NDLI: Ordered subset linkage analysis based on admixture proportion identifies new linkage evidence for alcohol dependence in African-Americans

Content Provider	Springer Nature Link
Author	Han, Shizhong Gelernter, Joel Kranzler, Henry R. Yang, Bao Zhu
Copyright Year	2012
Abstract	Genetic heterogeneity could reduce the power of linkage analysis to detect risk loci for complex traits such as alcohol dependence (AD). Previously, we performed a genomewide linkage analysis for AD in African-Americans (AAs) (Biol Psychiatry 65:111–115, 2009). The power of that linkage analysis could have been reduced by the presence of genetic heterogeneity owing to differences in admixture among AA families. We hypothesized that by examining a study sample whose genetic ancestry was more homogeneous, we could increase the power to detect linkage. To test this hypothesis, we performed ordered subset linkage analysis in 384 AA families using admixture proportion as a covariate to identify a more homogeneous subset of families and determine whether there is increased evidence for linkage with AD. Statistically significant increases in lod scores in subsets relative to the overall sample were identified on chromosomes 4 (P = 0.0001), 12 (P = 0.021), 15 (P = 0.026) and 22 (P = 0.0069). In a subset of 44 families with African ancestry proportions ranging from 0.858 to 0.996, we observed a genomewide significant linkage at 180 cM on chromosome 4 (lod = 4.24, pointwise P < 0.00001, empirical genomewide P = 0.008). A promising candidate gene located there, GLRA3, which encodes a subunit of the glycine neurotransmitter receptor. Our results demonstrate that admixture proportion can be used as a covariate to reduce genetic heterogeneity and enhance the detection of linkage for AD in an admixed population such as AAs. This approach could be applied to any linkage analysis for complex traits conducted in an admixed population.
Starting Page	397
Ending Page	403
Page Count	7
File Format	PDF
ISSN	03406717
Journal	Human Genetics
Volume Number	132
Issue Number	4
e-ISSN	14321203
Language	English
Publisher	Springer-Verlag
Publisher Date	2012-12-13
Publisher Place	Berlin, Heidelberg
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Human Genetics Molecular Medicine Gene Function Metabolic Diseases
Content Type	Text
Resource Type	Article
Subject	Genetics Genetics (clinical)

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