Recent Submissions

  • Investigation of parent-of-origin effects in ADHD candidate genes

    Kim, Jang Woo; Waldman, Irwin D.; Faraone, Stephen V.; Biederman, Joseph; Doyle, Alysa E.; Purcell, Shaun; Arbeitman, Lori; Fagerness, Jesen; Sklar, Pamela; Smoller, Jordan W. (Wiley, 2007)
  • The new neuropsychiatric genetics

    Faraone, S.V.; Smoller, J.W.; Pato, C.N.; Sullivan, P.; Tsuang, M.T. (Wiley, 2008-01-05)
  • Pediatric mania: a developmental subtype of bipolar disorder?

    Biederman, Joseph; Mick, Eric; Faraone, Stephen V; Spencer, Thomas; Wilens, Timothy E; Wozniak, Janet (Elsevier BV, 2000-09)
  • Agonal factors distort gene-expression patterns in human postmortem brains

    Dai, Jiacheng; Chen, Yu; Chen, Chao; Liu, Chunyu (Cold Spring Harbor Laboratory, 2020-07-12)
    Agonal factors, the conditions that occur just prior to death, can impact the molecular quality of postmortem brains, influencing gene expression results. Nevertheless, study designs using postmortem brain tissue rarely, if ever, account for these factors, and previous studies had not documented nor adjusted for agonal factors. Our study used gene expression data of 262 samples from ROSMAP with the following terminal states recorded for each donor: surgery, fever, infection, unconsciousness, difficulty breathing, and mechanical ventilation. Performed differential gene expression and weighted gene co-expression network analyses (WGCNA), fever and infection were the primary contributors to brain gene expression changes. Fever and infection also contributed to brain cell-type specific gene expression and cell proportion changes. Furthermore, the gene expression patterns implicated in fever and infection were unique to other agonal factors. We also found that previous studies of gene expression in postmortem brains were confounded by variables of hypoxia or oxygen level pathways. Therefore, correction for agonal factors through probabilistic estimation of expression residuals (PEER) or surrogate variable analysis (SVA) is recommended to control for unknown agonal factors. Our analyses revealed fever and infection contributing to gene expression changes in postmortem brains and emphasized the necessity of study designs that document and account for agonal factors.
  • Risk variants and polygenic architecture of disruptive behavior disorders in the context of attention-deficit/hyperactivity disorder

    Demontis, Ditte; Walters, Raymond K.; Rajagopal, Veera M.; Waldman, Irwin D.; Grove, Jakob; Als, Thomas D.; Dalsgaard, Søren; Ribasés, Marta; Bybjerg-Grauholm, Jonas; Bækvad-Hansen, Maria; et al. (Springer Science and Business Media LLC, 2021-01-25)
    Attention-Deficit/Hyperactivity Disorder (ADHD) is a childhood psychiatric disorder often comorbid with disruptive behavior disorders (DBDs). Here, we report a GWAS meta-analysis of ADHD comorbid with DBDs (ADHD + DBDs) including 3802 cases and 31,305 controls. We identify three genome-wide significant loci on chromosomes 1, 7, and 11. A meta-analysis including a Chinese cohort supports that the locus on chromosome 11 is a strong risk locus for ADHD + DBDs across European and Chinese ancestries (rs7118422, P = 3.15×10-10, OR = 1.17). We find a higher SNP heritability for ADHD + DBDs (h2SNP = 0.34) when compared to ADHD without DBDs (h2SNP = 0.20), high genetic correlations between ADHD + DBDs and aggressive (rg = 0.81) and anti-social behaviors (rg = 0.82), and an increased burden (polygenic score) of variants associated with ADHD and aggression in ADHD + DBDs compared to ADHD without DBDs. Our results suggest an increased load of common risk variants in ADHD + DBDs compared to ADHD without DBDs, which in part can be explained by variants associated with aggressive behavior.
  • Comorbidity of ADHD and adult bipolar disorder: A systematic review and meta-analysis

    Schiweck, Carmen; Arteaga-Henriquez, Gara; Aichholzer, Mareike; Edwin Thanarajah, Sharmili; Vargas-Cáceres, Sebastian; Matura, Silke; Grimm, Oliver; Haavik, Jan; Kittel-Schneider, Sarah; Ramos-Quiroga, Josep Antoni; et al. (Elsevier BV, 2021-05)
    Attention-deficit / hyperactivity disorder (ADHD) and Bipolar Disorder (BD) are common mental disorders with a high degree of comorbidity. However, no systematic review with meta-analysis has aimed to quantify the degree of comorbidity between both disorders. To this end we performed a systematic search of the literature in October 2020. In a meta-analysis of 71 studies with 646,766 participants from 18 countries, it was found that about one in thirteen adults with ADHD was also diagnosed with BD (7.95 %; 95 % CI: 5.31-11.06), and nearly one in six adults with BD had ADHD (17.11 %; 95 % CI: 13.05-21.59 %). Substantial heterogeneity of comorbidity rates was present, highlighting the importance of contextual factors: Heterogeneity could partially be explained by diagnostic system, sample size and geographical location. Age of BD onset occurred earlier in patients with comorbid ADHD (3.96 years; 95 % CI: 2.65-5.26, p < 0.001). Cultural and methodological differences deserve attention for evaluating diagnostic criteria and clinicians should be aware of the high comorbidity rates to prevent misdiagnosis and provide optimal care for both disorders.
  • DRAMS: A tool to detect and re-align mixed-up samples for integrative studies of multi-omics data

    Jiang, Yi; Giase, Gina; Grennan, Kay; Shieh, Annie W.; Xia, Yan; Han, Lide; Wang, Quan; Wei, Qiang; Chen, Rui; Liu, Sihan; et al. (Public Library of Science (PLoS), 2020-04-13)