Genome-wide linkage and follow-up association study of postpartum mood symptoms

Pamela Belmonte Mahon, Jennifer L. Payne, Dean F. MacKinnon, Francis M. Mondimore, Fernando S. Goes, Barbara Schweizer, Dubravka Jancic, William H. Coryell, Peter A. Holmans, Jianxin Shi, James A. Knowles, William A. Scheftner, Myrna M. Weissman, Douglas F. Levinson, J. Raymond DePaulo, Peter P. Zandi, James B. Potash, John R. Kelsoe, Tiffany A. Greenwood, Caroline NievergeltNicholas Schork, Erin N. Smith, Cinnamon Bloss, John Nurnberger, Howard J. Edenberg, Tatiana Foroud, John Nurnberger, Chunyu Liu, Judith A. Badner, William B. Lawson, Evaristus A. Nwulia, Maria Hipolito, William Coryell, John Rice, William Byerley, Francis McMahon, Thomas G. Schulze, Wade Berrettini, Melvin G. McInnis, Sebastian Zöllner, David Craig, Howard Edenberg

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

Objective: Family studies have suggested that postpartum mood symptoms might have a partly genetic etiology. The authors used a genome-wide linkage analysis to search for chromosomal regions that harbor genetic variants conferring susceptibility for such symptoms. The authors then fine-mapped their best linkage regions, assessing single nucleotide polymorphisms (SNPs) for genetic association with postpartum symptoms. Method: Subjects were ascertained from two studies: the NIMH Genetics Initiative Bipolar Disorder project and the Genetics of Recurrent Early-Onset Depression. Subjects included women with a history of pregnancy, any mood disorder, and information about postpartum symptoms. In the linkage study, 1,210 women met criteria (23% with postpartum symptoms), and 417 microsatellite markers were analyzed in multipoint allele sharing analyses. For the association study, 759 women met criteria (25% with postpartum symptoms), and 16,916 SNPs in the regions of the best linkage peaks were assessed for association with postpartum symptoms. Results: The maximum linkage peak for postpartum symptoms occurred on chromosome 1q21.3-q32.1, with a chromosome-wide significant likelihood ratio Z score (ZLR) of 2.93 (permutation p=0.02). This was a significant increase over the baseline Z LR of 0.32 observed at this locus among all women with a mood disorder (permutation p=0.004). Suggestive linkage was also found on 9p24.3-p22.3 (ZLR=2.91). In the fine-mapping study, the strongest implicated gene was HMCN1 (nominal p=0.00017), containing four estrogen receptor binding sites, although this was not region-wide significant. Conclusions: This is the first study to examine the genetic etiology of postpartum mood symptoms using genome-wide data. The results suggest that genetic variations on chromosomes 1q21.3-q32.1 and 9p24.3-p22.3 may increase susceptibility to postpartum mood symptoms.

Original languageEnglish
Pages (from-to)1229-1237
Number of pages9
JournalAmerican Journal of Psychiatry
Volume166
Issue number11
DOIs
StatePublished - Nov 1 2009

Fingerprint

Postpartum Period
Genome
Chromosomes
Mood Disorders
Single Nucleotide Polymorphism
National Institute of Mental Health (U.S.)
Reproductive History
Bipolar Disorder
Estrogen Receptors
Microsatellite Repeats
Alleles
Binding Sites
Depression
Genes

ASJC Scopus subject areas

  • Psychiatry and Mental health

Cite this

Mahon, P. B., Payne, J. L., MacKinnon, D. F., Mondimore, F. M., Goes, F. S., Schweizer, B., ... Edenberg, H. (2009). Genome-wide linkage and follow-up association study of postpartum mood symptoms. American Journal of Psychiatry, 166(11), 1229-1237. https://doi.org/10.1176/appi.ajp.2009.09030417

