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JOURNAL ARTICLE
Alexis C Edwards, Henrik Ohlsson, Jessica E Salvatore, Mallory E Stephenson, Casey Crump, Jan Sundquist, Kristina Sundquist, Kenneth S Kendler
BACKGROUND: Prior research has reported an association between divorce and suicide attempt. We aimed to clarify this complex relationship, considering sex differences, temporal factors, and underlying etiologic pathways. METHODS: We used Swedish longitudinal national registry data for a cohort born 1960-1990 that was registered as married between 1978 and 2018 ( N = 1 601 075). We used Cox proportional hazards models to estimate the association between divorce and suicide attempt...
December 12, 2023: Psychological Medicine
#22
JOURNAL ARTICLE
Polygenic analyses show important differences between MDD symptoms collected using PHQ9 and CIDI-SF.
Lianyun Huang, Sonja Tang, Jolien Rietkerk, Vivek Appadurai, Morten Dybdahl Krebs, Andrew J Schork, Thomas Werge, Verena Zuber, Kenneth Kendler, Na Cai
BACKGROUND: Symptoms of Major Depressive Disorder (MDD) are commonly assessed using self-rating instruments like the Patient Health Questionnaire 9 (PHQ9, current symptoms), and the Composite International Diagnostic Interview Short-Form (CIDI-SF, worst-episode symptoms). We perform a systematic comparison between them for their genetics and utility in investigating MDD heterogeneity. METHODS: Using data from the UKBiobank (N = 41948 - 109417), we assess the SNP heritability (h2) and genetic correlation (rG) of both sets of MDD symptoms...
December 4, 2023: Biological Psychiatry
#23
JOURNAL ARTICLE
Sonja LaBianca, Isabell Brikell, Dorte Helenius, Robert Loughnan, Joel Mefford, Clare E Palmer, Rebecca Walker, Jesper R Gådin, Morten Krebs, Vivek Appadurai, Morteza Vaez, Esben Agerbo, Marianne Giørtz Pedersen, Anders D Børglum, David M Hougaard, Ole Mors, Merete Nordentoft, Preben Bo Mortensen, Kenneth S Kendler, Terry L Jernigan, Daniel H Geschwind, Andrés Ingason, Andrew W Dahl, Noah Zaitlen, Søren Dalsgaard, Thomas M Werge, Andrew J Schork
Attention deficit hyperactivity disorder (ADHD) is a complex disorder that manifests variability in long-term outcomes and clinical presentations. The genetic contributions to such heterogeneity are not well understood. Here we show several genetic links to clinical heterogeneity in ADHD in a case-only study of 14,084 diagnosed individuals. First, we identify one genome-wide significant locus by comparing cases with ADHD and autism spectrum disorder (ASD) to cases with ADHD but not ASD. Second, we show that cases with ASD and ADHD, substance use disorder and ADHD, or first diagnosed with ADHD in adulthood have unique polygenic score (PGS) profiles that distinguish them from complementary case subgroups and controls...
November 30, 2023: Nature Genetics
#24
JOURNAL ARTICLE
Kenneth S Kendler, Virginia Justis
While the origins of two of Kraepelin's three subtypes of dementia praecox (DP), catatonic and hebephrenic, are well understood, no similar clear narrative exists for his concepts of paranoia and paranoid DP, which require a consideration of both German and French sources. An important milestone in the French literature is the massive 524 page monograph entitled "Le Délire Des Persécutions" published in 1871 by Henri Legrand du Saulle which contained extensive, clinically detailed descriptions of a wide range of cases with prominent, organized persecutory delusions...
November 22, 2023: Schizophrenia Bulletin
#25
JOURNAL ARTICLE
Ulzee An, Ali Pazokitoroudi, Marcus Alvarez, Lianyun Huang, Silviu Bacanu, Andrew J Schork, Kenneth Kendler, Päivi Pajukanta, Jonathan Flint, Noah Zaitlen, Na Cai, Andy Dahl, Sriram Sankararaman
Biobanks that collect deep phenotypic and genomic data across many individuals have emerged as a key resource in human genetics. However, phenotypes in biobanks are often missing across many individuals, limiting their utility. We propose AutoComplete, a deep learning-based imputation method to impute or 'fill-in' missing phenotypes in population-scale biobank datasets. When applied to collections of phenotypes measured across ~300,000 individuals from the UK Biobank, AutoComplete substantially improved imputation accuracy over existing methods...
