Copy number variations in 6q14.1 and 5q13.2 are associated with alcohol dependence.

paper Primary Public

Authors: Lin, Peng; Hartz, Sarah M; Wang, Jen-Chyong; Agrawal, Arpana; Zhang, Tian-Xiao; McKenna, Nicholas; Bucholz, Kathleen; Brooks, Andrew I; Tischfield, Jay A; Edenberg, Howard J; Hesselbrock, Victor M; Kramer, John R; Kuperman, Samuel; Schuckit, Marc A; Goate, Alison M; Bierut, Laura J; Rice, John P; COGA Collaborators; COGEND Collaborators, GENEVA
Year: 2012
Journal: Alcoholism, clinical and experimental research
PMID: 22702843
DOI: 10.1111/j.1530-0277.2012.01758.x
PMCID: PMC3436997

#	Section	Preview
0	Introduction	During 2001–2005, excessive alcohol use contributed to about 79,000 deaths and 2.3 million years…
1	Introduction	There is robust evidence for heritable influences on the liability to alcohol dependence (Bierut et…
2	Introduction	CNVs are duplications or deletions of a particular segment of an individual’s genome and reflect…
3	Introduction	identified (or “called”) using GWAS data where a series of single nucleotide polymorphisms…
4	Introduction	Other challenges of CNV detection include (a) size of the CNV, with smaller CNVs (<10 kb) being…
5	Introduction	There continues to be a great deal of progress in statistical methods for CNV detection. In tandem,…
6	Materials and methods — Samples	Data were drawn from the Study of Addiction: Genetics and Environment (SAGE) (Bierut et al.). SAGE…
7	Materials and methods — Samples	criteria, during their lifetime, for alcohol dependence. Note that even though the parent projects…
8	Materials and methods — Samples	Measures: A lifetime diagnosis of DSM-IV alcohol dependence was determined via self-reported…
9	Materials and methods — Samples — Genotyping and quality control	The Center for Inherited Disease Research (CIDR) at Johns Hopkins University genotyped all samples…
10	Materials and methods — Samples — CNV calling	The Illumina 1M array has a total of 1,072,820 probes, predominantly indexed by polymorphic SNPs.…
11	Materials and methods — Samples — Comparative statistics	The CNV calls from different programs were compared against each other. In our previous work, we…
12	Materials and methods — Samples — Association analysis	Logistic regressions were performed on all CNV regions. After identifying potential regions,…
13	Materials and methods — Samples — CNVs with different starting and ending point	Even when all three programs detect a CNV, they often report different starting and ending points…
14	Materials and methods — Samples — CNVs with different starting and ending point	B C, D, E, F and G by three different programs, then the results from the three programs for each…
15	Materials and methods — Samples — Validation	CNVs identified by 3 independent programs were validated in subjects carrying the variant with…
16	Results — Socio-demographic characteristics	Of the 2,583 non-Hispanic European American samples from SAGE, 95 failed to pass quality control for…
17	Results — Alcohol history	Cases also reported an earlier age of heavy and regular alcohol use, and, by definition, reported…
18	Results — CNV detection	Of the samples that passed quality control, we identified 1,139 CNV regions with length greater than…
19	Results — Association between CNVs and Alcohol Dependence	Two CNV regions were significantly associated with alcohol dependence (Table 3): chromosome 6q14.1…

Name	Type
5q13.2 local	variant
6q14.1 local	variant
alcohol	phenotype
alcohol dependence	phenotype
autism	phenotype
bipolar disorder	phenotype
case control study local	cohort
cases	cohort
Center for Inherited Disease Research	cohort
central nervous system	anatomy
Charcot-Marie-Tooth neuropathy Type 1A local	phenotype
Chr5:69,916,523-70,373,564 local	variant
Chr5:69916523-70373564 local	variant
Chr6:79,034,386-79,090,197 local	variant
Chr6:79034386-79090197 local	variant
chromosome 5q13.2 local	variant
chromosome 6q14.1 local	variant
CNV	variant
CNV deletion 5q13.2 local	variant
CNV deletion 6q14.1 local	variant
CNV duplication 5q13.2 local	variant
CNV duplication 6q14.1 local	variant
CNVPartition local	drug
CNVs	variant
cocaine	phenotype
COGEND	cohort
Collaborative Study on the Genetics of Alcoholism (COGA)	cohort
conduct disorder	phenotype
controls	cohort
copy number variants	variant
copy number variation	variant
Copy number variations (CNVs) local	variant
Database of Genomic Variants local	cohort
Deletion at 7q11.23 local	variant
DSM-IV alcohol dependence	phenotype
Duplication at 17p11.2 local	variant
earlier age of heavy and regular alcohol use local	phenotype
Early-onset male alcoholics local	cohort
epilepsy	phenotype
European population	cohort
excessive alcohol consumption	phenotype
families	cohort
FSCD	cohort
FTND score local	drug
genetic variants	cohort
Geneva	cohort
genome wide association study local	cohort
GTF2H2 local	gene
GTF2H2D local	gene
human behavior	phenotype
Illumina Human1M array	drug
intellectual disabilities local	phenotype
language delay	phenotype
major depressive disorder	phenotype
marijuana	phenotype
marijuana dependence	phenotype
mental retardation	phenotype
microcephaly	phenotype
minor dysmorphisms local	phenotype
more alcohol symptoms local	phenotype
NAIP local	gene
neurological disorders	phenotype
nicotine	drug
nicotine dependence	phenotype
Non-dependent alcohol exposed controls local	cohort
OCLN local	gene
PennCNV	gene
peripheral nervous system	anatomy
pseudo-TORCH syndrome local	phenotype
qPCR	drug
QuantiSNP	drug
Region X local	variant
RNAse P local	gene
SAGE	cohort
schizophrenia	phenotype
SERF1 local	gene
SERF1B local	gene
simplex families	cohort
single nucleotide polymorphism	variant
SMA3 local	gene
SMA4 local	gene
SMN2 local	gene
SNP	cohort
spasticity	phenotype
spinal muscular atrophy	phenotype
TaqMan CNV probe local	drug
Williams-Beuren Syndrome local	phenotype

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