OBJECTIVE: The purpose of this study was to find loci for major depression via linkage analysis of a large sibling pair sample. METHOD: The authors conducted a genome-wide linkage analysis of 839 families consisting of 971 affected sibling pairs with severe recurrent major depression, comprising waves I and II of the Depression Network Study cohort. In addition to examining affected status, linkage analyses in the full data set were performed using diagnoses restricted by impairment severity, and association mapping of hits in a large case-control data set was attempted. RESULTS: The authors identified genome-wide significant linkage to chromosome 3p25-26 when the diagnoses were restricted by severity, which was a maximum LOD score of 4.0 centered at the linkage marker D3S1515. The linkage signal identified was genome-wide significant after correction for the multiple phenotypes tested, although subsequent association mapping of the region in a genome-wide association study of a U.K. depression sample did not provide significant results. CONCLUSIONS: The authors report a genome-wide significant locus for depression that implicates genes that are highly plausible for involvement in the etiology of recurrent depression. Despite the fact that association mapping in the region was negative, the linkage finding was replicated by another group who found genome-wide-significant linkage for depression in the same region. This suggests that 3p25-26 is a new locus for severe recurrent depression. This represents the first report of a genome-wide significant locus for depression that also has an independent genome-wide significant replication.
OBJECTIVE: The purpose of this study was to find loci for major depression via linkage analysis of a large sibling pair sample. METHOD: The authors conducted a genome-wide linkage analysis of 839 families consisting of 971 affected sibling pairs with severe recurrent major depression, comprising waves I and II of the Depression Network Study cohort. In addition to examining affected status, linkage analyses in the full data set were performed using diagnoses restricted by impairment severity, and association mapping of hits in a large case-control data set was attempted. RESULTS: The authors identified genome-wide significant linkage to chromosome 3p25-26 when the diagnoses were restricted by severity, which was a maximum LOD score of 4.0 centered at the linkage marker D3S1515. The linkage signal identified was genome-wide significant after correction for the multiple phenotypes tested, although subsequent association mapping of the region in a genome-wide association study of a U.K. depression sample did not provide significant results. CONCLUSIONS: The authors report a genome-wide significant locus for depression that implicates genes that are highly plausible for involvement in the etiology of recurrent depression. Despite the fact that association mapping in the region was negative, the linkage finding was replicated by another group who found genome-wide-significant linkage for depression in the same region. This suggests that 3p25-26 is a new locus for severe recurrent depression. This represents the first report of a genome-wide significant locus for depression that also has an independent genome-wide significant replication.
Authors: Samuel R Mathias; Emma E M Knowles; Jack W Kent; D Reese McKay; Joanne E Curran; Marcio A A de Almeida; Thomas D Dyer; Harald H H Göring; Rene L Olvera; Ravi Duggirala; Peter T Fox; Laura Almasy; John Blangero; David C Glahn Journal: Hum Brain Mapp Date: 2015-10-20 Impact factor: 5.038
Authors: Craig W Lindsley; Kyle A Emmitte; Corey R Hopkins; Thomas M Bridges; Karen J Gregory; Colleen M Niswender; P Jeffrey Conn Journal: Chem Rev Date: 2016-02-16 Impact factor: 60.622
Authors: Teodor T Postolache; Laura Del Bosque-Plata; Serge Jabbour; Michael Vergare; Rongling Wu; Claudia Gragnoli Journal: Am J Med Genet B Neuropsychiatr Genet Date: 2019-02-06 Impact factor: 3.568