November 20, 2023: Nature Genetics
#26
JOURNAL ARTICLE
Andrew Dahl, Michael Thompson, Ulzee An, Morten Krebs, Vivek Appadurai, Richard Border, Silviu-Alin Bacanu, Thomas Werge, Jonathan Flint, Andrew J Schork, Sriram Sankararaman, Kenneth S Kendler, Na Cai
Biobanks often contain several phenotypes relevant to diseases such as major depressive disorder (MDD), with partly distinct genetic architectures. Researchers face complex tradeoffs between shallow (large sample size, low specificity/sensitivity) and deep (small sample size, high specificity/sensitivity) phenotypes, and the optimal choices are often unclear. Here we propose to integrate these phenotypes to combine the benefits of each. We use phenotype imputation to integrate information across hundreds of MDD-relevant phenotypes, which significantly increases genome-wide association study (GWAS) power and polygenic risk score (PRS) prediction accuracy of the deepest available MDD phenotype in UK Biobank, LifetimeMDD...
November 20, 2023: Nature Genetics
#27
REVIEW
Kenneth S Kendler, Astrid Klee
In the 1899 6th edition of his influential textbook, Kraepelin proposed a diagnostic category of "Old-Age Paranoid Psychosis." In this 1930 article, Bruno Schulz studied the morbid risk (MR) of several disorders and traits in the parents, siblings, offspring, and nieces/nephews of 51 probands with "Old-Age Paranoid Psychosis." His results permitted an evaluation of the validity of Kraepelin's category of Old-Age Paranoid Psychosis, in particular, whether it was a form of psychosis resulting from "senile changes" or late-onset schizophrenia...
November 15, 2023: American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics
#28
Hanna M van Loo, Ymkje Anna de Vries, Jacob Taylor, Luka Todorovic, Camille Dollinger, Kenneth S Kendler
Bipolar disorder is a heterogenous condition with a varied clinical presentation. While progress has been made in identifying genetic variants associated with bipolar disorder, most common genetic variants have not yet been identified. More detailed phenotyping (beyond diagnosis) may increase the chance of finding genetic variants. Our aim therefore was to identify clinical characteristics that index genetic differences in bipolar disorder.We performed a systematic review of all genome-wide molecular genetic, family, and twin studies investigating familial/genetic influences on the clinical characteristics of bipolar disorder...
November 15, 2023: Molecular Psychiatry
#29
REVIEW
Kenneth S Kendler, Astrid Klee
In 1936, Bruno Schulz published the first detailed, book-length review of the methodology of psychiatric genetic research, based on his experiences at the German Research Institute of Psychiatry. Emphasis is placed on proper selection of relatives and the ascertainment corrections required for Mendelian transmission models. Twin studies are considered as is the impact of reduced fertility on patterns of risk. For the field work, Schulz emphasizes the importance of trust-building, confidentiality, collateral informants, and the use of medical and other administrative records, all ideally stored in personal files...
November 6, 2023: American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics
#30
REVIEW
Kenneth S Kendler, Virginia Justis
Boven published, in 1915, his MD thesis at the University of Lausanne in which he examined 60 3- to 4-generation pedigrees ascertained from admitted patients with dementia praecox (DP) and manic-depressive insanity (MDI). He asked three questions: (i) were DP and MDI hereditary? (ii) were they the same or distinct conditions? and (iii) were they Mendelian disorders? Based on the rarity of environmental precipitants severe enough to cause disorder onset and the pattern of disorders in relatives, Boven concluded that both disorders were inherited...
October 19, 2023: American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics
#31
JOURNAL ARTICLE
Ananda B Amstadter, Sara Lönn, Jan Sundquist, Kristina Sundquist, Kenneth S Kendler
Background: There are two primary phenotypic models of comorbidity between post-traumatic stress disorder (PTSD) and drug use disorder (DUD), i.e. self-medication (PTSD precedes and causes DUD) and susceptibility (DUD precedes and causes PTSD). We sought to clarify the longitudinal relationship between PTSD and DUD, while examining sex differences. Method: We used approximately 23 years of longitudinal data from Swedish population registries to conduct two complementary statistical models: Cox proportional hazard models ( N ≈ 1...
