Dense genomewide linkage scan for alcohol dependence in African Americans: significant linkage on chromosome 10.

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Authors: Gelernter, Joel; Kranzler, Henry R; Panhuysen, Carolien; Weiss, Roger D; Brady, Kathleen; Poling, James; Farrer, Lindsay
Year: 2009
Journal: Biological psychiatry
PMID: 18930185
DOI: 10.1016/j.biopsych.2008.08.036
PMCID: PMC2646253

#	Section	Preview
0	Introduction	Alcohol dependence (AD) is extremely costly to individuals and to society in the US and throughout…
1	Introduction	Genome scan linkage mapping projects have identified promising map positions for AD susceptibility…
2	Introduction	Until recently the only genes established to affect risk for AD were those encoding several alcohol…
3	Introduction	We collected a set of small nuclear pedigrees suitable for linkage analyses of cocaine dependence…
4	Methods	Subjects for this study were recruited at four sites: Yale University School of Medicine (APT…
5	Methods	analyses were 1408 SNPs from the genomewide scan. The program implements a model-based clustering…
6	Methods	mostly mixed-ethnicity families, clustered near the middle. The threshold we used in those cases was…
7	Diagnosis	Subjects were interviewed using the SSADDA for psychiatric diagnosis as described previously (23,…
8	Laboratory Methods	In most cases DNA was obtained from immortalized cell lines, although for some subjects DNA was…
9	Statistical Analysis	PREST (30) was used to validate the reported family relationship assignments and PedCheck (310) was…
10	Statistical Analysis	(total dataset including EA subjects who were not included in the linkage analysis) had ≤1%…
11	Statistical Analysis	in the cluster. In the few instances of an obligate recombination among SNPs in a cluster, genotypes…
12	Statistical Analysis	Multipoint nonparametric linkage analysis was then performed using the haplotypes based on the SNPs…
13	Statistical Analysis	To estimate the type I error rate in the analysis, 1000 unlinked genome scans were simulated and…
14	Results — Simulations	From 1000 genomewide simulations (for model-free multipoint linkage), we observed 1166 lod scores…
15	Results — Linkage analysis	We observed one linkage peak that satisfied empirical genomewide significance criteria (i.e., based…
16	Results — Linkage analysis	Linkage results are summarized in Table 2.
17	Discussion	We completed a dense SNP genomewide linkage scan for the trait of DSM-IV AD in a sample of AA small…
18	Discussion	These investigators observed a lod score of 4.17 at 92 cM. Because this location is not within the…
19	Discussion	Two previous linkage studies reported evidence for linkage of traits related to alcohol dependence…

Name	Type
1000 genomewide simulations local	cohort
AA	cohort
AA control subjects local	cohort
AA families	cohort
AA sample	cohort
AA small nuclear families local	cohort
AD AAs local	cohort
ADH	gene
ADH1B	gene
affected sibling pair local	cohort
African American	cohort
African-Americans	cohort
alcohol	phenotype
alcohol abuse	phenotype
alcohol dependence	phenotype
Alcohol Problems	phenotype
alcohol sensitivity	phenotype
Alcohol Use	phenotype
alcohol withdrawal	phenotype
ALDH2	gene
Alzheimer's disease	phenotype
ASPs local	cohort
Black Hispanic local	cohort
blood	drug
chr10:117.4cM local	variant
chr10:92cM local	variant
chr17:locus local	variant
CHRM2	gene
CIDR	cohort
cocaine	phenotype
cocaine-induced paranoia	phenotype
conduct disorder	phenotype
DSM-IV alcohol dependence	phenotype
EA participants	cohort
EAs	cohort
European ancestry	cohort
European population	cohort
Fagerström Test for Nicotine Dependence	phenotype
Fagerstrom Test for Nicotine Dependence scores local	phenotype
GABRA2	gene
Htr7	gene
Illumina Linkage IVb Marker Panel local	drug
Irish families local	cohort
low-level response to alcohol local	phenotype
major psychotic illness local	phenotype
Major psychotic illness local	phenotype
McLean Hospital	cohort
Medical University of South Carolina	cohort
Mission Indians local	cohort
nicotine	drug
nicotine dependence	phenotype
Nicotine dependence-related traits local	phenotype
opioid	drug
opioid dependence	phenotype
Pedcheck	drug
PREST local	drug
rs2066702	variant
saliva	drug
schizoaffective disorder	phenotype
schizophrenia	phenotype
SLC18A2	gene
small nuclear pedigrees local	cohort
SNP	cohort
study cohort	cohort
substance use	phenotype
University of Connecticut Health Center	cohort
White Hispanic local	cohort
Yale University School of Medicine	cohort

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Dense genomewide linkage scan for alcohol dependence in African Americans: significant linkage on chromosome 10.

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