gertow, K, Rice, K, Taylor, KD, Dhana, K, Kiemeney, LALM, Lind, L, Raffield, LM, Launer, LJ, Holdt, LM, Dörr, M, Dichgans, M, Traylor, M, Sitzer, M, Kumari, M, Kivimaki, M, Nalls, MA, Melander, O, Raitakari, O, Franco, OH, Rueda-Ochoa, OL, Roussos, P, Whincup, PH, Amouyel, P, and Giral, P
Subjects: Aging, MEGASTROKE Consortium, Quantitative Trait Loci, ADAMTS9 Protein, Coronary Disease, Cardiovascular, Polymorphism, Single Nucleotide, Carotid Intima-Media Thickness, Protein-Lysine 6-Oxidase, Risk Factors, Genetics, 2.1 Biological and endogenous factors, Humans, Genetic Predisposition to Disease, cardiovascular diseases, Aetiology, Polymorphism, Heart Disease - Coronary Heart Disease, Plaque, Atherosclerotic, Human Genome, Single Nucleotide, Atherosclerosis, Plaque, Atherosclerotic, Brain Disorders, Stroke, Heart Disease, cardiovascular system, Amino Acid Oxidoreductases, Lod Score, Genome-Wide Association Study
Abstract: © 2018, The Author(s). Carotid artery intima media thickness (cIMT) and carotid plaque are measures of subclinical atherosclerosis associated with ischemic stroke and coronary heart disease (CHD). Here, we undertake meta-analyses of genome-wide association studies (GWAS) in 71,128 individuals for cIMT, and 48,434 individuals for carotid plaque traits. We identify eight novel susceptibility loci for cIMT, one independent association at the previously-identified PINX1 locus, and one novel locus for carotid plaque. Colocalization analysis with nearby vascular expression quantitative loci (cis-eQTLs) derived from arterial wall and metabolic tissues obtained from patients with CHD identifies candidate genes at two potentially additional loci, ADAMTS9 and LOXL4. LD score regression reveals significant genetic correlations between cIMT and plaque traits, and both cIMT and plaque with CHD, any stroke subtype and ischemic stroke. Our study provides insights into genes and tissue-specific regulatory mechanisms linking atherosclerosis both to its functional genomic origins and its clinical consequences in humans.
Published: 2018

48. Genome-wide association study of 23,500 individuals identifies 7 loci associated with brain ventricular volume

Author: Vojinovic, D, Adams, HH, Jian, X, Yang, Q, Smith, AV, Bis, JC, Teumer, A, Scholz, M, Armstrong, NJ, Hofer, E, Saba, Y, Luciano, M, Bernard, M, Trompet, S, Yang, J, Gillespie, NA, van der Lee, SJ, Neumann, A, Ahmad, S, Andreassen, OA, Ames, D, Amin, N, Arfanakis, K, Bastin, ME, Becker, DM, Beiser, AS, Beyer, F, Brodaty, H, Bryan, RN, Bülow, R, Dale, AM, De Jager, PL, Deary, IJ, DeCarli, C, Fleischman, DA, Gottesman, RF, van der Grond, J, Gudnason, V, Harris, TB, Homuth, G, Knopman, DS, Kwok, JB, Lewis, CE, Li, S, Loeffler, M, Lopez, OL, Maillard, P, El Marroun, H, Mather, KA, Mosley, TH, Muetzel, RL, Nauck, M, Nyquist, PA, Panizzon, MS, Pausova, Z, Psaty, BM, Rice, K, Rotter, JI, Royle, N, Satizabal, CL, Schmidt, R, Schofield, PR, Schreiner, PJ, Sidney, S, Stott, DJ, Thalamuthu, A, Uitterlinden, AG, and Valdés Hernández, MC
Abstract: © 2018, The Author(s). The volume of the lateral ventricles (LV) increases with age and their abnormal enlargement is a key feature of several neurological and psychiatric diseases. Although lateral ventricular volume is heritable, a comprehensive investigation of its genetic determinants is lacking. In this meta-analysis of genome-wide association studies of 23,533 healthy middle-aged to elderly individuals from 26 population-based cohorts, we identify 7 genetic loci associated with LV volume. These loci map to chromosomes 3q28, 7p22.3, 10p12.31, 11q23.1, 12q23.3, 16q24.2, and 22q13.1 and implicate pathways related to tau pathology, S1P signaling, and cytoskeleton organization. We also report a significant genetic overlap between the thalamus and LV volumes (?genetic = -0.59, p-value = 3.14 × 10-6), suggesting that these brain structures may share a common biology. These genetic associations of LV volume provide insights into brain morphology.
Published: 2018
Full Text: View/download PDF

