Linkage for platelet monoamine oxidase (MAO) activity

Results from a replication sample

Nancy L. Saccone, John P. Rice, Nan Rochberg, Jeff T. Williams, Alison Goate, Theodore Reich, Howard Edenberg, Tatiana Foroud, John Nurnberger, Laura J. Bierut, Raymond Crowe, Ting Kai Li

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Background: Monoamine oxidase B (MAO-B) degrades catecholamines in presynaptic nerve endings and is also active in platelets. There is evidence to suggest that platelet MAO-B activity level is controlled by a major genetic locus distinct from the structural gene on the X chromosome. To expand on a prior report, new linkage analyses for platelet MAO-B activity have been performed on the previously analyzed sample (designated the initial sample), on a new sample of families (the replication sample), and on the combined sample. These families were recruited as part of the Collaborative Study on the Genetics of Alcoholism (COGA). Methods: The initial sample consists of 105 extended families providing 1002 nonindependent (412 independent) sib pairs that have been phenotyped for MAO activity and genotyped. The replication sample of 157 extended families contains 608 nonindependent (309 independent) phenotyped and genotyped sib pairs. Analyses were conducted using Haseman-Elston based regression on sib pairs and variance component analysis on extended pedigrees, and the importance of cigarette smoking and gender as covariates of platelet MAO-B activity was taken into account. Results: Regions on chromosomes 2, 9, and 12 indicated consistent evidence for linkage across the two distinct datasets by at least one analysis method. Under Haseman-Elston regression of independent sib pairs, only the chromosome 2 region gave lod scores above 1 in both the initial and replication samples. Using all possible pairs, unweighted, for the regression, chromosome 12 gave lod scores above 1 in both samples. For variance component analysis, only the chromosome 9 region gave lod scores above 1 in both samples. Conclusions: The consistency across datasets of these findings is encouraging. In particular, variance component analysis of extended pedigrees supports a potential linkage of MAO-B activity to chromosome 9, with a lod over 3 at 115 cM near D9S261 in the combined sample. Sib-pair regression supports this finding with modest lod scores in the region. Suggestive linkage to chromosomes 2 and 12 from sib-pair analysis is only weakly supported by variance component analysis.

Original languageEnglish
Pages (from-to)603-609
Number of pages7
JournalAlcoholism: Clinical and Experimental Research
Volume26
Issue number5
StatePublished - 2002

Fingerprint

Monoamine Oxidase
Chromosomes
Platelets
Lod Score
Blood Platelets
Chromosomes, Human, Pair 12
Chromosomes, Human, Pair 9
Chromosomes, Human, Pair 2
Analysis of Variance
Pedigree
X-Linked Genes
Genetic Loci
Presynaptic Terminals
Alcoholism
Catecholamines
Tobacco Products
Smoking
Genes

Keywords

  • Linkage
  • Quantitative Trait
  • Sib-Pair Analysis
  • Smoking
  • Variance Component Analysis

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Toxicology

Cite this

Saccone, N. L., Rice, J. P., Rochberg, N., Williams, J. T., Goate, A., Reich, T., ... Li, T. K. (2002). Linkage for platelet monoamine oxidase (MAO) activity: Results from a replication sample. Alcoholism: Clinical and Experimental Research, 26(5), 603-609.

Linkage for platelet monoamine oxidase (MAO) activity : Results from a replication sample. / Saccone, Nancy L.; Rice, John P.; Rochberg, Nan; Williams, Jeff T.; Goate, Alison; Reich, Theodore; Edenberg, Howard; Foroud, Tatiana; Nurnberger, John; Bierut, Laura J.; Crowe, Raymond; Li, Ting Kai.

In: Alcoholism: Clinical and Experimental Research, Vol. 26, No. 5, 2002, p. 603-609.

Research output: Contribution to journalArticle

Saccone, NL, Rice, JP, Rochberg, N, Williams, JT, Goate, A, Reich, T, Edenberg, H, Foroud, T, Nurnberger, J, Bierut, LJ, Crowe, R & Li, TK 2002, 'Linkage for platelet monoamine oxidase (MAO) activity: Results from a replication sample', Alcoholism: Clinical and Experimental Research, vol. 26, no. 5, pp. 603-609.
Saccone NL, Rice JP, Rochberg N, Williams JT, Goate A, Reich T et al. Linkage for platelet monoamine oxidase (MAO) activity: Results from a replication sample. Alcoholism: Clinical and Experimental Research. 2002;26(5):603-609.
Saccone, Nancy L. ; Rice, John P. ; Rochberg, Nan ; Williams, Jeff T. ; Goate, Alison ; Reich, Theodore ; Edenberg, Howard ; Foroud, Tatiana ; Nurnberger, John ; Bierut, Laura J. ; Crowe, Raymond ; Li, Ting Kai. / Linkage for platelet monoamine oxidase (MAO) activity : Results from a replication sample. In: Alcoholism: Clinical and Experimental Research. 2002 ; Vol. 26, No. 5. pp. 603-609.
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abstract = "Background: Monoamine oxidase B (MAO-B) degrades catecholamines in presynaptic nerve endings and is also active in platelets. There is evidence to suggest that platelet MAO-B activity level is controlled by a major genetic locus distinct from the structural gene on the X chromosome. To expand on a prior report, new linkage analyses for platelet MAO-B activity have been performed on the previously analyzed sample (designated the initial sample), on a new sample of families (the replication sample), and on the combined sample. These families were recruited as part of the Collaborative Study on the Genetics of Alcoholism (COGA). Methods: The initial sample consists of 105 extended families providing 1002 nonindependent (412 independent) sib pairs that have been phenotyped for MAO activity and genotyped. The replication sample of 157 extended families contains 608 nonindependent (309 independent) phenotyped and genotyped sib pairs. Analyses were conducted using Haseman-Elston based regression on sib pairs and variance component analysis on extended pedigrees, and the importance of cigarette smoking and gender as covariates of platelet MAO-B activity was taken into account. Results: Regions on chromosomes 2, 9, and 12 indicated consistent evidence for linkage across the two distinct datasets by at least one analysis method. Under Haseman-Elston regression of independent sib pairs, only the chromosome 2 region gave lod scores above 1 in both the initial and replication samples. Using all possible pairs, unweighted, for the regression, chromosome 12 gave lod scores above 1 in both samples. For variance component analysis, only the chromosome 9 region gave lod scores above 1 in both samples. Conclusions: The consistency across datasets of these findings is encouraging. In particular, variance component analysis of extended pedigrees supports a potential linkage of MAO-B activity to chromosome 9, with a lod over 3 at 115 cM near D9S261 in the combined sample. Sib-pair regression supports this finding with modest lod scores in the region. Suggestive linkage to chromosomes 2 and 12 from sib-pair analysis is only weakly supported by variance component analysis.",
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AU - Saccone, Nancy L.

