The Role of Trauma in Alcoholism Risk and Age of Alcoholism Onset

By Colleen M. Farrelly
University of Miami, Miller School of Medicine (Biostatistics Division)
cfarrelly@med.miami.edu
Spring 2013, Statistical Computing Course Project

Abstract:
Trauma is an important predictor of alcoholism risk, as well as age of onset; those experiencing more
types of trauma tend to be at increased risk. In addition, paternal and maternal history of alcoholism is
highly related to alcoholism risk, and paternal history remains significant after controlling for trauma.
Limitations of these findings include univariate testing, and follow-ups with more sophisticated age-to-
onset models, such as random survival forests and boosted survival models, should be done to understand
the interactions of trauma and other genetic and social risk factors to better understand the etiology of
alcoholism.

Introduction
Alcoholism presents a major public health burden in the United States, affecting an estimated
7.0% of the adult population (CDC,2012), and only about 15-33% of those in need of treatment for
alcoholism actually receive it (Cunningham & Breslin, 2004). Understanding the genetic and
environmental risks for alcoholism, as well as identifying subpopulations of alcohol-dependent persons,
has shown promise in developing efficacious prevention and treatment programs (Begleitter et al., 1995;
Sinha et al., 2011). Genetic risk factors have historically been thought to influence alcoholism risk, and
many landmark and recent studies have documented general genetic risk (Cloninger et al., 1981;
Cloninger et al., 1988; Johnson et al., 2010). Of particular interest recently is the classification and
clinical trajectories of alcoholism subtypes with respect to age of onset (Johnson et al., 2010), as this has
been previously linked to disease severity and treatment response (Irwin et al., 1990). In addition, it is
thought that family history of alcoholism plays a large role in early-onset alcoholism (Cloninger et al.,
1981; Cloninger et al., 1988; Johnson et al., 2010).
In addition to age of onset, many previous studies have considered the role of trauma as a risk
factor for alcoholism and have shown that trauma and alcohol abuse/dependence are, indeed, intricately
connected (Keane and Wolf, 1990; McFarlane, 1998; Stewart et al., 1998; Shipherd et al., 2005; Jacobson
et al., 2008; Coffey et al., 2007; Flood et al., 2009), whether trauma occurred in childhood, adulthood, or
both (Maguen et al., 2008; Cornelius et al., 2010, Perkonnig et al., 2000). Previous trauma and post-
traumatic stress disorder symptoms have been repeatedly shown to increase relapse risk in patients
undergoing drug or alcohol treatment (Read et al., 2004; Norman et al., 2007; Norman et al., 2010;
Shipherd et al., 2005). Most notably affected by this link between trauma and alcohol abuse/dependence
are combat veterans, who are at increased risk of future trauma (Orcutt et al., 2002), health problems in
general and related to alcohol abuse/dependence (Schnurr et al., 2000), and comorbid post-traumatic
stress disorder and alcoholism (Dedert et al., 2009; Keane and Wolf, 1990). In addition, prevalence of
civilian trauma exposure has been estimated at 25%-50% for adolescents and 50%-75% for non-
institutionalized adults (Perkonnig et al., 2000; Kessler et al., 1995; Anders et al., 2012; Goodman et al.,
1998). Because rates of trauma are high in communities and more active-duty soldiers are returning
home, it is important to understand the interrelationship of trauma and alcohol abuse to better prevent
onset of alcohol abuse following trauma and to treat patients suffering from both substance abuse and
post-traumatic stress disorder.
This study hopes to shed light on the role of trauma in both the risk of developing alcoholism and,
for childhood traumas, predicting the age of onset of alcoholism in a Caucasian subset of participants
within larger a genome-wide association case-control study collected by the Collaborative Studies on
Genetics of Alcoholism Study (COGA), which provides demographic, trauma history, and family history
of alcoholism data in addition to genomic data. It is hypothesized that a history of trauma will show
higher odds of lifetime prevalence of alcohol dependence and that participants reporting childhood trauma
will show earlier age of onset than participants who did not experience childhood trauma, even after
controlling for demographic and familial risk factors.

Methods
Participants
Participants included 167 Caucasian adults obtained from the COGA dataset (Begleiter et al.,
1995), including 85 cases and 82 controls. Cases were defined as those meeting DSM-IV criteria for
alcohol dependence during their lifetime. In this sample, 11 reported maternal alcoholism while 19
reported paternal alcoholism. Mean education of participants was one year of college (sd=2.3 years), and
median income was $20,000-$29,999 annually. Ages ranged from 18 to 70 years, with a mean of 43.3
years (sd=10.5 years), and males accounted for 84 participants (50%). The majority of participants grew
up in a small city or rural area.