49. Publisher Correction: Genetic analysis of over 1 million people identifies 535 new loci associated with blood pressure traits (vol 50, pg 1412, 2018)

Author: Evangelou, E, Warren, HR, Mosen-Ansorena, D, Mifsud, B, Pazoki, R, Gao, H, Ntritsos, G, Dimou, N, Cabrera, CP, Karaman, I, Fu, LN, Evangelou, M, Witkowska, K, Tzanis, E, Hellwege, JN, Giri, A, Edwards, DRV, Sun, YV, Cho, K, Gaziano, JM, Wilson, PWF, Tsao, PS, Kovesdy, CP, Esko, T, Magi, R, Milani, L, Almgren, P, Boutin, T, Debette, S, Ding, J, Giulianini, F, Holliday, EG, Jackson, AU, Li-Gao, R, Lin, W-Y, Luan, J, Mangino, M, Oldmeadow, C, Prins, BP, Qian, Y, Sargurupremraj, M, Shah, N, Surendran, P, Theriault, S, Verweij, N, Willems, SM, Zhao, J-H, Amouyel, P, Connell, J, De Mutsert, R, Doney, ASF, Farrall, M, Menni, C, Morris, AD, Noordam, R, Pare, G, Poulter, NR, Shields, DC, Stanton, A, Thom, S, Abecasis, G, Amin, N, Arking, DE, Ayers, KL, Barbieri, CM, Batini, C, Bis, JC, Blake, T, Bochud, M, Boehnke, M, Boerwinkle, E, Boomsma, DI, Bottinger, EP, Braund, PS, Brumat, M, Campbell, A, Campbell, H, Chakravarti, A, Chambers, JC, Chauhan, G, Ciullo, M, Cocca, M, Collins, F, Cordell, HJ, Davies, G, De Borst, MH, De Geus, EJ, Deary, IJ, Deelen, J, Del Greco, FM, Demirkale, CY, Dorr, M, Ehret, GB, Elosua, R, Enroth, S, Erzurumluoglu, AM, Ferreira, T, Franberg, M, Franco, OH, Gandin, I, Gasparini, P, Giedraitis, V, Gieger, C, Girotto, G, Goel, A, Gow, AJ, Gudnason, V, Guo, X, Gyllensten, U, Hamsten, A, Harris, TB, Harris, SE, Hartman, CA, Havulinna, AS, Hicks, AA, Hofer, E, Hofman, A, Hottenga, J-J, Huffman, JE, Hwang, S-J, Ingelsson, E, James, A, Jansen, R, Jarvelin, M-R, Joehanes, R, Johansson, A, Johnson, AD, Joshi, PK, Jousilahti, P, Jukema, JW, Jula, A, Kahonen, M, Kathiresan, S, Keavney, BD, Khaw, K-T, Knekt, P, Knight, J, Kolcic, I, Kooner, JS, Koskinen, S, Kristiansson, K, Kutalik, Z, Laan, M, Larson, M, Launer, LJ, Lehne, B, Lehtimaki, T, Liewald, DCM, Lin, L, Lind, L, Lindgren, CM, Liu, Y, Loos, RJF, Lopez, LM, Lu, Y, Lyytikainen, L-P, Mahajan, A, Mamasoula, C, Marrugat, J, Marten, J, Milaneschi, Y, Morgan, A, Morris, AP, Morrison, AC, Munson, PJ, Nalls, MA, Nandakumar, P, Nelson, CP, Niiranen, T, Nolte, IM, Nutile, T, Oldehinkel, AJ, Oostra, BA, O'Reilly, PF, Org, E, Padmanabhan, S, Palmas, W, Palotie, A, Pattie, A, Penninx, BWJH, Perola, M, Peters, A, Polasek, O, Pramstaller, PP, Quang, TN, Raitakari, OT, Ren, M, Rettig, R, Rice, K, Ridker, PM, Ried, JS, Riese, H, Ripatti, S, Robino, A, Rose, LM, Rotter, JI, Rudan, I, Ruggiero, D, Saba, Y, Sala, CF, Salomaa, V, Samani, NJ, Sarin, A-P, Schmidt, R, Schmidt, H, Shrine, N, Siscovick, D, Smith, AV, Snieder, H, Sober, S, Sorice, R, Starr, JM, Stott, DJ, Strachan, DP, Strawbridge, RJ, Sundstrom, J, Swertz, MA, Taylor, KD, Teumer, A, Tobin, MD, Tomaszewski, M, Toniolo, D, Traglia, M, Trompet, S, Tuomilehto, J, Tzourio, C, Uitterlinden, AG, Vaez, A, Van der Most, PJ, Van Duijn, CM, Vergnaud, A-C, Verwoert, GC, Vitart, V, Volker, U, Vollenweider, P, Vuckovic, D, Watkins, H, Wild, SH, Willemsen, G, Wilson, JF, Wright, AF, Yao, J, Zemunik, T, Zhang, W, Attia, JR, Butterworth, AS, Chasman, DI, Conen, D, Cucca, F, Danesh, J, Hayward, C, Howson, JMM, Laakso, M, Lakatta, EG, Langenberg, C, Melander, O, Mook-Kanamori, DO, Palmer, CNA, Risch, L, Scott, RA, Scott, RJ, Sever, P, Spector, TD, Van der Harst, P, Wareham, NJ, Zeggini, E, Levy, D, Munroe, PB, Newton-Cheh, C, Brown, MJ, Metspalu, A, Hung, AM, O'Donnell, CJ, Edwards, TL, Psaty, BM, Tzoulaki, I, Barnes, MR, Wain, LV, Elliott, P, and Caulfield, MJ
Subjects: Genetics & Heredity, Science & Technology, Million Veteran Program, 06 Biological Sciences, Life Sciences & Biomedicine, 11 Medical and Health Sciences, Developmental Biology
Abstract: Correction to: Nature Genetics https://doi.org/10.1038/s41588-018-0205-x, published online 17 September 2018.
Published: 2018

