Genetic Overlap Between Attention-Deficit/Hyperactivity Disorder and Bipolar Disorder: Evidence From Genome-wide Association Study Meta-analysis.
Genetic Overlap Between Attention-Deficit/Hyperactivity Disorder and Bipolar Disorder: Evidence From Genome-wide Association Study Meta-analysis.
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DOI：
10.1016/j.biopsych.2016.08.040
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发表时间：
2017-11-01
影响因子：
10.6
通讯作者：
Reif A
中科院分区：
文献类型：
--
作者：
van Hulzen KJE;Scholz CJ;Franke B;Ripke S;Klein M;McQuillin A;Sonuga-Barke EJ;PGC ADHD Working Group;Kelsoe JR;Landén M;Andreassen OA;PGC Bipolar Disorder Working Group;Lesch KP;Weber H;Faraone SV;Arias-Vasquez A;Reif A
注意缺陷/多动障碍（ADHD）和双相情感障碍（BPD）是经常共存且高度遗传性的精神健康状况。我们假设早发年龄（≤21岁）的BPD病例特别可能与ADHD表现出基因共变。GWAS数据包括4609名ADHD患者、9650名BPD患者（其中5167名早发性BPD）和21363名典型发展对照。我们进行了一项跨障碍GWAS荟萃分析，以确定观察到的ADHD和BPD之间的共病是否可能是由于共同的遗传风险。我们发现，在完全和年龄限制样本中，ADHD和BPD之间存在显著的基于snp的遗传相关性（rGfull = 0.64, p = 3.13×10−14;rGrestricted = 0.71, p = 4.09×10−16）。在全BPD样本之间的meta分析发现了位于6号染色体（CEP85L）和10号染色体（TAF9BP2）上的两个全基因组显著区域（prs7089973 = 2.47×10−8;Prs11756438 = 4.36×10−8）。将分析限制在早期发病的BPD病例中，在ADCY2基因的5号染色体上发现了一个全基因组显著关联（prs58502974 = 2.11×10−8）。其他被发现的名义上重要的区域包含已知的eqtl，其功能可能影响NT5DC1、NT5DC2和CACNB3的表达，而功能预测暗示ABLIM1是神经元组织中等位基因特异性表达的基因。ADHD和BPD之间基于snp的遗传相关性是实质性的，显著的，并且与ADHD和BPD之间存在遗传重叠一致，可能存在早期和晚期BPD发病的差异遗传机制。
Attention-deficit/hyperactivity disorder (ADHD) and bipolar disorder (BPD) are frequently co-occurring and highly heritable mental health conditions. We hypothesized that BPD cases with an early age of onset (≤21 years) would be particularly likely to show genetic covariation with ADHD. GWAS data were available for 4,609 individuals with ADHD, 9,650 individuals with BPD (5,167 thereof with early-onset BPD) and 21,363 typically developing controls. We conducted a cross-disorder GWAS meta-analysis to identify whether the observed comorbidity between ADHD and BPD could be due to shared genetic risks. We found a significant SNP-based genetic correlation between ADHD and BPD in the full and age-restricted samples (rGfull = 0.64, p = 3.13×10−14; rGrestricted = 0.71, p = 4.09×10−16). The meta-analysis between the full BPD sample identified two genome-wide significant (prs7089973 = 2.47×10−8; Prs11756438 = 4.36×10−8) regions located on chromosomes 6 (CEP85L) and 10 (TAF9BP2). Restricting the analyses to BPD cases with an early onset yielded one genome-wide significant association (prs58502974 = 2.11×10−8) on chromosome 5 in the ADCY2 gene. Additional nominally significant regions identified contained known eQTLs with putative functional consequences for NT5DC1, NT5DC2 and CACNB3 expression, while functional predictions implicated ABLIM1 as an allele-specifically expressed gene in neuronal tissue. The SNP-based genetic correlation between ADHD and BPD is substantial, significant, and consistent with the existence of genetic overlap between ADHD and BPD, with potential differential genetic mechanisms involved in early and later BPD onset.
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影响因子：
11
作者：
Bavamian, S.;Mellios, N.;Lalonde, J.;Fass, D. M.;Wang, J.;Sheridan, S. D.;Madison, J. M.;Zhou, Fen;Rueckert, E. H.;Barker, D.;Perlis, R. H.;Sur, M.;Haggarty, S. J.
通讯作者：
Haggarty, S. J.
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
30.8
作者：
Bulik-Sullivan, Brendan K.;Loh, Po-Ru;Finucane, Hilary K.;Ripke, Stephan;Yang, Jian;Patterson, Nick;Daly, Mark J.;Price, Alkes L.;Neale, Benjamin M.
通讯作者：
Neale, Benjamin M.
影响因子：
12.3
作者：
Carroll LS;Owen MJ
通讯作者：
Owen MJ
影响因子：
11
作者：
Li, M.;Luo, X-j;Rietschel, M.;Lewis, C. M.;Mattheisen, M.;Mueller-Myhsok, B.;Jamain, S.;Leboyer, M.;Landen, M.;Thompson, P. M.;Cichon, S.;Noethen, M. M.;Schulze, T. G.;Sullivan, P. F.;Bergen, S. E.;Donohoe, G.;Morris, D. W.;Hargreaves, A.;Gill, M.;Corvin, A.;Hultman, C.;Toga, A. W.;Shi, L.;Lin, Q.;Shi, H.;Gan, L.;Meyer-Lindenberg, A.;Czamara, D.;Henry, C.;Etain, B.;Bis, J. C.;Ikram, M. A.;Fornage, M.;Debette, S.;Launer, L. J.;Seshadri, S.;Erk, S.;Walter, H.;Heinz, A.;Bellivier, F.;Stein, J. L.;Medland, S. E.;Vasquez, A. Arias;Hibar, D. P.;Franke, B.;Martin, N. G.;Wright, M. J.;Su, B.
通讯作者：
Su, B.