Linkage for platelet monoamine oxidase (MAO) activity: results from a replication sample.
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.
Saccone
Nancy L
NL
Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri 63110, USA. nlims@vodka.wustl.edu
Rice
John P
JP
Rochberg
Nan
N
Williams
Jeff T
JT
Goate
Alison
A
Reich
Theodore
T
Edenberg
Howard J
HJ
Foroud
Tatiana
T
Nurnberger
John I
JI
Bierut
Laura J
LJ
Crowe
Raymond
R
Li
Ting-Kai
TK
D001792:Blood Platelets / Q000201:enzymology*; D005260:Female; D008040:Genetic Linkage / Q000502:physiology*; D006801:Humans; D008126:Lod Score; D008297:Male; D008995:Monoamine Oxidase / Q000235:genetics* / Q000378:metabolism*; D010375:Pedigree
D008995:Monoamine Oxidase