Authors: Bradley T Webb; An-Yuan Guo; Brion S Maher; Zhongming Zhao; Edwin J van den Oord; Kenneth S Kendler; Brien P Riley; Nathan A Gillespie; Carol A Prescott; Christel M Middeldorp; Gonneke Willemsen; Eco Jc de Geus; Jouke-Jan Hottenga; Dorret I Boomsma; Eline P Slagboom; Naomi R Wray; Grant W Montgomery; Nicholas G Martin; Margie J Wright; Andrew C Heath; Pamela A Madden; Joel Gelernter; James A Knowles; Steven P Hamilton; Myrna M Weissman; Abby J Fyer; Patricia Huezo-Diaz; Peter McGuffin; Anne Farmer; Ian W Craig; Cathryn Lewis; Pak Sham; Raymond R Crowe; Jonathan Flint; John M Hettema Journal: Eur J Hum Genet Date: 2012-04-04 Impact factor: 4.246
Authors: David C Glahn; Joanne E Curran; Anderson M Winkler; Melanie A Carless; Jack W Kent; Jac C Charlesworth; Matthew P Johnson; Harald H H Göring; Shelley A Cole; Thomas D Dyer; Eric K Moses; Rene L Olvera; Peter Kochunov; Ravi Duggirala; Peter T Fox; Laura Almasy; John Blangero Journal: Biol Psychiatry Date: 2011-10-07 Impact factor: 13.382
Authors: Michele L Pergadia; Anne L Glowinski; Naomi R Wray; Arpana Agrawal; Scott F Saccone; Anu Loukola; Ulla Broms; Tellervo Korhonen; Brenda W J H Penninx; Julia D Grant; Elliot C Nelson; Anjali K Henders; Andrew J Schrage; Yi-Ling Chou; Kaisu Keskitalo-Vuokko; Qin Zhu; Scott D Gordon; Jacqueline M Vink; Eco J C de Geus; Stuart Macgregor; Jimmy Z Liu; Gonneke Willemsen; Sarah E Medland; Dorret I Boomsma; Grant W Montgomery; John P Rice; Alison M Goate; Andrew C Heath; Jaakko Kaprio; Nicholas G Martin; Pamela A F Madden Journal: Am J Psychiatry Date: 2011-05-15 Impact factor: 18.112
Authors: Carson W Reed; Jacob J Kalbfleisch; Madison J Wong; Jordan P Washecheck; Ashton Hunter; Alice L Rodriguez; Anna L Blobaum; P Jeffrey Conn; Colleen M Niswender; Craig W Lindsley Journal: ACS Med Chem Lett Date: 2020-08-20 Impact factor: 4.345
Authors: Karin Hek; Ayse Demirkan; Jari Lahti; Antonio Terracciano; Alexander Teumer; Cornelia M van Duijn; Hans J Grabe; Lenore J Launer; Kathryn L Lunetta; Thomas H Mosley; Anne B Newman; Henning Tiemeier; Joanne Murabito; Marilyn C Cornelis; Najaf Amin; Erin Bakshis; Jens Baumert; Jingzhong Ding; Yongmei Liu; Kristin Marciante; Osorio Meirelles; Michael A Nalls; Yan V Sun; Nicole Vogelzangs; Lei Yu; Stefania Bandinelli; Emelia J Benjamin; David A Bennett; Dorret Boomsma; Alessandra Cannas; Laura H Coker; Eco de Geus; Philip L De Jager; Ana V Diez-Roux; Shaun Purcell; Frank B Hu; Eric B Rimma; David J Hunter; Majken K Jensen; Gary Curhan; Kenneth Rice; Alan D Penman; Jerome I Rotter; Nona Sotoodehnia; Rebecca Emeny; Johan G Eriksson; Denis A Evans; Luigi Ferrucci; Myriam Fornage; Vilmundur Gudnason; Albert Hofman; Thomas Illig; Sharon Kardia; Margaret Kelly-Hayes; Karestan Koenen; Peter Kraft; Maris Kuningas; Joseph M Massaro; David Melzer; Antonella Mulas; Cornelis L Mulder; Anna Murray; Ben A Oostra; Aarno Palotie; Brenda Penninx; Astrid Petersmann; Luke C Pilling; Bruce Psaty; Rajesh Rawal; Eric M Reiman; Andrea Schulz; Joshua M Shulman; Andrew B Singleton; Albert V Smith; Angelina R Sutin; André G Uitterlinden; Henry Völzke; Elisabeth Widen; Kristine Yaffe; Alan B Zonderman; Francesco Cucca; Tamara Harris; Karl-Heinz Ladwig; David J Llewellyn; Katri Räikkönen; Toshiko Tanaka Journal: Biol Psychiatry Date: 2013-01-03 Impact factor: 13.382
Authors: David C Glahn; Emma E M Knowles; D Reese McKay; Emma Sprooten; Henriette Raventós; John Blangero; Irving I Gottesman; Laura Almasy Journal: Am J Med Genet B Neuropsychiatr Genet Date: 2014-01-24 Impact factor: 3.568
Authors: Emma E M Knowles; Jack W Kent; D Reese McKay; Emma Sprooten; Samuel R Mathias; Joanne E Curran; Melanie A Carless; Marcio A A de Almeida; H H Goring Harald; Tom D Dyer; Rene L Olvera; Peter T Fox; Ravi Duggirala; Laura Almasy; John Blangero; David C Glahn Journal: J Affect Disord Date: 2015-11-17 Impact factor: 4.839