Genetic association of bipolar disorder with the β3 nicotinic receptor subunit gene

Sarah M. Hartz, Peng Lin, Howard Edenberg, Xiaoling Xuei, Nanette Rochberg, Scott Saccone, Wade Berrettini, Elliot Nelson, John Nurnberger, Laura J. Bierut, John P. Rice, Marvin J. Miller, Elizabeth S. Bowman, N. Leela Rau, P. Ryan Moe, Nalini Samavedy, Rif El-Mallakh, Husseini Manji, Debra A. Glitz, Eric T. MeyerCarrie Smiley, Tatiana Foroud, Leah Flury, Danielle M. Dick, Theodore Reich, Allison Goate, Melvin McInnis, J. Raymond DePaulo, Dean F. MacKinnon, Francis M. Mondimore, James B. Potash, Peter P. Zandi, Dimitrios Avramopoulos, Jennifer Payne, William Byerley, Sophia Vinogradov, William Coryell, Raymond Crowe, Elliot Gershon, Judith Badner, Francis McMahon, Chunyu Liu, Alan Sanders, Maria Caserta, Steven Dinwiddie, Tu Nguyen, Donna Harakal, John Kelsoe, Rebecca McKinney, William Scheftner, Howard M. Kravitz, Diana Marta, Annette Vaughn-Brown, Laurie Bederow, Francis J. McMahon, Layla Kassem, Sevilla Detera-Wadleigh, Lisa Austin, Dennis L. Murphy, William B. Lawson, Evarista Nwulia, Maria Hipolito

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

OBJECTIVE: Owing to the clinical relationship between bipolar disorder and nicotine dependence, we investigated two research questions: (i) are genetic associations with nicotine dependence different in individuals with bipolar disorder as compared with individuals without bipolar disorder, and (ii) do loci earlier associated with nicotine dependence have pleiotropic effects on these two diseases. METHOD: Our study consisted of 916 cases with bipolar disorder and 1028 controls. On the basis of known associations with nicotine dependence, we genotyped eight single-nucleotide polymorphisms (SNPs) on chromosome 8 (three bins) in the regions of CHRNB3 and CHRNA6, and six SNPs on chromosome 15 (three bins) in the regions of CHRNA5 and CHRNA3. RESULTS: To determine whether the genetic associations with nicotine dependence are different in bipolar disorder than in the general population, we compared allele frequencies of candidate SNPs between individuals with nicotine dependence only and individuals with both nicotine dependence and bipolar disorder. There were no statistical differences between these frequencies, indicating that genetic association with nicotine dependence is similar in individuals with bipolar disorder as in the general population. In the investigation of pleiotropic effects of these SNPs on bipolar disorder, two highly correlated synonymous SNPs in CHRNB3, rs4952 and rs4953, were significantly associated with bipolar disorder (odds ratio 1.7, 95% confidence interval: 1.2-2.4, P=0.001). This association remained significant both after adjusting for a smoking covariate and analyzing the association in nonsmokers only. CONCLUSION: Our results suggest that (i) bipolar disorder does not modify the association between nicotine dependence and nicotinic receptor subunit genes, and (ii) variants in CHRNB3/CHRNA6 are independently associated with bipolar disorder.

Original languageEnglish
Pages (from-to)77-84
Number of pages8
JournalPsychiatric Genetics
Volume21
Issue number2
DOIs
StatePublished - Apr 2011

Fingerprint

Nicotinic Receptors
Tobacco Use Disorder
Bipolar Disorder
Genes
Single Nucleotide Polymorphism
Chromosomes, Human, Pair 15
Chromosomes, Human, Pair 8
Gene Frequency
Population
Smoking
Odds Ratio
Confidence Intervals

Keywords

  • analyses
  • CHRNA3
  • CHRNA5
  • CHRNA6
  • genetic association
  • nicotine
  • tobacco use disorder

ASJC Scopus subject areas

  • Genetics(clinical)
  • Psychiatry and Mental health
  • Genetics
  • Biological Psychiatry