2023: European Journal of Psychotraumatology
#32
JOURNAL ARTICLE
Anna R Docherty, Niamh Mullins, Allison E Ashley-Koch, Xuejun Qin, Jonathan R I Coleman, Andrey Shabalin, JooEun Kang, Balasz Murnyak, Frank Wendt, Mark Adams, Adrian I Campos, Emily DiBlasi, Janice M Fullerton, Henry R Kranzler, Amanda V Bakian, Eric T Monson, Miguel E Rentería, Consuelo Walss-Bass, Ole A Andreassen, Chittaranjan Behera, Cynthia M Bulik, Howard J Edenberg, Ronald C Kessler, J John Mann, John I Nurnberger, Giorgio Pistis, Fabian Streit, Robert J Ursano, Renato Polimanti, Michelle Dennis, Melanie Garrett, Lauren Hair, Philip Harvey, Elizabeth R Hauser, Michael A Hauser, Jennifer Huffman, Daniel Jacobson, Ravi Madduri, Benjamin McMahon, David W Oslin, Jodie Trafton, Swapnil Awasthi, Wade H Berrettini, Martin Bohus, Xiao Chang, Hsi-Chung Chen, Wei J Chen, Erik D Christensen, Scott Crow, Philibert Duriez, Alexis C Edwards, Fernando Fernández-Aranda, Hanga Galfalvy, Michael Gandal, Philip Gorwood, Yiran Guo, Jonathan D Hafferty, Hakon Hakonarson, Katherine A Halmi, Akitoyo Hishimoto, Sonia Jain, Stéphane Jamain, Susana Jiménez-Murcia, Craig Johnson, Allan S Kaplan, Walter H Kaye, Pamela K Keel, James L Kennedy, Minsoo Kim, Kelly L Klump, Daniel F Levey, Dong Li, Shih-Cheng Liao, Klaus Lieb, Lisa Lilenfeld, Christian R Marshall, James E Mitchell, Satoshi Okazaki, Ikuo Otsuka, Dalila Pinto, Abigail Powers, Nicolas Ramoz, Stephan Ripke, Stefan Roepke, Vsevolod Rozanov, Stephen W Scherer, Christian Schmahl, Marcus Sokolowski, Anna Starnawska, Michael Strober, Mei-Hsin Su, Laura M Thornton, Janet Treasure, Erin B Ware, Hunna J Watson, Stephanie H Witt, D Blake Woodside, Zeynep Yilmaz, Lea Zillich, Rolf Adolfsson, Ingrid Agartz, Martin Alda, Lars Alfredsson, Vivek Appadurai, María Soler Artigas, Sandra Van der Auwera, M Helena Azevedo, Nicholas Bass, Claiton H D Bau, Bernhard T Baune, Frank Bellivier, Klaus Berger, Joanna M Biernacka, Tim B Bigdeli, Elisabeth B Binder, Michael Boehnke, Marco P Boks, David L Braff, Richard Bryant, Monika Budde, Enda M Byrne, Wiepke Cahn, Enrique Castelao, Jorge A Cervilla, Boris Chaumette, Aiden Corvin, Nicholas Craddock, Srdjan Djurovic, Jerome C Foo, Andreas J Forstner, Mark Frye, Justine M Gatt, Ina Giegling, Hans J Grabe, Melissa J Green, Eugenio H Grevet, Maria Grigoroiu-Serbanescu, Blanca Gutierrez, Jose Guzman-Parra, Marian L Hamshere, Annette M Hartmann, Joanna Hauser, Stefanie Heilmann-Heimbach, Per Hoffmann, Marcus Ising, Ian Jones, Lisa A Jones, Lina Jonsson, René S Kahn, John R Kelsoe, Kenneth S Kendler, Stefan Kloiber, Karestan C Koenen, Manolis Kogevinas, Marie-Odile Krebs, Mikael Landén, Marion Leboyer, Phil H Lee, Douglas F Levinson, Calwing Liao, Jolanta Lissowska, Fermin Mayoral, Susan L McElroy, Patrick McGrath, Peter McGuffin, Andrew McQuillin, Divya Mehta, Ingrid Melle, Philip B Mitchell, Esther Molina, Gunnar Morken, Caroline Nievergelt, Markus M Nöthen, Michael C O'Donovan, Roel A Ophoff, Michael J Owen, Carlos Pato, Michele T Pato, Brenda W J H Penninx, James B Potash, Robert A Power, Martin Preisig, Digby Quested, Josep Antoni Ramos-Quiroga, Andreas Reif, Marta Ribasés, Vanesa Richarte, Marcella