The CRHR1 gene, trauma exposure, and alcoholism risk: a test of G × E effects.

paper Cited Public

Authors: Ray, L A; Sehl, M; Bujarski, S; Hutchison, K; Blaine, S; Enoch, M-A
Year: 2013
Journal: Genes, brain, and behavior
PMID: 23473364
DOI: 10.1111/gbb.12032
PMCID: PMC4139150

Figure 1

CRHR1 haplotype block structure in CaucasiansThe figure was generated using Haploview software (Barrett et al. 2005). Haplotype block 1 extends from SNP rs4792886 to rs242924 (8 kb). Haplotype block 2 extends from SNP rs242942 to rs1876829 (19 kb). The numbers in the squares (0 – 100) refer to pairwise linkage disequilibrium (LD) measured as D’. Haplotype blocks were defined using a setting of average pairwise D’ of ≥ 80. The darker the square, the greater the LD.

LLM interpretation

This is a linkage disequilibrium (LD) plot generated by Haploview showing the haplotype block structure of the CRHR1 gene in Caucasians. The visualization uses a color-coded heatmap where darker red squares indicate higher pairwise LD (measured as D'), with numerical values from 0 to 100 provided in the squares. Two distinct haplotype blocks are outlined in black: Block 1 (8 kb) spanning from SNP rs4792886 to rs242924, and Block 2 (19 kb) spanning from SNP rs242942 to rs1876829.

Figure 2

Percentage of individuals with a given block1 haplotype and trauma exposure status who meet criteria for alcohol dependencePercentages were calculated from raw counts for each haplotype, trauma status, and alcohol dependence category. For example, of those individuals with the H1/H1 diplotype who were exposed to trauma, 63% were found to be alcohol dependent. A smaller percentage (34%) of those individuals who carried the H1/H1 diplotype and were not exposed to trauma were alcohol dependent.

LLM interpretation

This grouped bar chart shows the relative frequency of alcohol dependence across three CRHR1 Haplotype Block 1 diplotypes (H2/H2, H1/H2, H1/H1), stratified by trauma exposure. In the "trauma" group, the percentage of alcohol-dependent individuals is higher than the control group for all diplotypes. Conversely, in the "no trauma" group, the control group shows a higher relative frequency than the alcohol-dependent group across all diplotypes.

Figure 3

Percentage of individuals with a given block 2 haplotype and trauma exposure status who suffer from alcohol dependencePercentages were calculated from raw counts for each haplotype, trauma status, and alcohol dependence category. We observe that 56% of individuals who carried the H1/H1 diplotype and were exposed to trauma were found to be alcohol dependent. This percentage is slightly smaller than the percentage (62%) of individuals who carried the H4/H4 reference diplotype and were exposed to trauma who were found to be alcohol dependent. In the absence of trauma, 33% of individuals carrying the H1/H1 diplotype were found to be alcohol dependent.

LLM interpretation

This grouped bar chart shows the relative frequency of alcohol dependence versus control groups across three CRHR1 haplotype block 2 diplotypes (H4/H4, H1/H4, H1/H1), categorized by trauma exposure status. In the "trauma" group, the relative frequency of alcohol dependence is higher than the control for all diplotypes, whereas in the "no trauma" group, the control frequency is consistently higher than that of alcohol dependence. The y-axis represents relative frequency from 0% to 80%, and no statistical significance markers are present on the chart.

#	Section	Preview
0	INTRODUCTION	Twin and adoption studies have shown that the heritability of alcoholism may be as high as 50-60%…
1	INTRODUCTION	childhood trauma, which permanently alters the stress response to acute stressors into adulthood…
2	INTRODUCTION	In light of the literature supporting the biological and clinical plausibility of CRHR1 involvement…
3	INTRODUCTION	the gene. Bradley et al (2008) identified a three single nucleotide polymorphism (SNP) haplotype…
4	INTRODUCTION	follow-up study of the adolescent sample reported an interaction between these two markers and…
5	INTRODUCTION	In light of the literature reviewed above, the aim of our study was to determine the main and…
6	MATERIALS AND METHODS — Participants	Data were culled from the Study of Addiction: Genetics and Environment (SAGE) genome-wide…
7	MATERIALS AND METHODS — Psychiatric Assessments	A common psychiatric assessment was performed across all three studies based on the Semi-Structured…
8	MATERIALS AND METHODS — Traumatic Stress Exposure in Adulthood	Exposure to traumatic stress was derived from the PTSD items of the SSAGA, the Semi Structured…
9	MATERIALS AND METHODS — Traumatic Stress Exposure in Adulthood	or killed; a flood, earthquake, large fire, or other disaster; an airplane crash or serious car…
10	MATERIALS AND METHODS — Genotypes	All DNA samples were genotyped on the Illumina Human 1M beadchip. After extensive data cleaning and…
11	MATERIALS AND METHODS — Statistical Analyses	Since there is no known functional CRHR1 polymorphism we used a haplotype-driven approach to capture…
12	MATERIALS AND METHODS — Haplotype Analyses	Haplotype frequencies were estimated using a Bayesian approach implemented with PHASE (Stephens &…
13	MATERIALS AND METHODS — Secondary SNP Analyses	In order to determine which SNPs might be contributing to a haplotype effect, a series of logistic…
14	RESULTS — Haplotype Analyses	Haplotype blocks and pairwise D’ values are shown in Figure 1. Two haplotype blocks were…
15	RESULTS — Haplotype block 1: Haplotype Analyses	From Table 3a it can be seen that there were two major haplotypes of nearly equal frequency (denoted…
16	RESULTS — Haplotype block 1: Haplotype Analyses	In addition, the H1 haplotype was associated with greater alcoholism risk (p = 0.032). The H1 ×…
17	RESULTS — Haplotype Block 1: Secondary SNP Analyses	As shown in Table 2, a significant (corrected p < .025) genotype × traumatic stress interaction on…
18	RESULTS — Haplotype Block 2: Haplotype Analyses	A similar pattern of results emerged for haplotype block 2 (see Table 6). There was a simple effect…
19	RESULTS — Haplotype Block 2: Secondary SNP Analyses	As shown in Table 2, a significant (corrected p < .025) genotype × traumatic stress interaction on…