Cite this

Genetic association of bipolar disorder with the β3 nicotinic receptor subunit gene. / Hartz, Sarah M.; Lin, Peng; Edenberg, Howard; Xuei, Xiaoling; Rochberg, Nanette; Saccone, Scott; Berrettini, Wade; Nelson, Elliot; Nurnberger, John; Bierut, Laura J.; Rice, John P.; Miller, Marvin J.; Bowman, Elizabeth S.; Rau, N. Leela; Moe, P. Ryan; Samavedy, Nalini; El-Mallakh, Rif; Manji, Husseini; Glitz, Debra A.; Meyer, Eric T.; Smiley, Carrie; Foroud, Tatiana; Flury, Leah; Dick, Danielle M.; Reich, Theodore; Goate, Allison; McInnis, Melvin; DePaulo, J. Raymond; MacKinnon, Dean F.; Mondimore, Francis M.; Potash, James B.; Zandi, Peter P.; Avramopoulos, Dimitrios; Payne, Jennifer; Byerley, William; Vinogradov, Sophia; Coryell, William; Crowe, Raymond; Gershon, Elliot; Badner, Judith; McMahon, Francis; Liu, Chunyu; Sanders, Alan; Caserta, Maria; Dinwiddie, Steven; Nguyen, Tu; Harakal, Donna; Kelsoe, John; McKinney, Rebecca; Scheftner, William; Kravitz, Howard M.; Marta, Diana; Vaughn-Brown, Annette; Bederow, Laurie; McMahon, Francis J.; Kassem, Layla; Detera-Wadleigh, Sevilla; Austin, Lisa; Murphy, Dennis L.; Lawson, William B.; Nwulia, Evarista; Hipolito, Maria.

In: Psychiatric Genetics, Vol. 21, No. 2, 04.2011, p. 77-84.