Genome-wide linkage and follow-up association study of postpartum mood symptoms. / Mahon, Pamela Belmonte; Payne, Jennifer L.; MacKinnon, Dean F.; Mondimore, Francis M.; Goes, Fernando S.; Schweizer, Barbara; Jancic, Dubravka; Coryell, William H.; Holmans, Peter A.; Shi, Jianxin; Knowles, James A.; Scheftner, William A.; Weissman, Myrna M.; Levinson, Douglas F.; DePaulo, J. Raymond; Zandi, Peter P.; Potash, James B.; Kelsoe, John R.; Greenwood, Tiffany A.; Nievergelt, Caroline; Schork, Nicholas; Smith, Erin N.; Bloss, Cinnamon; Nurnberger, John; Edenberg, Howard J.; Foroud, Tatiana; Nurnberger, John; Liu, Chunyu; Badner, Judith A.; Lawson, William B.; Nwulia, Evaristus A.; Hipolito, Maria; Coryell, William; Rice, John; Byerley, William; McMahon, Francis; Schulze, Thomas G.; Berrettini, Wade; McInnis, Melvin G.; Zöllner, Sebastian; Craig, David; Edenberg, Howard.

In: American Journal of Psychiatry, Vol. 166, No. 11, 01.11.2009, p. 1229-1237.

Research output: Contribution to journalArticle

Mahon, PB, Payne, JL, MacKinnon, DF, Mondimore, FM, Goes, FS, Schweizer, B, Jancic, D, Coryell, WH, Holmans, PA, Shi, J, Knowles, JA, Scheftner, WA, Weissman, MM, Levinson, DF, DePaulo, JR, Zandi, PP, Potash, JB, Kelsoe, JR, Greenwood, TA, Nievergelt, C, Schork, N, Smith, EN, Bloss, C, Nurnberger, J, Edenberg, HJ, Foroud, T, Nurnberger, J, Liu, C, Badner, JA, Lawson, WB, Nwulia, EA, Hipolito, M, Coryell, W, Rice, J, Byerley, W, McMahon, F, Schulze, TG, Berrettini, W, McInnis, MG, Zöllner, S, Craig, D & Edenberg, H 2009, 'Genome-wide linkage and follow-up association study of postpartum mood symptoms', American Journal of Psychiatry, vol. 166, no. 11, pp. 1229-1237. https://doi.org/10.1176/appi.ajp.2009.09030417
Mahon PB, Payne JL, MacKinnon DF, Mondimore FM, Goes FS, Schweizer B et al. Genome-wide linkage and follow-up association study of postpartum mood symptoms. American Journal of Psychiatry. 2009 Nov 1;166(11):1229-1237. https://doi.org/10.1176/appi.ajp.2009.09030417
Mahon, Pamela Belmonte ; Payne, Jennifer L. ; MacKinnon, Dean F. ; Mondimore, Francis M. ; Goes, Fernando S. ; Schweizer, Barbara ; Jancic, Dubravka ; Coryell, William H. ; Holmans, Peter A. ; Shi, Jianxin ; Knowles, James A. ; Scheftner, William A. ; Weissman, Myrna M. ; Levinson, Douglas F. ; DePaulo, J. Raymond ; Zandi, Peter P. ; Potash, James B. ; Kelsoe, John R. ; Greenwood, Tiffany A. ; Nievergelt, Caroline ; Schork, Nicholas ; Smith, Erin N. ; Bloss, Cinnamon ; Nurnberger, John ; Edenberg, Howard J. ; Foroud, Tatiana ; Nurnberger, John ; Liu, Chunyu ; Badner, Judith A. ; Lawson, William B. ; Nwulia, Evaristus A. ; Hipolito, Maria ; Coryell, William ; Rice, John ; Byerley, William ; McMahon, Francis ; Schulze, Thomas G. ; Berrettini, Wade ; McInnis, Melvin G. ; Zöllner, Sebastian ; Craig, David ; Edenberg, Howard. / Genome-wide linkage and follow-up association study of postpartum mood symptoms. In: American Journal of Psychiatry. 2009 ; Vol. 166, No. 11. pp. 1229-1237.
@article{0beff4f1eb4a4514a392e553059301ac,
title = "Genome-wide linkage and follow-up association study of postpartum mood symptoms",
abstract = "Objective: Family studies have suggested that postpartum mood symptoms might have a partly genetic etiology. The authors used a genome-wide linkage analysis to search for chromosomal regions that harbor genetic variants conferring susceptibility for such symptoms. The authors then fine-mapped their best linkage regions, assessing single nucleotide polymorphisms (SNPs) for genetic association with postpartum symptoms. Method: Subjects were ascertained from two studies: the NIMH Genetics Initiative Bipolar Disorder project and the Genetics of Recurrent Early-Onset Depression. Subjects included women with a history of pregnancy, any mood disorder, and information about postpartum symptoms. In the linkage study, 1,210 women met criteria (23{\%} with postpartum symptoms), and 417 microsatellite markers were analyzed in multipoint allele sharing analyses. For the association study, 759 women met criteria (25{\%} with postpartum symptoms), and 16,916 SNPs in the regions of the best linkage peaks were assessed for association with postpartum symptoms. Results: The maximum linkage peak for postpartum symptoms occurred on chromosome 1q21.3-q32.1, with a chromosome-wide significant likelihood ratio Z score (ZLR) of 2.93 (permutation p=0.02). This was a significant increase over the baseline Z LR of 0.32 observed at this locus among all women with a mood disorder (permutation p=0.004). Suggestive linkage was also found on 9p24.3-p22.3 (ZLR=2.91). In the fine-mapping study, the strongest implicated gene was HMCN1 (nominal p=0.00017), containing four estrogen receptor binding sites, although this was not region-wide significant. Conclusions: This is the first study to examine the genetic etiology of postpartum mood symptoms using genome-wide data. The results suggest that genetic variations on chromosomes 1q21.3-q32.1 and 9p24.3-p22.3 may increase susceptibility to postpartum mood symptoms.",
author = "Mahon, {Pamela Belmonte} and Payne, {Jennifer L.} and MacKinnon, {Dean F.} and Mondimore, {Francis M.} and Goes, {Fernando S.} and Barbara Schweizer and Dubravka Jancic and Coryell, {William H.} and Holmans, {Peter A.} and Jianxin Shi and Knowles, {James A.} and Scheftner, {William A.} and Weissman, {Myrna M.} and Levinson, {Douglas F.} and DePaulo, {J. Raymond} and Zandi, {Peter P.} and Potash, {James B.} and Kelsoe, {John R.} and Greenwood, {Tiffany A.} and Caroline Nievergelt and Nicholas Schork and Smith, {Erin N.} and Cinnamon Bloss and John Nurnberger and Edenberg, {Howard J.} and Tatiana Foroud and John Nurnberger and Chunyu Liu and Badner, {Judith A.} and Lawson, {William B.} and Nwulia, {Evaristus A.} and Maria Hipolito and William Coryell and John Rice and William Byerley and Francis McMahon and Schulze, {Thomas G.} and Wade Berrettini and McInnis, {Melvin G.} and Sebastian Z{\"o}llner and David Craig and Howard Edenberg",
year = "2009",
month = "11",
day = "1",
doi = "10.1176/appi.ajp.2009.09030417",
language = "English",
volume = "166",
pages = "1229--1237",
journal = "American Journal of Psychiatry",
issn = "0002-953X",
publisher = "American Psychiatric Association",
number = "11",

