Discovery of the first genome-wide significant risk loci for attention deficit/hyperactivity disorder

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Demontis D, Walters RK, Martin J, Mattheisen M, Als TD, Agerbo E, Baldursson G, Belliveau R, Bybjerg-Grauholm J, Bækvad-Hansen M, Cerrato F, Chambert K, Churchhouse C, Dumont A, Eriksson N, Gandal M, Goldstein JI, Grasby KL, Grove J, Gudmundsson OO, Hansen CS, Hauberg ME, Hollegaard MV, Howrigan DP, Huang H, Maller JB, Martin AR, Martin NG, Moran J, Pallesen J, Palmer DS, Pedersen CB, Pedersen MG, Poterba T, Poulsen JB, Ripke S, Robinson EB, Satterstrom FK, Stefansson H, Stevens C, Turley P, Walters GB, Won H, Wright MJ, Andreassen OA, Asherson P, Burton CL, Boomsma DI, Cormand B, Dalsgaard S, Franke B, Gelernter J, Geschwind D, Hakonarson H, Haavik J, Kranzler HR, Kuntsi J, Langley K, Lesch KP, Middeldorp C, Reif A, Rohde LA, Roussos P, Schachar R, Sklar P, Sonuga-Barke EJS, Sullivan PF, Thapar A, Tung JY, Waldman ID, Medland SE, Stefansson K, Nordentoft M, Hougaard DM, Werge T, Mors O, Mortensen PB, Daly MJ, Faraone SV, Børglum AD, Neale BM. Discovery of the first genome-wide significant risk loci for attention deficit/hyperactivity disorder. Nat Genet. 2019 Jan;51(1):63-75. Epub 2018 Nov 26

Identification of common genetic risk variants for autism spectrum disorder

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Grove J, Ripke S, Als TD, Mattheisen M, Walters RK, Won H, Pallesen J, Agerbo E, Andreassen OA, Anney R, Awashti S, Belliveau R, Bettella F, Buxbaum JD, Bybjerg-Grauholm J, Bækvad-Hansen M, Cerrato F, Chambert K, Christensen JH, Churchhouse C, Dellenvall K, Demontis D, De Rubeis S, Devlin B, Djurovic S, Dumont AL, Goldstein JI, Hansen CS, Hauberg ME, Hollegaard MV, Hope S, Howrigan DP, Huang H, Hultman CM, Klei L, Maller J, Martin J, Martin AR, Moran JL, Nyegaard M, Nærland T, Palmer DS, Palotie A, Pedersen CB, Pedersen MG, dPoterba T, Poulsen JB, Pourcain BS, Qvist P, Rehnström K, Reichenberg A, Reichert J, Robinson EB, Roeder K, Roussos P, Saemundsen E, Sandin S, Satterstrom FK, Davey Smith G, Stefansson H, Steinberg S, Stevens CR, Sullivan PF, Turley P, Walters GB, Xu X, Stefansson K, Geschwind DH, Nordentoft M, Hougaard DM, Werge T, Mors O, Mortensen PB, Neale BM, Daly MJ, Børglum AD. Identification of common genetic risk variants for autism spectrum disorder. Nat Genet. 2019 Mar;51(3):431-444. Epub 2019 Feb 25

Comparative genetic architectures of schizophrenia in East Asian and European populations

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Lam M, Chen CY, Li Z, Martin A, Bryois J, Ma X, Gaspar H, Ikeda M, Benyamin B, Brown B, Liu R, Zhou W, Guan L, Kamatani Y, Kim SW, Kubo M, Kusumawardhani A, Liu CM, Ma H, Periyasamy S, Takahashi A, Wang Q, Xu Z, Yu H, Zhu F, Psychiatric Genomics Consortium Schizophrenia Working Group, Indonesia Schizophrenia Consortium, Genetic REsearch on schizophreniA neTwork-China, Netherland GREAT-CN, Chen W, Faraone S, Glatt S, He L, Hyman S, Hwu HG, Li T, McCarroll S, Neale B, Sklar P, Wildenauer D, Yu X, Zhang D, Mowry B, Lee J, Holmans P, Xu S, Sullivan P, Ripke S, O’Donovan M, Daly M, Qin S, Sham P, Iwata N, Hong K, Schwab S, Yue W, Tsuang M, Liu J, Ma X, Kahn R, Shi Y, and Huang H. Comparative genetic architectures of schizophrenia in East Asian and European populations., Nature genetics, 51(12), 1670–1678.

Genome-wide Association Studies in Ancestrally Diverse Populations: Opportunities, Methods, Pitfalls, and Recommendation

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Peterson RE, Kuchenbaecker K, Walters RK, Chen CY, Popejoy AB, Periyasamy S, Lam M, Iyegbe C, Strawbridge RJ, Brick L, Carey CE, Martin AR, Meyers JL, Su J, Chen J, Edwards AC, Kalungi A, Koen N, Majara L, Schwarz E, Smoller JW, Stahl EA, Sullivan PF, Vassos E, Mowry B, Prieto ML, Cuellar-Barboza A, Bigdeli TB, Edenberg HJ, Huang H, Duncan LE. Genome-wide Association Studies in Ancestrally Diverse Populations: Opportunities, Methods, Pitfalls, and Recommendations. Cell. 2019 Oct 17;179(3):589-603. Epub 2019 Oct 10.