Research output: Contribution to journalArticle

Hartz, SM, Lin, P, Edenberg, H, Xuei, X, Rochberg, N, Saccone, S, Berrettini, W, Nelson, E, Nurnberger, J, Bierut, LJ, Rice, JP, Miller, MJ, Bowman, ES, Rau, NL, Moe, PR, Samavedy, N, El-Mallakh, R, Manji, H, Glitz, DA, Meyer, ET, Smiley, C, Foroud, T, Flury, L, Dick, DM, Reich, T, Goate, A, McInnis, M, DePaulo, JR, MacKinnon, DF, Mondimore, FM, Potash, JB, Zandi, PP, Avramopoulos, D, Payne, J, Byerley, W, Vinogradov, S, Coryell, W, Crowe, R, Gershon, E, Badner, J, McMahon, F, Liu, C, Sanders, A, Caserta, M, Dinwiddie, S, Nguyen, T, Harakal, D, Kelsoe, J, McKinney, R, Scheftner, W, Kravitz, HM, Marta, D, Vaughn-Brown, A, Bederow, L, McMahon, FJ, Kassem, L, Detera-Wadleigh, S, Austin, L, Murphy, DL, Lawson, WB, Nwulia, E & Hipolito, M 2011, 'Genetic association of bipolar disorder with the β3 nicotinic receptor subunit gene', Psychiatric Genetics, vol. 21, no. 2, pp. 77-84. https://doi.org/10.1097/YPG.0b013e32834135eb
Hartz, Sarah M. ; Lin, Peng ; Edenberg, Howard ; Xuei, Xiaoling ; Rochberg, Nanette ; Saccone, Scott ; Berrettini, Wade ; Nelson, Elliot ; Nurnberger, John ; Bierut, Laura J. ; Rice, John P. ; Miller, Marvin J. ; Bowman, Elizabeth S. ; Rau, N. Leela ; Moe, P. Ryan ; Samavedy, Nalini ; El-Mallakh, Rif ; Manji, Husseini ; Glitz, Debra A. ; Meyer, Eric T. ; Smiley, Carrie ; Foroud, Tatiana ; Flury, Leah ; Dick, Danielle M. ; Reich, Theodore ; Goate, Allison ; McInnis, Melvin ; DePaulo, J. Raymond ; MacKinnon, Dean F. ; Mondimore, Francis M. ; Potash, James B. ; Zandi, Peter P. ; Avramopoulos, Dimitrios ; Payne, Jennifer ; Byerley, William ; Vinogradov, Sophia ; Coryell, William ; Crowe, Raymond ; Gershon, Elliot ; Badner, Judith ; McMahon, Francis ; Liu, Chunyu ; Sanders, Alan ; Caserta, Maria ; Dinwiddie, Steven ; Nguyen, Tu ; Harakal, Donna ; Kelsoe, John ; McKinney, Rebecca ; Scheftner, William ; Kravitz, Howard M. ; Marta, Diana ; Vaughn-Brown, Annette ; Bederow, Laurie ; McMahon, Francis J. ; Kassem, Layla ; Detera-Wadleigh, Sevilla ; Austin, Lisa ; Murphy, Dennis L. ; Lawson, William B. ; Nwulia, Evarista ; Hipolito, Maria. / Genetic association of bipolar disorder with the β3 nicotinic receptor subunit gene. In: Psychiatric Genetics. 2011 ; Vol. 21, No. 2. pp. 77-84.
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abstract = "OBJECTIVE: Owing to the clinical relationship between bipolar disorder and nicotine dependence, we investigated two research questions: (i) are genetic associations with nicotine dependence different in individuals with bipolar disorder as compared with individuals without bipolar disorder, and (ii) do loci earlier associated with nicotine dependence have pleiotropic effects on these two diseases. METHOD: Our study consisted of 916 cases with bipolar disorder and 1028 controls. On the basis of known associations with nicotine dependence, we genotyped eight single-nucleotide polymorphisms (SNPs) on chromosome 8 (three bins) in the regions of CHRNB3 and CHRNA6, and six SNPs on chromosome 15 (three bins) in the regions of CHRNA5 and CHRNA3. RESULTS: To determine whether the genetic associations with nicotine dependence are different in bipolar disorder than in the general population, we compared allele frequencies of candidate SNPs between individuals with nicotine dependence only and individuals with both nicotine dependence and bipolar disorder. There were no statistical differences between these frequencies, indicating that genetic association with nicotine dependence is similar in individuals with bipolar disorder as in the general population. In the investigation of pleiotropic effects of these SNPs on bipolar disorder, two highly correlated synonymous SNPs in CHRNB3, rs4952 and rs4953, were significantly associated with bipolar disorder (odds ratio 1.7, 95{\%} confidence interval: 1.2-2.4, P=0.001). This association remained significant both after adjusting for a smoking covariate and analyzing the association in nonsmokers only. CONCLUSION: Our results suggest that (i) bipolar disorder does not modify the association between nicotine dependence and nicotinic receptor subunit genes, and (ii) variants in CHRNB3/CHRNA6 are independently associated with bipolar disorder.",
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T1 - Genetic association of bipolar disorder with the β3 nicotinic receptor subunit gene

AU - Hartz, Sarah M.

AU - Lin, Peng

AU - Edenberg, Howard

AU - Xuei, Xiaoling

AU - Rochberg, Nanette

AU - Saccone, Scott

AU - Berrettini, Wade

AU - Nelson, Elliot

AU - Nurnberger, John

AU - Bierut, Laura J.

AU - Rice, John P.

AU - Miller, Marvin J.

AU - Bowman, Elizabeth S.

AU - Rau, N. Leela

AU - Moe, P. Ryan

AU - Samavedy, Nalini

AU - El-Mallakh, Rif

AU - Manji, Husseini

AU - Glitz, Debra A.

AU - Meyer, Eric T.

AU - Smiley, Carrie

AU - Foroud, Tatiana

AU - Flury, Leah

AU - Dick, Danielle M.

AU - Reich, Theodore

AU - Goate, Allison

AU - McInnis, Melvin

AU - DePaulo, J. Raymond

AU - MacKinnon, Dean F.

AU - Mondimore, Francis M.

AU - Potash, James B.

AU - Zandi, Peter P.

AU - Avramopoulos, Dimitrios

AU - Payne, Jennifer

AU - Byerley, William

AU - Vinogradov, Sophia

AU - Coryell, William

AU - Crowe, Raymond

AU - Gershon, Elliot

AU - Badner, Judith

AU - McMahon, Francis

AU - Liu, Chunyu

AU - Sanders, Alan

AU - Caserta, Maria

AU - Dinwiddie, Steven

AU - Nguyen, Tu

AU - Harakal, Donna

AU - Kelsoe, John

AU - McKinney, Rebecca

AU - Scheftner, William

AU - Kravitz, Howard M.