50. Genome-Wide Association Study Meta-Analysis of the Alcohol Use Disorders Identification Test (AUDIT) in Two Population-Based Cohorts

Author: Sanchez-Roige, S, Palmer, AA, Fontanillas, P, Elson, SL, 23andMe Research Team, Substance Use Disorder Working Group of the Psychiatric Genomics Consortium, Adams, MJ, Howard, DM, Edenberg, HJ, Davies, G, Crist, RC, Deary, IJ, McIntosh, AM, and Clarke, T-K
Subjects: Substance Use Disorder Working Group of the Psychiatric Genomics Consortium, 23andMe Research Team
Abstract: OBJECTIVE::Alcohol use disorders are common conditions that have enormous social and economic consequences. Genome-wide association analyses were performed to identify genetic variants associated with a proxy measure of alcohol consumption and alcohol misuse and to explore the shared genetic basis between these measures and other substance use, psychiatric, and behavioral traits. METHOD::This study used quantitative measures from the Alcohol Use Disorders Identification Test (AUDIT) from two population-based cohorts of European ancestry (UK Biobank [N=121,604] and 23andMe [N=20,328]) and performed a genome-wide association study (GWAS) meta-analysis. Two additional GWAS analyses were performed, a GWAS for AUDIT scores on items 1-3, which focus on consumption (AUDIT-C), and for scores on items 4-10, which focus on the problematic consequences of drinking (AUDIT-P). RESULTS::The GWAS meta-analysis of AUDIT total score identified 10 associated risk loci. Novel associations localized to genes including JCAD and SLC39A13; this study also replicated previously identified signals in the genes ADH1B, ADH1C, KLB, and GCKR. The dimensions of AUDIT showed positive genetic correlations with alcohol consumption (rg=0.76-0.92) and DSM-IV alcohol dependence (rg=0.33-0.63). AUDIT-P and AUDIT-C scores showed significantly different patterns of association across a number of traits, including psychiatric disorders. AUDIT-P score was significantly positively genetically correlated with schizophrenia (rg=0.22), major depressive disorder (rg=0.26), and attention deficit hyperactivity disorder (rg=0.23), whereas AUDIT-C score was significantly negatively genetically correlated with major depressive disorder (rg=-0.24) and ADHD (rg=-0.10). This study also used the AUDIT data in the UK Biobank to identify thresholds for dichotomizing AUDIT total score that optimize genetic correlations with DSM-IV alcohol dependence. Coding individuals with AUDIT total scores ≤4 as control subjects and those with scores ≥12 as case subjects produced a significant high genetic correlation with DSM-IV alcohol dependence (rg=0.82) while retaining most subjects. CONCLUSIONS::AUDIT scores ascertained in population-based cohorts can be used to explore the genetic basis of both alcohol consumption and alcohol use disorders.
Published: 2018
Full Text: View/download PDF

Catalog

Books, media, physical & digital resources

See catalog results

Searchworks

Select search scope, currently: Articles Catalog books, media & more in Jio Institute collections Articles journal articles & other e-resources

Search

Search Constraints

Refine your results

Search Limiters

Topic

Publication Year Range

Language

Publication Type

Journal

Region

Database

Publisher

1,652 results on '"Deary, IJ."'

Search Results

Catalog

Select search scope, currently: Articles

Catalog

books, media & more in Jio Institute collections

Articles

journal articles & other e-resources