Contribution of copy number variants to schizophrenia from a genome-wide study of 41,321 subjects

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Lam M, Chen CY, Li Z, Martin A, Bryois J, Ma X, Gaspar H, Ikeda M, Benyamin B, Brown B, Liu R, Zhou W, Guan L, Kamatani Y, Kim SW, Kubo M, Kusumawardhani A, Liu CM, Ma H, Periyasamy S, Takahashi A, Xu Z, Yu H, Zhu F, Psychiatric Genomics Consortium Schizophrenia Working Group, Indonesia Schizophrenia Consortium, Genetic REsearch on schizophreniA neTwork-China, Netherland GREAT-CN, Chen W, Faraone S, Glatt S, He L, Hyman S, Hwu HG, Li T, McCarroll S, Neale B, Sklar P, Wildenauer D, Yu X, Zhang D, Mowry B, Lee J, Holmans P, Xu S, Sullivan P, Ripke S, O’Donovan M, Daly M, Qin S, Sham P, Iwata N, Hong K, Schwab S, Yue W, Tsuang M, Liu J, Ma X, Kahn R, Shi Y, and Huang H. Comparative genetic architectures of schizophrenia in East Asian and European populations., Nature Genetics (accepted on June 5 2019)

Blood transcriptomic comparison of individuals with and without autism spectrum disorder: A combined-samples mega-analysis

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Peterson RE, Kuchenbaecker K, Walters RK, Chen CY, Popejoy AB, Periyasamy S, Lam M, Iyegbe C, Strawbridge RJ, Brick L, Carey CE, Martin AR, Meyers JL, Su J, Chen J, Edwards AC, Kalungi A, Koen N, Majara L, Schwarz E, Smoller JW, Stahl EA, Sullivan PF, Vassos E, Mowry B, Prieto ML, Cuellar-Barboza A, Bigdeli TB, Edenberg HJ, Huang H, Duncan LE. Genome-wide Association Studies in Ancestrally Diverse Populations: Opportunities, Methods, Pitfalls, and Recommendations. Cell. 2019 Oct 17;179(3):589-603. Epub 2019 Oct 10.

Whole genome sequencing in psychiatric disorders: the WGSPD consortium

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Sanders SJ, Neale BM, Huang H, Werling DM, An JY, Dong S, Abecasis G, Arguello PA, Blangero J, Boehnke M, Daly MJ, Eggan K, Geschwind DH, Glahn DC, Goldstein DB, Gur RE, Handsaker RE, McCarroll SA, Ophoff RA, Palotie A, Pato CN, Sabatti C, State MW, Willsey AJ, Hyman SE, Addington AM, Lehner T, Freimer NB. Whole genome sequencing in psychiatric disorders: the WGSPD consortium. Nat Neurosci. 2017 Dec;20(12):1661-1668. Review

Clozapine-induced agranulocytosis is associated with rare HLA-DQB1 and HLA-B alleles

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Jacqueline I Goldstein, Fredrik L Jarskog, Chris Hilliard, Ana Alfirevic, Laramie Duncan, Denis Fourches, Hailiang Huang, Monkol Lek, Benjamin M Neale, Stephan Ripke, Kevin Shianna, Jin P Szatkiewicz, Alexander Tropsha, Edwin JCG van den Oord, Ingolf Cascorbi, Michael Dettling, Ephraim Gazit, Donald C Goff, Arthur L Holden, Deanna L Kelly, Anil K Malhotra, Jimmi Nielsen, Munir Pirmohamed, Dan Rujescu, Thomas Werge, Deborah L Levy, Richard C Josiassen, James L Kennedy, Jeffrey A Lieberman, Mark J Daly, and Patrick F Sullivan. 2014. “Clozapine-induced agranulocytosis is associated with rare HLA-DQB1 and HLA-B alleles.” Nat Commun, 5, Pp. 4757. Abstract

Clozapine is a particularly effective antipsychotic medication but its use is curtailed by the risk of clozapine-induced agranulocytosis/granulocytopenia (CIAG), a severe adverse drug reaction occurring in up to 1% of treated individuals. Identifying genetic risk factors for CIAG could enable safer and more widespread use of clozapine. Here we perform the largest and most comprehensive genetic study of CIAG to date by interrogating 163 cases using genome-wide genotyping and whole-exome sequencing. We find that two loci in the major histocompatibility complex are independently associated with CIAG: a single amino acid in HLA-DQB1 (126Q) (P=4.7 × 10(-14), odds ratio (OR)=0.19, 95% confidence interval (CI)=0.12-0.29) and an amino acid change in the extracellular binding pocket of HLA-B (158T) (P=6.4 × 10(-10), OR=3.3, 95% CI=2.3-4.9). These associations dovetail with the roles of these genes in immunogenetic phenotypes and adverse drug responses for other medications, and provide insight into the pathophysiology of CIAG.