Rietschel, Margarita Rivera, Andrea Roberts, Gloria Roberts, Guy A Rouleau, Diego L Rovaris, Alan R Sanders, Peter R Schofield, Thomas G Schulze, Laura J Scott, Alessandro Serretti, Jianxin Shi, Lea Sirignano, Pamela Sklar, Olav B Smeland, Jordan W Smoller, Edmund J S Sonuga-Barke, Maciej Trzaskowski, Ming T Tsuang, Gustavo Turecki, Laura Vilar-Ribó, John B Vincent, Henry Völzke, James T R Walters, Cynthia Shannon Weickert, Thomas W Weickert, Myrna M Weissman, Leanne M Williams, Naomi R Wray, Clement C Zai, Esben Agerbo, Anders D Børglum, Gerome Breen, Ditte Demontis, Annette Erlangsen, Joel Gelernter, Stephen J Glatt, David M Hougaard, Hai-Gwo Hwu, Po-Hsiu Kuo, Cathryn M Lewis, Qingqin S Li, Chih-Min Liu, Nicholas G Martin, Andrew M McIntosh, Sarah E Medland, Ole Mors, Merete Nordentoft, Catherine M Olsen, David Porteous, Daniel J Smith, Eli A Stahl, Murray B Stein, Danuta Wasserman, Thomas Werge, David C Whiteman, Virginia Willour, Hilary Coon, Jean C Beckham, Nathan A Kimbrel, Douglas M Ruderfer
OBJECTIVE: Suicidal behavior is heritable and is a major cause of death worldwide. Two large-scale genome-wide association studies (GWASs) recently discovered and cross-validated genome-wide significant (GWS) loci for suicide attempt (SA). The present study leveraged the genetic cohorts from both studies to conduct the largest GWAS meta-analysis of SA to date. Multi-ancestry and admixture-specific meta-analyses were conducted within groups of significant African, East Asian, and European ancestry admixtures...
October 1, 2023: American Journal of Psychiatry
#33
JOURNAL ARTICLE
Séverine Lannoy, Henrik Ohlsson, Kenneth S Kendler, Mallory Stephenson, Jan Sundquist, Kristina Sundquist, Alexis C Edwards
BACKGROUND AND AIMS: Alcohol use disorder (AUD) is one of the strongest predictors of suicidal behavior. Here, we measured risk of suicide attempt and death as a function of AUD typologies. DESIGN: We used AUD typologies from previous latent class analysis: (i) externalizing subtype (characterized by externalizing symptomatology and early age of onset; individuals in this group have lower education and higher familial/social difficulties); (ii) subtype described by minimal psychopathology; and (iii) internalizing subtype (characterized by internalizing symptomatology and later age of onset; individuals in this group have higher education)...
September 26, 2023: Addiction
#34
Mohammad Ahangari, Amanda Elswick Gentry, Mohammed F Hassan, Tan Hoang Nguyen, Kenneth S Kendler, Silviu-Alin Bacanu, Roseann E Peterson, Brien P Riley, Bradley T Webb
Alcohol use disorder (AUD) is moderately heritable with significant social and economic impact. Genome-wide association studies (GWAS) have identified common variants associated with AUD, however, rare variant investigations have yet to achieve well-powered sample sizes. In this study, we conducted an interval-based exome-wide analysis of the Alcohol Use Disorder Identification Test Problems subscale (AUDIT-P) using both machine learning (ML) predicted risk and empirical functional weights. This research has been conducted using the UK Biobank Resource (application number 30782...