Measurements
Non-genomic factors measured through a survey and used for these analyses included 5
types of binary response childhood and adulthood traumas, gender, case status, age of alcoholism onset
defined as age at which participant first met DSM-IV criteria for alcohol dependence (continuous),
educational attainment measured by highest grade completed (continuous), income range (interval), and
maternal and paternal alcohol dependence history according to the above definition of alcohol
dependence (binary). Because participants reporting trauma were overwhelmingly Caucasian, only
Caucasian participants were selected for analysis.
Trauma experiences include childhood physical abuse (defined as physical punishment hard
enough to hurt the next day or severe enough to warrant medical attention), childhood sexual abuse
(defined as any sexual contact with someone 5 years older than the participant before the age of 16),
adulthood non-assault trauma (defined as witnessing a natural disaster, such as a flood, hurricane, or
earthquake), adulthood physical trauma (defined as military combat/war situations, being the victim of a
violent crime, or experiencing a life-threatening accident or illness), and adulthood sexual trauma
(defined as unwanted sexual contact, whether completed or attempted).

Analyses
This study first investigated the association of five distinct traumatic experiences, as well as
number of trauma types experienced, with alcohol dependence through the use of a series of logistic
regression models adjusted for demographic factors (which may serve as confounders) and possible
genetic link by family history of alcohol dependence, accompanied by a Bonferroni correction for
multiple tests (Holm, 1979). This was computed via the SAS proc logistic statement in SAS 9.3 (SAS
Institute Inc., 2011).
The second aim of this study was to examine the role of childhood trauma in age of onset of
alcohol dependence. (Adulthood trauma was not considered, as age-of-onset was during adolescents and
young adulthood for many cases and there was no way to assess whether adulthood trauma preceded the
onset of alcohol dependence.) Therefore, to test this aim, Kaplan-Meier survival curves were run for both
childhood trauma types to assess whether the proportional hazards assumption was met (Kleinbaum &
Klein, 2012). If this assumption held for either trauma, univariate and multivariate Cox regression models
(Tang et al., 1996) were run for that trauma meeting the proportional hazards assumption (multivariate
controlling for demographic variables and family history of alcoholism). This was also run in SAS 9.3,
using the proc lifetest and proc phreg procedures (SAS Institute Inc., 2011).

Results
Hypothesis 1
The majority of participants reported experiencing at least one of the traumas within their lifetime
(52.1%), with 25.7% reporting 2 or more trauma types and 13.2% reporting 3 or more trauma types. The
most commonly experienced trauma type was adulthood non-assault trauma, including natural disasters,
and the least commonly experienced trauma type was adulthood sexual assault (Table 1).
Three of the five trauma exposures—childhood physical abuse, childhood sexual abuse, and adult
assault trauma—were associated with a statistically significant higher risk of alcoholism (Table 1), even
when adjusting for demographic and family history variables. Of particular note are the high odds ratios
for significant predictors of lifetime case status. Total trauma history proved to be a very strong predictor
of alcoholism status, with an extremely high odds ratio noted for no trauma history vs. 3 or more lifetime
trauma types and more moderate odds ratios for no trauma history vs. 1 and vs. 2 lifetime trauma types.
Differences did not exist among groups with higher numbers of trauma compared to each other, which
may owe to small group size, as the majority of participants reported no trauma history. However,
confounding may be present, as income and education showed relationships in each of the logistic
regressions.
Table 1: Logistic Regression Results
Regression Number (%) Wald X2 Odds Ratio 95% CI of OR p-value Significant
Trauma Reporting (OR) Predictors
Trauma
Childhood 33 (19.8%) 7.84 6.68 1.77-25.27 0.005** Education*,
Physical Income***
Abuse
Childhood 38 (22.8%) 11.86 8.83 2.56-30.47 <0.001*** Education*,
Sexual Abuse income***,
Gender*
Adulthood 50 (30.0%) 3.14 2.45 0.91-6.61 0.076 Income***,
Non-Assault Education*
Adulthood 22 (13.2%) 7.93 12.03 2.13-67.93 0.005** Income***
Physical
Adulthood 15 (9.0%) 2.99 4.67 0.81-26.84 0.084 Education*,
Sexual Income***
Total Trauma 87 (52.1%) 16.58 Significant Significant for <0.001*** Education*,
reporting 1+ for 0 vs. 1+ 0 vs. 1+ Income***
traumas traumas
* p<0.05, ** p<0.01, *** p<0.001 under Bonferroni correction. Significant predictors include any other significant factors
identified in the logistic regression model.

Hypothesis 2
Kaplan-Meier curves showed that cases had a median onset of 23 years (95% CI=22-26 years)
with the vast majority of cases having an onset of alcoholism before age 30 (Table 2, Table 3). Both
childhood traumas met the proportional hazards assumption (Figure 1 and 2) and were associated with
earlier onset of alcoholism (Table 4).