AU - Marta, Diana

AU - Vaughn-Brown, Annette

AU - Bederow, Laurie

AU - McMahon, Francis J.

AU - Kassem, Layla

AU - Detera-Wadleigh, Sevilla

AU - Austin, Lisa

AU - Murphy, Dennis L.

AU - Lawson, William B.

AU - Nwulia, Evarista

AU - Hipolito, Maria

PY - 2011/4

Y1 - 2011/4

N2 - OBJECTIVE: Owing to the clinical relationship between bipolar disorder and nicotine dependence, we investigated two research questions: (i) are genetic associations with nicotine dependence different in individuals with bipolar disorder as compared with individuals without bipolar disorder, and (ii) do loci earlier associated with nicotine dependence have pleiotropic effects on these two diseases. METHOD: Our study consisted of 916 cases with bipolar disorder and 1028 controls. On the basis of known associations with nicotine dependence, we genotyped eight single-nucleotide polymorphisms (SNPs) on chromosome 8 (three bins) in the regions of CHRNB3 and CHRNA6, and six SNPs on chromosome 15 (three bins) in the regions of CHRNA5 and CHRNA3. RESULTS: To determine whether the genetic associations with nicotine dependence are different in bipolar disorder than in the general population, we compared allele frequencies of candidate SNPs between individuals with nicotine dependence only and individuals with both nicotine dependence and bipolar disorder. There were no statistical differences between these frequencies, indicating that genetic association with nicotine dependence is similar in individuals with bipolar disorder as in the general population. In the investigation of pleiotropic effects of these SNPs on bipolar disorder, two highly correlated synonymous SNPs in CHRNB3, rs4952 and rs4953, were significantly associated with bipolar disorder (odds ratio 1.7, 95% confidence interval: 1.2-2.4, P=0.001). This association remained significant both after adjusting for a smoking covariate and analyzing the association in nonsmokers only. CONCLUSION: Our results suggest that (i) bipolar disorder does not modify the association between nicotine dependence and nicotinic receptor subunit genes, and (ii) variants in CHRNB3/CHRNA6 are independently associated with bipolar disorder.

AB - OBJECTIVE: Owing to the clinical relationship between bipolar disorder and nicotine dependence, we investigated two research questions: (i) are genetic associations with nicotine dependence different in individuals with bipolar disorder as compared with individuals without bipolar disorder, and (ii) do loci earlier associated with nicotine dependence have pleiotropic effects on these two diseases. METHOD: Our study consisted of 916 cases with bipolar disorder and 1028 controls. On the basis of known associations with nicotine dependence, we genotyped eight single-nucleotide polymorphisms (SNPs) on chromosome 8 (three bins) in the regions of CHRNB3 and CHRNA6, and six SNPs on chromosome 15 (three bins) in the regions of CHRNA5 and CHRNA3. RESULTS: To determine whether the genetic associations with nicotine dependence are different in bipolar disorder than in the general population, we compared allele frequencies of candidate SNPs between individuals with nicotine dependence only and individuals with both nicotine dependence and bipolar disorder. There were no statistical differences between these frequencies, indicating that genetic association with nicotine dependence is similar in individuals with bipolar disorder as in the general population. In the investigation of pleiotropic effects of these SNPs on bipolar disorder, two highly correlated synonymous SNPs in CHRNB3, rs4952 and rs4953, were significantly associated with bipolar disorder (odds ratio 1.7, 95% confidence interval: 1.2-2.4, P=0.001). This association remained significant both after adjusting for a smoking covariate and analyzing the association in nonsmokers only. CONCLUSION: Our results suggest that (i) bipolar disorder does not modify the association between nicotine dependence and nicotinic receptor subunit genes, and (ii) variants in CHRNB3/CHRNA6 are independently associated with bipolar disorder.

KW - analyses

KW - CHRNA3

KW - CHRNA5

KW - CHRNA6

KW - genetic association

KW - nicotine

KW - tobacco use disorder

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