September 15, 2023: bioRxiv
#35
JOURNAL ARTICLE
Lauren N Ross, Kenneth S Kendler, James F Woodward
We explore Madole & Harden's (2022) suggestion that single-nucleotide polymorphism (SNP)/trait correlations are analogous to randomized experiments and thus can be given a causal interpretation.
September 11, 2023: Behavioral and Brain Sciences
#36
JOURNAL ARTICLE
Natassia Robinson, Alexander Ploner, Roxana Müller-Eberstein, Paul Lichtenstein, Kenneth S Kendler, Sarah E Bergen
OBJECTIVE: Prior studies report increased risk of schizophrenia (SCZ) in migrants relative to the native-born population; however, few have investigated bipolar disorder (BD) and migrant characteristics which may influence risk. We aimed to examine the risk of SCZ and BD in migrants and their children relative to those of Swedish ancestry, and whether risk varied by age at migration, region of origin, sex, and parental migrant status. METHODS: We conducted a nested case-control study using 5539 SCZ cases and 20,577 BD cases diagnosed 1988-2013, individually matched to five population-based controls by birth year and sex...
September 2, 2023: Schizophrenia Research
#37
JOURNAL ARTICLE
Sara L Lönn, Mary G Krauland, Abigail A Fagan, Jan Sundquist, Kristina Sundquist, Mark S Roberts, Kenneth S Kendler
OBJECTIVE: Drug use disorder (DUD) is a world-wide problem and strategies to reduce its incidence are central to decreasing its burden. This investigation seeks to provide a proof of concept for the ability of agent-based modeling to predict the impact of the introduction of an effective school-based intervention, the Good Behavior Game (GBG), on reducing DUD in Scania, Sweden primarily through increasing school achievement. METHOD: We modified an existing agent-based simulation model of opioid use disorder to represent DUD use in Scania County, southern Sweden...
August 30, 2023: Journal of Studies on Alcohol and Drugs
#38
JOURNAL ARTICLE
Alexis C Edwards, Henrik Ohlsson, Séverine Lannoy, Mallory Stephenson, Casey Crump, Jan Sundquist, Kenneth S Kendler, Kristina Sundquist
BACKGROUND: Greater alcohol accessibility, for example in the form of a high density of alcohol outlets or low alcohol taxation rates, may be associated with increased risk of suicidal behavior. However, most studies have been conducted at the aggregate level, and some have not accounted for potential confounders such as socioeconomic position or neighborhood quality. METHODS: In a Swedish cohort of young adults aged 18 to 25, we used logistic regressions to evaluate whether living in a neighborhood that included bars, nightclubs, and/or government alcohol outlets was associated with risk of suicide attempt (SA) or suicide death (SD) during four separate 2-year observation periods...
May 2023: Alcohol (Hanover)
#39
JOURNAL ARTICLE
Martin Tesli, Ragnar Nesvåg, Unn K Haukvik, Kristin Gustavson, Natalia Tesli, Christine Friestad, Torbjørn Skardhamar, Øyvind Naess, Nikolai Czajkowski, Kenneth S Kendler, Ted Reichborn-Kjennerud, Eivind Ystrom
INTRODUCTION: Psychotic-like experiences (PLE) have been associated with the subsequent emergence of psychotic disorders as well as several other domains of psychopathology. In this twin study, we estimated the genetic and environmental correlations between PLE and 10 personality disorders (PD). METHODS: Diagnoses of 10 PDs according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) and PLE from the Composite International Diagnostic Interview (CIDI) were retrieved for 2793 young adult twins from the Norwegian Twin Registry...
July 27, 2023: Acta Psychiatrica Scandinavica
#40
JOURNAL ARTICLE
Kenneth S Kendler, Henrik Ohlsson, Jan Sundquist, Kristina Sundquist
BACKGROUND: Does the genetic aptitude for educational attainment (GAEA) moderate the genetic risk for alcohol use disorder (AUD) and drug use disorder (DUD)? METHODS: In the native Swedish population, born 1960-1980 and followed through 2017 ( n = 1 862 435), the family genetic risk score (FGRS) for AUD and DUD and GAEA were calculated from, respectively, the educational attainment and risk for AUD and DUD, of 1st through 5th degree relatives from Swedish national registers...
May 2023: Psychological Medicine
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