AU - Rice, John P.

AU - Rochberg, Nan

AU - Williams, Jeff T.

AU - Goate, Alison

AU - Reich, Theodore

AU - Edenberg, Howard

AU - Foroud, Tatiana

AU - Nurnberger, John

AU - Bierut, Laura J.

AU - Crowe, Raymond

AU - Li, Ting Kai

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N2 - Background: Monoamine oxidase B (MAO-B) degrades catecholamines in presynaptic nerve endings and is also active in platelets. There is evidence to suggest that platelet MAO-B activity level is controlled by a major genetic locus distinct from the structural gene on the X chromosome. To expand on a prior report, new linkage analyses for platelet MAO-B activity have been performed on the previously analyzed sample (designated the initial sample), on a new sample of families (the replication sample), and on the combined sample. These families were recruited as part of the Collaborative Study on the Genetics of Alcoholism (COGA). Methods: The initial sample consists of 105 extended families providing 1002 nonindependent (412 independent) sib pairs that have been phenotyped for MAO activity and genotyped. The replication sample of 157 extended families contains 608 nonindependent (309 independent) phenotyped and genotyped sib pairs. Analyses were conducted using Haseman-Elston based regression on sib pairs and variance component analysis on extended pedigrees, and the importance of cigarette smoking and gender as covariates of platelet MAO-B activity was taken into account. Results: Regions on chromosomes 2, 9, and 12 indicated consistent evidence for linkage across the two distinct datasets by at least one analysis method. Under Haseman-Elston regression of independent sib pairs, only the chromosome 2 region gave lod scores above 1 in both the initial and replication samples. Using all possible pairs, unweighted, for the regression, chromosome 12 gave lod scores above 1 in both samples. For variance component analysis, only the chromosome 9 region gave lod scores above 1 in both samples. Conclusions: The consistency across datasets of these findings is encouraging. In particular, variance component analysis of extended pedigrees supports a potential linkage of MAO-B activity to chromosome 9, with a lod over 3 at 115 cM near D9S261 in the combined sample. Sib-pair regression supports this finding with modest lod scores in the region. Suggestive linkage to chromosomes 2 and 12 from sib-pair analysis is only weakly supported by variance component analysis.

AB - Background: Monoamine oxidase B (MAO-B) degrades catecholamines in presynaptic nerve endings and is also active in platelets. There is evidence to suggest that platelet MAO-B activity level is controlled by a major genetic locus distinct from the structural gene on the X chromosome. To expand on a prior report, new linkage analyses for platelet MAO-B activity have been performed on the previously analyzed sample (designated the initial sample), on a new sample of families (the replication sample), and on the combined sample. These families were recruited as part of the Collaborative Study on the Genetics of Alcoholism (COGA). Methods: The initial sample consists of 105 extended families providing 1002 nonindependent (412 independent) sib pairs that have been phenotyped for MAO activity and genotyped. The replication sample of 157 extended families contains 608 nonindependent (309 independent) phenotyped and genotyped sib pairs. Analyses were conducted using Haseman-Elston based regression on sib pairs and variance component analysis on extended pedigrees, and the importance of cigarette smoking and gender as covariates of platelet MAO-B activity was taken into account. Results: Regions on chromosomes 2, 9, and 12 indicated consistent evidence for linkage across the two distinct datasets by at least one analysis method. Under Haseman-Elston regression of independent sib pairs, only the chromosome 2 region gave lod scores above 1 in both the initial and replication samples. Using all possible pairs, unweighted, for the regression, chromosome 12 gave lod scores above 1 in both samples. For variance component analysis, only the chromosome 9 region gave lod scores above 1 in both samples. Conclusions: The consistency across datasets of these findings is encouraging. In particular, variance component analysis of extended pedigrees supports a potential linkage of MAO-B activity to chromosome 9, with a lod over 3 at 115 cM near D9S261 in the combined sample. Sib-pair regression supports this finding with modest lod scores in the region. Suggestive linkage to chromosomes 2 and 12 from sib-pair analysis is only weakly supported by variance component analysis.

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