title: Genome-wide linkage on chromosome 10q26 for a dimensional scale of major depression.
abstract: Major depressive disorder (MDD) is a common and potentially life-threatening mood disorder. Identifying genetic markers for depression might provide reliable indicators of depression risk, which would, in turn, substantially improve detection, enabling earlier and more effective treatment. The aim of this study was to identify rare variants for depression, modeled as a continuous trait, using linkage and post-hoc association analysis. The sample comprised 1221 Mexican-American individuals from extended pedigrees. A single dimensional scale of MDD was derived using confirmatory factor analysis applied to all items from the Past Major Depressive Episode section of the Mini-International Neuropsychiatric Interview. Scores on this scale of depression were subjected to linkage analysis followed by QTL region-specific association analysis. Linkage analysis revealed a single genome-wide significant QTL (LOD=3.43) on 10q26.13, QTL-specific association analysis conducted in the entire sample revealed a suggestive variant within an intron of the gene LHPP (rs11245316, p=7.8×10(-04); LD-adjusted Bonferroni-corrected p=8.6×10(-05)). This region of the genome has previously been implicated in the etiology of MDD; the present study extends our understanding of the involvement of this region by highlighting a putative gene of interest (LHPP).
authors.affiliation: Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA; Olin Neuropsychiatric Research Center, Institute of Living, Hartford Hospital, Hartford, CT, USA. Electronic address: emma.knowles@yale.edu.
authors.forename: Emma E M
authors.initials: EE
authors.lastname: Knowles
authors.affiliation: Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX, USA.
authors.forename: Jack W
authors.initials: JW
authors.lastname: Kent
authors.affiliation: Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA; Olin Neuropsychiatric Research Center, Institute of Living, Hartford Hospital, Hartford, CT, USA.
authors.forename: D Reese
authors.initials: DR
authors.lastname: McKay
authors.affiliation: Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA; Olin Neuropsychiatric Research Center, Institute of Living, Hartford Hospital, Hartford, CT, USA.
authors.forename: Emma
authors.initials: E
authors.lastname: Sprooten
authors.affiliation: Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA; Olin Neuropsychiatric Research Center, Institute of Living, Hartford Hospital, Hartford, CT, USA.
authors.forename: Samuel R
authors.initials: SR
authors.lastname: Mathias
authors.affiliation: South Texas Diabetes and Obesity Institute, University of Texas Health Science Center at San Antonio & University of Texas of the Rio Grande Valley, Brownsville, TX, United States.
authors.forename: Joanne E
authors.initials: JE
authors.lastname: Curran
authors.affiliation: Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX, USA.
authors.forename: Melanie A
authors.initials: MA
authors.lastname: Carless
authors.affiliation: South Texas Diabetes and Obesity Institute, University of Texas Health Science Center at San Antonio & University of Texas of the Rio Grande Valley, Brownsville, TX, United States.
authors.forename: Marcio A A
authors.initials: MA
authors.lastname: de Almeida
authors.affiliation: South Texas Diabetes and Obesity Institute, University of Texas Health Science Center at San Antonio & University of Texas of the Rio Grande Valley, Brownsville, TX, United States.
authors.forename: H H Goring
authors.initials: HH
authors.lastname: Harald
authors.affiliation: South Texas Diabetes and Obesity Institute, University of Texas Health Science Center at San Antonio & University of Texas of the Rio Grande Valley, Brownsville, TX, United States.
authors.forename: Tom D
authors.initials: TD
authors.lastname: Dyer
authors.affiliation: Department of Psychiatry, University of Texas Health Science Center San Antonio, Texas Center San Antonio, San Antonio, TX, United States.
authors.forename: Rene L
authors.initials: RL
authors.lastname: Olvera
authors.affiliation: Research Imaging Institute, University of Texas Health Science Center San Antonio, San Antonio, TX, United States; South Texas Veterans' Healthcare System, 7400 Merton Minter, San Antonio, TX 78229, USA.
authors.forename: Peter T
authors.initials: PT
authors.lastname: Fox
authors.affiliation: South Texas Diabetes and Obesity Institute, University of Texas Health Science Center at San Antonio & University of Texas of the Rio Grande Valley, Brownsville, TX, United States.
authors.forename: Ravi
authors.initials: R
authors.lastname: Duggirala
authors.affiliation: South Texas Diabetes and Obesity Institute, University of Texas Health Science Center at San Antonio & University of Texas of the Rio Grande Valley, Brownsville, TX, United States.
authors.forename: Laura
authors.initials: L
authors.lastname: Almasy
authors.affiliation: South Texas Diabetes and Obesity Institute, University of Texas Health Science Center at San Antonio & University of Texas of the Rio Grande Valley, Brownsville, TX, United States.
authors.forename: John
authors.initials: J
authors.lastname: Blangero
authors.affiliation: Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA; Olin Neuropsychiatric Research Center, Institute of Living, Hartford Hospital, Hartford, CT, USA.
authors.forename: David C
authors.initials: DC
authors.lastname: Glahn
mesh_terms: D002879:Chromosomes, Human, Pair 10; D003865:Major Depressive Disorder / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008126:Lod Score; D008297:Male; D008875:Middle Aged; D010641:Phenotype
chemical_list: D005819:Genetic Markers