Autosomal linkage scan for loci predisposing to comorbid dependence on multiple substances.

paper Cited Public

Authors: Yang, Bao-Zhu; Han, Shizhong; Kranzler, Henry R; Farrer, Lindsay A; Elston, Robert C; Gelernter, Joel
Year: 2012
Journal: American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics
PMID: 22354695
DOI: 10.1002/ajmg.b.32037
PMCID: PMC3920832

#	Section	Preview
0	INTRODUCTION	Substance dependence (SD) is a chronic psychiatric illness [Leshner, 1997; McLellan et al., 2000].…
1	INTRODUCTION	Research from adoption, twin and family studies has shown that there is a genetic diathesis in the…
2	INTRODUCTION	Current evidence suggests that copy number variants (CNVs) and rare single-nucleotide polymorphisms…
3	INTRODUCTION	Prior linkage studies have identified genomic susceptibility regions for single SD diagnoses…
4	MATERIALS AND METHODS — Recruitment	Study subjects were recruited at four recruitment sites including University of Connecticut Health…
5	MATERIALS AND METHODS — Recruitment	a major psychotic disorder (e.g., schizophrenia or schizoaffective disorder) were excluded from the…
6	MATERIALS AND METHODS — Diagnosis and Study Subjects	We interviewed and assessed subjects using the Semi-structured Assessment for Drug Dependence and…
7	MATERIALS AND METHODS — Genotyping and Quality Control	For most subjects, we obtained DNA from immortalized cell lines, but for a small proportion of the…
8	MATERIALS AND METHODS — Genotyping and Quality Control	2007] using a set of unrelated subjects (355 EA and 384 AA subjects were randomly selected, one per…
9	MATERIALS AND METHODS — Genotyping and Quality Control	In total, 1,366 (1360), 322 (70), and 46 (40) SNPs failed to pass the quality control including the…
10	MATERIALS AND METHODS — Population Assignment by Individual Genetic Profile	Populations with cryptic genetic clusters could contribute differential linkage signals [Lewis et…
11	MATERIALS AND METHODS — Fuzzy Clustering Analysis	We used fuzzy clustering analysis [Kaufman and Rousseeuw, 1990] to reduce the phenotype dimensions…
12	MATERIALS AND METHODS — Fuzzy Clustering Analysis	analysis has the advantage of providing correlated data structures that are drawn from inherent…
13	MATERIALS AND METHODS — Linkage Analyses	Linkage analyses were carried out using the model-free regression method implemented in…
14	MATERIALS AND METHODS — Linkage Analyses	Empirical thresholds for autosome-wide suggestive and significant linkages were determined by Monte…
15	MATERIALS AND METHODS — Linkage Analyses	the 1,000th highest lod score out of 22,000 lod scores for each of the 22 autosomal chromosomes from…
16	RESULTS — Comorbidity of MSD and the Fuzzy Clustering Analysis	The rate of affection with multiple forms of substance dependence was high among the family members…
17	RESULTS — Comorbidity of MSD and the Fuzzy Clustering Analysis	The fanny algorithm, with the number of clusters pre-selected to be two, resulted in two average…
18	RESULTS — Linkage Analysis of the Fuzzy Clustering Membership Coefficients	Results are summarized in Table II. In EAs, we detected a genome-wide significant linkage signal in…
19	DISCUSSION	In this linkage scan we identified several loci predisposing to comorbid dependence on multiple…

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