}

TY - JOUR

T1 - Genome-wide linkage and follow-up association study of postpartum mood symptoms

AU - Mahon, Pamela Belmonte

AU - Payne, Jennifer L.

AU - MacKinnon, Dean F.

AU - Mondimore, Francis M.

AU - Goes, Fernando S.

AU - Schweizer, Barbara

AU - Jancic, Dubravka

AU - Coryell, William H.

AU - Holmans, Peter A.

AU - Shi, Jianxin

AU - Knowles, James A.

AU - Scheftner, William A.

AU - Weissman, Myrna M.

AU - Levinson, Douglas F.

AU - DePaulo, J. Raymond

AU - Zandi, Peter P.

AU - Potash, James B.

AU - Kelsoe, John R.

AU - Greenwood, Tiffany A.

AU - Nievergelt, Caroline

AU - Schork, Nicholas

AU - Smith, Erin N.

AU - Bloss, Cinnamon

AU - Nurnberger, John

AU - Edenberg, Howard J.

AU - Foroud, Tatiana

AU - Nurnberger, John

AU - Liu, Chunyu

AU - Badner, Judith A.

AU - Lawson, William B.

AU - Nwulia, Evaristus A.

AU - Hipolito, Maria

AU - Coryell, William

AU - Rice, John

AU - Byerley, William

AU - McMahon, Francis

AU - Schulze, Thomas G.

