The genetic basis of the comorbidity between cannabis use and major depression

Karen Hodgson, Laura Almasy, Emma E M Knowles, Jack W. Kent, Joanne E. Curran, Thomas D. Dyer, Harald H H Göring, Rene L Olvera, Mary D. Woolsey, Ravi Duggirala, Peter T Fox, John Blangero, David C. Glahn

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Background and aims: 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. Design: Family-based univariate and bivariate genetic analysis. Setting: San Antonio, Texas, USA. Participants: 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. Measurements: 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. Findings: 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. Conclusions: 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.

Original languageEnglish (US)
JournalAddiction
DOIs
StateAccepted/In press - 2016

Fingerprint

Cannabis
Comorbidity
Depression
Single Nucleotide Polymorphism
Genome
Phenotype
Chromosomes, Human, Pair 22
Chromosomes, Human, Pair 21
Chromosomes, Human, Pair 11
Genetic Structures
Spouses
Chromosomes
Alleles
Genotype
Interviews
Brain

Keywords

  • Cannabis
  • Comorbidity
  • Genetics
  • Linkage
  • Major depression
  • Pleiotropy

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Psychiatry and Mental health

Cite this

Hodgson, K., Almasy, L., Knowles, E. E. M., Kent, J. W., Curran, J. E., Dyer, T. D., ... Glahn, D. C. (Accepted/In press). The genetic basis of the comorbidity between cannabis use and major depression. Addiction. https://doi.org/10.1111/add.13558

The genetic basis of the comorbidity between cannabis use and major depression. / Hodgson, Karen; Almasy, Laura; Knowles, Emma E M; Kent, Jack W.; Curran, Joanne E.; Dyer, Thomas D.; Göring, Harald H H; Olvera, Rene L; Woolsey, Mary D.; Duggirala, Ravi; Fox, Peter T; Blangero, John; Glahn, David C.

In: Addiction, 2016.

Research output: Contribution to journalArticle

Hodgson, K, Almasy, L, Knowles, EEM, Kent, JW, Curran, JE, Dyer, TD, Göring, HHH, Olvera, RL, Woolsey, MD, Duggirala, R, Fox, PT, Blangero, J & Glahn, DC 2016, 'The genetic basis of the comorbidity between cannabis use and major depression', Addiction. https://doi.org/10.1111/add.13558
Hodgson, Karen ; Almasy, Laura ; Knowles, Emma E M ; Kent, Jack W. ; Curran, Joanne E. ; Dyer, Thomas D. ; Göring, Harald H H ; Olvera, Rene L ; Woolsey, Mary D. ; Duggirala, Ravi ; Fox, Peter T ; Blangero, John ; Glahn, David C. / The genetic basis of the comorbidity between cannabis use and major depression. In: Addiction. 2016.
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abstract = "Background and aims: 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. Design: Family-based univariate and bivariate genetic analysis. Setting: San Antonio, Texas, USA. Participants: 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. Measurements: 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. Findings: 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. Conclusions: 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.",
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T1 - The genetic basis of the comorbidity between cannabis use and major depression

AU - Hodgson, Karen

AU - Almasy, Laura

AU - Knowles, Emma E M

AU - Kent, Jack W.

AU - Curran, Joanne E.

AU - Dyer, Thomas D.

AU - Göring, Harald H H

AU - Olvera, Rene L

AU - Woolsey, Mary D.

AU - Duggirala, Ravi

AU - Fox, Peter T

AU - Blangero, John

AU - Glahn, David C.

PY - 2016

Y1 - 2016

N2 - Background and aims: 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. Design: Family-based univariate and bivariate genetic analysis. Setting: San Antonio, Texas, USA. Participants: 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. Measurements: 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. Findings: 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. Conclusions: 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.

AB - Background and aims: 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. Design: Family-based univariate and bivariate genetic analysis. Setting: San Antonio, Texas, USA. Participants: 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. Measurements: 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. Findings: 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. Conclusions: 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.

KW - Cannabis

KW - Comorbidity

KW - Genetics

KW - Linkage

KW - Major depression

KW - Pleiotropy

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