title: The genetic basis of the comorbidity between cannabis use and major depression.
abstract: While the prevalence of major depression is elevated among cannabis users, the role of genetics in this pattern of comorbidity is not clear. This study aimed to estimate the heritability of cannabis use and major depression, quantify the genetic overlap between these two traits and localize regions of the genome that segregate in families with cannabis use and major depression.
  
  
  
  Family-based univariate and bivariate genetic analysis.
  
  
  
  San Antonio, Texas, USA.
  
  
  
  Genetics of Brain Structure and Function study (GOBS) participants: 1284 Mexican Americans from 75 large multi-generation families and an additional 57 genetically unrelated spouses.
  
  
  
  Phenotypes of life-time history of cannabis use and major depression, measured using the semistructured MINI-Plus interview. Genotypes measured using ~1 M single nucleotide polymorphisms (SNPs) on Illumina BeadChips. A subselection of these SNPs were used to build multi-point identity-by-descent matrices for linkage analysis.
  
  
  
  Both cannabis use [h2= 0.614, P = 1.00 × 10-6, standard error (SE) = 0.151] and major depression (h2= 0.349, P = 1.06 × 10-5, SE = 0.100) are heritable traits, and there is significant genetic correlation between the two (ρg= 0.424, P = 0.0364, SE = 0.195). Genome-wide linkage scans identify a significant univariate linkage peak for major depression on chromosome 22 [logarithm of the odds (LOD) = 3.144 at 2 centimorgans (cM)], with a suggestive peak for cannabis use on chromosome 21 (LOD = 2.123 at 37 cM). A significant pleiotropic linkage peak influencing both cannabis use and major depression was identified on chromosome 11 using a bivariate model (LOD = 3.229 at 112 cM). Follow-up of this pleiotropic signal identified a SNP 20 kb upstream of NCAM1 (rs7932341) that shows significant bivariate association (P = 3.10 × 10-5). However, this SNP is rare (seven minor allele carriers) and does not drive the linkage signal observed.
  
  
  
  There appears to be a significant genetic overlap between cannabis use and major depression among Mexican Americans, a pleiotropy that appears to be localized to a region on chromosome 11q23 that has been linked previously to these phenotypes.
authors: Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
authors: Karen
authors: K
authors: Hodgson
authors: South Texas Diabetes and Obesity Institute, University of Texas Health Science Center at San Antonio and University of Texas of the Rio Grande Valley, Brownsville, TX, USA.
authors: Laura
authors: L
authors: Almasy
authors: Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
authors: Emma E M
authors: EE
authors: Knowles
authors: Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX, USA.
authors: Jack W
authors: JW
authors: Kent
authors: South Texas Diabetes and Obesity Institute, University of Texas Health Science Center at San Antonio and University of Texas of the Rio Grande Valley, Brownsville, TX, USA.
authors: Joanne E
authors: JE
authors: Curran
authors: South Texas Diabetes and Obesity Institute, University of Texas Health Science Center at San Antonio and University of Texas of the Rio Grande Valley, Brownsville, TX, USA.
authors: Thomas D
authors: TD
authors: Dyer
authors: South Texas Diabetes and Obesity Institute, University of Texas Health Science Center at San Antonio and University of Texas of the Rio Grande Valley, Brownsville, TX, USA.
authors: Harald H H
authors: HH
authors: Göring
authors: Department of Psychiatry, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
authors: Rene L
authors: RL
authors: Olvera
authors: Research Imaging Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
authors: Mary D
authors: MD
authors: Woolsey
authors: South Texas Diabetes and Obesity Institute, University of Texas Health Science Center at San Antonio and University of Texas of the Rio Grande Valley, Brownsville, TX, USA.
authors: Ravi
authors: R
authors: Duggirala
authors: Research Imaging Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.|South Texas Veterans Health System, San Antonio, TX, USA.
authors: Peter T
authors: PT
authors: Fox
authors: South Texas Diabetes and Obesity Institute, University of Texas Health Science Center at San Antonio and University of Texas of the Rio Grande Valley, Brownsville, TX, USA.
authors: John
authors: J
authors: Blangero
authors: 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: David C
authors: DC
authors: Glahn
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015897:Comorbidity; D003865:Major Depressive Disorder / Q000453:epidemiology* / Q000235:genetics; D005006:Ethnicity / Q000523:psychology / Q000706:statistics & numerical data; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology*; D006801:Humans; D008297:Male; D002189:Marijuana Abuse / Q000453:epidemiology* / Q000235:genetics; D008875:Middle Aged; D013781:Texas / Q000453:epidemiology; D055815:Young Adult
keywords: Cannabis; comorbidity; genetics; linkage; major depression; pleiotropy