Name	Type
900 kb inversion polymorphism local	variant
ACTH	drug
addiction	phenotype
adolescents	cohort
adolescent sample	cohort
adult drinkers local	cohort
Adulthood traumatic stress exposure local	phenotype
Adults without trauma local	cohort
adult trauma exposure local	phenotype
African American	cohort
African heritage local	cohort
alcohol	phenotype
alcohol abuse	phenotype
alcohol dependence	phenotype
Alcoholic cases local	cohort
alcoholism	phenotype
alcoholism risk	phenotype
Alcoholism susceptibility local	phenotype
alcohol self-administration	phenotype
Alcohol Use	phenotype
Alcohol Use Disorder	phenotype
alcohol use disorders	phenotype
anxiety	phenotype
block 1	variant
Block 1 haplotype local	variant
block 2 local	variant
Brain-specific knockout mice local	cohort
cases	cohort
Caucasian cohort	cohort
Caucasians	cohort
Caucasian sample	cohort
childhood trauma	phenotype
Childhood trauma cohort local	cohort
chronic alcoholism	phenotype
chronic stress exposure local	phenotype
Chronic stress exposure local	phenotype
cocaine	phenotype
COGEND	cohort
Collaborative Study on the Genetics of Alcoholism (COGA)	cohort
control animals	cohort
controls	cohort
cortisol	drug
CRF	drug
CRF system dysregulation local	phenotype
CRH	gene
CRHBP	gene
CRHR1	gene
CRHR1 antagonist local	drug
CRHR1 haplotype local	variant
CRHR1 haplotypes local	variant
CRHR1 SNP local	variant
CRHR1 SNPs local	variant
depression	phenotype
dexamethasone	drug
disease	phenotype
drug dependence	phenotype
drugs	drug
Elevated cortisol response local	phenotype
escalation of alcohol intake local	phenotype
European population	cohort
extended amygdala	anatomy
extra hypothalamic CRF system local	anatomy
Extra hypothalamic CRF system local	drug
Fkbp5	gene
FSCD	cohort
H1 local	variant
H1/H1 local	variant
H1/H1 diplotype local	variant
H1 haplotype local	variant
H1 haplotype block 2 local	variant
H2 local	variant
H2/H2 diplotype local	variant
H2 haplotype local	variant
H3 local	variant
H4 local	variant
H4/H4 local	variant
H7 local	variant
haplotype block 1 local	variant
haplotype H1 local	variant
heavy drinking	phenotype
HPA axis	anatomy
hypothalamus	anatomy
Illumina Human1M array	drug
lifetime risk of alcoholism local	phenotype
major depressive disorder	phenotype
MGC57346 local	gene
mood disorders	phenotype
neglect	phenotype
nicotine	drug
Non-dependent controls local	cohort
non-physical or sexual trauma local	phenotype
Non-physical or sexual trauma local	phenotype
No trauma group local	cohort
physical abuse	phenotype
physical trauma	phenotype
posttraumatic stress disorder	phenotype
Post-Traumatic Stress Disorder	phenotype
Primary schizophrenia patients local	cohort
psychiatric functioning local	phenotype
rape	phenotype
recent stress exposure local	phenotype
Recent stress exposure local	phenotype
Relapse-like drinking	phenotype
rs110402 local	variant
rs16940655 local	variant
rs16940686 local	variant
rs173365 local	variant
rs17689966 local	variant
rs1876829 local	variant
rs1876831 local	variant
rs242924 local	variant
rs242938 local	variant
rs242942 local	variant
rs3811939 local	variant
rs4792882 local	variant
rs4792886 local	variant
rs7209436 local	variant
SAGE	cohort
SAGE dataset	cohort
schizophrenia	phenotype
sex	phenotype
sexual trauma	phenotype
SSACD local	cohort
SSAGA	cohort
SSAND local	cohort
stressful life events	phenotype
stress-induced augmentation of alcohol intake local	phenotype
Stress-induced craving	phenotype
stress-induced reinstatement	phenotype
stress response	phenotype
TAT haplotype local	variant
trauma	phenotype
Trauma exposed individuals local	cohort
trauma exposure	phenotype
traumatic experiences	phenotype
traumatic stress	phenotype
Worse psychiatric functioning local	phenotype

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