Figure 1: Survival Curve for Childhood Physical Abuse

Figure 2: Kaplan-Meier Survival Curve for Childhood Sexual Abuse

Table 2: Age of Onset Quartiles for Cases

Case Onset Quantiles
Percen Point 95% Confidence Interval
t Estimate [Lower Upper)
75% 30 28 33
50% 23 22 26
25% 20 19 21
Table 3: Summary of Kaplan-Meier Analysis of Cases
Product-Limit Survival Estimates of Cases
Age of Numbe Observe Surviva Failur Survival Numbe Numbe
Alcoholis r d l e Standar r r
m Onset at Risk Events d Failed Left
Error
10 85 0 1.00 0 0 0 85
20 67 4 0.74 0.26 0.05 22 63
30 25 5 0.24 0.76 0.05 65 20
40 5 2 0.04 0.96 0.02 82 3
50 1 1 0 1.00 . 85 0

Adding in demographic factors and family history significantly changed the hazard ratios for both
traumas, and many factors significantly contributed to predicting age of onset. Of particular note is the
large hazard ratio obtained for paternal history of alcoholism in the physical abuse model (HR=1.98),
suggesting that genetics may play a role in determining the age of onset in addition to trauma (Table 4).
Because paternal history was a predictor in the physical risk model and because results didn’t agree with
previous studies, subsequent analyses to test if family history alone predicted age of onset were run
(Table 5) and a future study using this dataset plans to investigate the seemingly complex relationship of
genetic risk factors, trauma, and demographic factors in predicting age of onset of alcohol dependence
through boosted tree survival models and random survival forest models.

Table 4: Summary of Cox Proportional Hazards Analyses

Log-rank X2 p-value Univariate Multivariate Other Significant
Hazard Ratio Hazard Ratio Predictors
(95% CI) (95% CI)
Physical Abuse 35.67 <0.001 3.87 (2.41-6.24) 2.14 (1.27-3.61) Age, Education,
Gender, Paternal
History
Sexual Abuse 31.05 <0.001 3.51 (2.20-5.61) 2.71 (1.62-4.55) Age, Education,
Gender, Income

Table 5: Summary of Genetic Risk and Age of Onset

Log-rank X2 p-value Univariate
Hazard Ratio
(95% CI)
Maternal 17.36 <0.001 3.80 (1.94-7.43)
History
Paternal 22.88 <0.001 3.62 (2.06-6.33)
History

Discussion
 This study found that a history of trauma inflicted by another person substantially increased a
person’s likelihood of reporting lifetime alcoholism, which agrees with previous research (Coffey et al.,
2007; Flood et al., 2009; Cornelius et al., 2010). There was also evidence of elevated risk for those
reporting multiple trauma types compared to those without a history of trauma, though no dose response
was found. Given the low rates of multiple traumas, it is possible that the sample size was too small to
detect meaningful differences among these smaller groups.
Regrettably, the data did not provide number of traumatic events experienced, which may have
helped to shed light on this relationship and test for a dose-response for each of the given traumas. This
would likely be of use in understanding the risk of alcoholism at various combat frequency/duration
levels or in relation to duration and severity of childhood abuse. However, these findings, especially the
extremely high odds ratios found between those who never experienced trauma and those who
experienced 2+ or 3+ different types of trauma, and the results of the survival analyses suggest that those
who experienced childhood abuse and subsequently experience trauma as an adult may be at particularly
high risk for developing alcoholism and that intervening before multiple trauma types accumulate may be
of use in preventing alcoholism (Norman et al., 2010).
In addition, childhood trauma significantly decreased the age of onset of alcoholism, such that
those reporting childhood trauma showed an earlier onset of alcoholism than those without such a history.
This suggests that preventing trauma, particularly trauma occurring in childhood, and intervening after a
traumatic event may be of use in the prevention of alcoholism and that trauma history should be
considered in alcoholism treatment, particularly for young people. Very few studies have examined
factors influencing the age of alcoholism onset, and most of those concentrate on age of drinking
initiation as the risk factor of interest (Grant & Dawson, 1997; Hingson et al., 2006; Ehlers et al., 2010).
To the author’s knowledge, this is the first study examining trauma and alcoholism onset using a survival
analysis framework.
Also of note was the role of family history of alcoholism in predicting the age to onset of
participant alcoholism, which seems to involve a pathway through demographic factors. Previous
typology studies of alcoholism, identifying early- and late-onset types, have posited that early-onset
alcoholism has a strong family history component, especially with respect to paternal alcoholism
(Johnson et al., 2010; Cloninger et al., 1981), and many genome-wide association studies have found
specific single nucleotide polymorphisms associated with an increased risk of alcoholism in general
(Edenburg et al., 2010; Treutlein et al., 2009; Treutlein & Rietschel, 2011). Future studies may wish to
assess age to onset of alcoholism by these genetic factors to determine if any particular genes are
associated with timing of alcoholism onset, as well as test a mediation survival model to examine whether
or not genetic risk acts through future education and income to predict onset of alcoholism.
 In all, this study has provided a foundation for future studies of trauma and alcoholism risk and
age of onset, as well as documented evidence that genetics may play a role in determining the timing of
alcoholism onset. Given the limited generalizability of this racially homogenous sample, future studies
may wish to replicate this in diverse populations, as well as investigate the role of income and education
as potential confounders or partial mediators. Future studies may also wish to examine severity and
frequency of trauma, as well as better distinguish between trauma types. In addition, given the link
between family history of alcoholism and a person’s age to onset survival, future studies should also
examine specific genetic factors in conjunction with trauma and important environmental factors, such as
income and education, to better understand who is at risk for early development of alcoholism.
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