Genetics of recurrent early-onset major depression (GenRED)

Significant linkage on chromosome 15q25-q26 after fine mapping with single nucleotide polymorphism markers

Douglas F. Levinson, Oleg V. Evgrafov, James A. Knowles, James Bennett Potash, Myrna M. Weissman, William A. Scheftner, J Raymond Depaulo, Raymond R. Crowe, Kathleen Murphy-Eberenz, Diana H. Marta, Melvin G. McInnis, Philip Adams, Madeline Gladis, Erin B. Miller, Jo Thomas, Peter Holmans

Research output: Contribution to journalArticle

Abstract

Objective: The authors studied a dense map of single nucleotide polymorphism (SNP) DNA markers on chromosome 15q25-q26 to maximize the informativeness of genetic linkage analyses in a region where they previously reported suggestive evidence for linkage of recurrent early-onset major depressive disorder. Method: In 631 European-ancestry families with multiple cases of recurrent early-onset major depressive disorder, 88 SNPs were genotyped, and multipoint allele-sharing linkage analyses were carried out. Marker-marker linkage disequilibrium was minimized, and a simulation study with founder haplotypes from these families suggested that linkage scores were not inflated by linkage disequilibrium. Results: The dense SNP map increased the information content of the analysis from around 0.7 to over 0.9. The maximum evidence for linkage was the Z likelihood ratio score statistic of Kong and Cox (ZLR)=4.69 at 109.8 cM. The exact p value was below the genomewide significance threshold. By contrast, in the genome scan with microsatellite markers at 9 cM spacing, the maximum ZLR for European-ancestry families was 3.43 (106.53 cM). It was estimated that the linked locus or loci in this region might account for a 20% or less populationwide increase in risk to siblings of cases. Conclusions: This region has produced modestly positive evidence for linkage to depression and related traits in other studies. These results suggest that DNA sequence variations in one or more genes in the 15q25-q26 region can increase susceptibility to major depression and that efforts are warranted to identify these genes.

Original languageEnglish (US)
Pages (from-to)259-264
Number of pages6
JournalAmerican Journal of Psychiatry
Volume164
Issue number2
DOIs
StatePublished - Feb 2007
Externally publishedYes

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Single Nucleotide Polymorphism
Chromosomes
Linkage Disequilibrium
Major Depressive Disorder
Depression
Genetic Linkage
Genetic Markers
Microsatellite Repeats
Haplotypes
Genes
Alleles
Genome

ASJC Scopus subject areas

  • Psychiatry and Mental health

Cite this

Genetics of recurrent early-onset major depression (GenRED) : Significant linkage on chromosome 15q25-q26 after fine mapping with single nucleotide polymorphism markers. / Levinson, Douglas F.; Evgrafov, Oleg V.; Knowles, James A.; Potash, James Bennett; Weissman, Myrna M.; Scheftner, William A.; Depaulo, J Raymond; Crowe, Raymond R.; Murphy-Eberenz, Kathleen; Marta, Diana H.; McInnis, Melvin G.; Adams, Philip; Gladis, Madeline; Miller, Erin B.; Thomas, Jo; Holmans, Peter.

In: American Journal of Psychiatry, Vol. 164, No. 2, 02.2007, p. 259-264.

Research output: Contribution to journalArticle

Levinson, DF, Evgrafov, OV, Knowles, JA, Potash, JB, Weissman, MM, Scheftner, WA, Depaulo, JR, Crowe, RR, Murphy-Eberenz, K, Marta, DH, McInnis, MG, Adams, P, Gladis, M, Miller, EB, Thomas, J & Holmans, P 2007, 'Genetics of recurrent early-onset major depression (GenRED): Significant linkage on chromosome 15q25-q26 after fine mapping with single nucleotide polymorphism markers', American Journal of Psychiatry, vol. 164, no. 2, pp. 259-264. https://doi.org/10.1176/appi.ajp.164.2.259
Levinson, Douglas F. ; Evgrafov, Oleg V. ; Knowles, James A. ; Potash, James Bennett ; Weissman, Myrna M. ; Scheftner, William A. ; Depaulo, J Raymond ; Crowe, Raymond R. ; Murphy-Eberenz, Kathleen ; Marta, Diana H. ; McInnis, Melvin G. ; Adams, Philip ; Gladis, Madeline ; Miller, Erin B. ; Thomas, Jo ; Holmans, Peter. / Genetics of recurrent early-onset major depression (GenRED) : Significant linkage on chromosome 15q25-q26 after fine mapping with single nucleotide polymorphism markers. In: American Journal of Psychiatry. 2007 ; Vol. 164, No. 2. pp. 259-264.
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abstract = "Objective: The authors studied a dense map of single nucleotide polymorphism (SNP) DNA markers on chromosome 15q25-q26 to maximize the informativeness of genetic linkage analyses in a region where they previously reported suggestive evidence for linkage of recurrent early-onset major depressive disorder. Method: In 631 European-ancestry families with multiple cases of recurrent early-onset major depressive disorder, 88 SNPs were genotyped, and multipoint allele-sharing linkage analyses were carried out. Marker-marker linkage disequilibrium was minimized, and a simulation study with founder haplotypes from these families suggested that linkage scores were not inflated by linkage disequilibrium. Results: The dense SNP map increased the information content of the analysis from around 0.7 to over 0.9. The maximum evidence for linkage was the Z likelihood ratio score statistic of Kong and Cox (ZLR)=4.69 at 109.8 cM. The exact p value was below the genomewide significance threshold. By contrast, in the genome scan with microsatellite markers at 9 cM spacing, the maximum ZLR for European-ancestry families was 3.43 (106.53 cM). It was estimated that the linked locus or loci in this region might account for a 20{\%} or less populationwide increase in risk to siblings of cases. Conclusions: This region has produced modestly positive evidence for linkage to depression and related traits in other studies. These results suggest that DNA sequence variations in one or more genes in the 15q25-q26 region can increase susceptibility to major depression and that efforts are warranted to identify these genes.",
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T2 - Significant linkage on chromosome 15q25-q26 after fine mapping with single nucleotide polymorphism markers

AU - Levinson, Douglas F.

AU - Evgrafov, Oleg V.

AU - Knowles, James A.

AU - Potash, James Bennett

AU - Weissman, Myrna M.

AU - Scheftner, William A.

AU - Depaulo, J Raymond

AU - Crowe, Raymond R.

AU - Murphy-Eberenz, Kathleen

AU - Marta, Diana H.

AU - McInnis, Melvin G.

AU - Adams, Philip

AU - Gladis, Madeline

AU - Miller, Erin B.

AU - Thomas, Jo

AU - Holmans, Peter

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