AU - Berrettini, Wade

AU - McInnis, Melvin G.

AU - Zöllner, Sebastian

AU - Craig, David

AU - Edenberg, Howard

PY - 2009/11/1

Y1 - 2009/11/1

N2 - Objective: Family studies have suggested that postpartum mood symptoms might have a partly genetic etiology. The authors used a genome-wide linkage analysis to search for chromosomal regions that harbor genetic variants conferring susceptibility for such symptoms. The authors then fine-mapped their best linkage regions, assessing single nucleotide polymorphisms (SNPs) for genetic association with postpartum symptoms. Method: Subjects were ascertained from two studies: the NIMH Genetics Initiative Bipolar Disorder project and the Genetics of Recurrent Early-Onset Depression. Subjects included women with a history of pregnancy, any mood disorder, and information about postpartum symptoms. In the linkage study, 1,210 women met criteria (23% with postpartum symptoms), and 417 microsatellite markers were analyzed in multipoint allele sharing analyses. For the association study, 759 women met criteria (25% with postpartum symptoms), and 16,916 SNPs in the regions of the best linkage peaks were assessed for association with postpartum symptoms. Results: The maximum linkage peak for postpartum symptoms occurred on chromosome 1q21.3-q32.1, with a chromosome-wide significant likelihood ratio Z score (ZLR) of 2.93 (permutation p=0.02). This was a significant increase over the baseline Z LR of 0.32 observed at this locus among all women with a mood disorder (permutation p=0.004). Suggestive linkage was also found on 9p24.3-p22.3 (ZLR=2.91). In the fine-mapping study, the strongest implicated gene was HMCN1 (nominal p=0.00017), containing four estrogen receptor binding sites, although this was not region-wide significant. Conclusions: This is the first study to examine the genetic etiology of postpartum mood symptoms using genome-wide data. The results suggest that genetic variations on chromosomes 1q21.3-q32.1 and 9p24.3-p22.3 may increase susceptibility to postpartum mood symptoms.

AB - Objective: Family studies have suggested that postpartum mood symptoms might have a partly genetic etiology. The authors used a genome-wide linkage analysis to search for chromosomal regions that harbor genetic variants conferring susceptibility for such symptoms. The authors then fine-mapped their best linkage regions, assessing single nucleotide polymorphisms (SNPs) for genetic association with postpartum symptoms. Method: Subjects were ascertained from two studies: the NIMH Genetics Initiative Bipolar Disorder project and the Genetics of Recurrent Early-Onset Depression. Subjects included women with a history of pregnancy, any mood disorder, and information about postpartum symptoms. In the linkage study, 1,210 women met criteria (23% with postpartum symptoms), and 417 microsatellite markers were analyzed in multipoint allele sharing analyses. For the association study, 759 women met criteria (25% with postpartum symptoms), and 16,916 SNPs in the regions of the best linkage peaks were assessed for association with postpartum symptoms. Results: The maximum linkage peak for postpartum symptoms occurred on chromosome 1q21.3-q32.1, with a chromosome-wide significant likelihood ratio Z score (ZLR) of 2.93 (permutation p=0.02). This was a significant increase over the baseline Z LR of 0.32 observed at this locus among all women with a mood disorder (permutation p=0.004). Suggestive linkage was also found on 9p24.3-p22.3 (ZLR=2.91). In the fine-mapping study, the strongest implicated gene was HMCN1 (nominal p=0.00017), containing four estrogen receptor binding sites, although this was not region-wide significant. Conclusions: This is the first study to examine the genetic etiology of postpartum mood symptoms using genome-wide data. The results suggest that genetic variations on chromosomes 1q21.3-q32.1 and 9p24.3-p22.3 may increase susceptibility to postpartum mood symptoms.

UR - http://www.scopus.com/inward/record.url?scp=70449413455&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=70449413455&partnerID=8YFLogxK

U2 - 10.1176/appi.ajp.2009.09030417

DO - 10.1176/appi.ajp.2009.09030417

M3 - Article

C2 - 19755578

AN - SCOPUS:70449413455

VL - 166

SP - 1229

EP - 1237

JO - American Journal of Psychiatry

JF - American Journal of Psychiatry

SN - 0002-953X

IS - 11

ER -