Genes, the Environment, and Depressive Symptom Scores in the Multi-Ethnic Study of Atherosclerosis.

Genetic factors, stressors operating over the life course, and various aspects of social context have been shown to play a role in the etiology of depressive symptoms. However, empirical studies that investigate environmental and genetic factors, as well as their interactions, remain rare. First, traditional genetic analysis methods were employed to investigate the genetic determinants of depressive symptoms at the single-nucleotide polymorphism (SNP) level, incorporating different approaches to analyzing longitudinal outcomes (baseline measure, measures averaged over exam visits, and a repeated measures); secondly, state-of-the-art genomic region-level analysis methods were utilized to identify genomic regions associated with depressive symptoms; and finally, genomic region by environment (G x E) analysis methods were used to examine of the extent to which individual- and neighborhood-level social exposures modify the genetic effects of depressive symptoms. All analyses were performed both within and across multiple ethnicities (African, European, Hispanic, and Chinese Americans). This work includes evidence that incorporating longitudinal measures (through the averaged or repeated measures approach) results in smaller p-values and an increase in the number of single-nucleotide polymorphisms (SNP) reaching genome-wide suggestive level, as well as both genomic-region determinants of depressive symptom scores and modification of those regions by social environments at both an individual- and neighborhood-level (chronic burden, social support, or neighborhood index score). This dissertation represents an important contribution to life sciences in several ways: first, this is the first analysis that incorporates novel methods with depressive symptom outcomes; second, through the investigation of the association of genetic variants and depressive symptoms across multiple ethnicities; third, through a detailed comparison of how longitudinal data can be used to define a mental health phenotypes in the context of genetic studies; and finally through the use of both individual- and neighborhood-level interactions with genetic information at both an individual SNP level and a region level. Replicating these initial findings in other studies will help motivate efforts to reduce depressive symptom burden through modifiable environmental factors in individuals with certain genetic profiles.PHDEpidemiological ScienceUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/107163/1/ebakshis_1.pd

Revisiting Rose: Comparing the benefits and costs of population-wide and targeted interventions.

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/61295/1/ahern et al_revisiting rose_2008.pd

A genome-wide association study of depressive symptoms.

BACKGROUND: Depression is a heritable trait that exists on a continuum of varying severity and duration. Yet, the search for genetic variants associated with depression has had few successes. We exploit the entire continuum of depression to find common variants for depressive symptoms. METHODS: In this genome-wide association study, we combined the results of 17 population-based studies assessing depressive symptoms with the Center for Epidemiological Studies Depression Scale. Replication of the independent top hits (p<1×10(-5)) was performed in five studies assessing depressive symptoms with other instruments. In addition, we performed a combined meta-analysis of all 22 discovery and replication studies. RESULTS: The discovery sample comprised 34,549 individuals (mean age of 66.5) and no loci reached genome-wide significance (lowest p = 1.05×10(-7)). Seven independent single nucleotide polymorphisms were considered for replication. In the replication set (n = 16,709), we found suggestive association of one single nucleotide polymorphism with depressive symptoms (rs161645, 5q21, p = 9.19×10(-3)). This 5q21 region reached genome-wide significance (p = 4.78×10(-8)) in the overall meta-analysis combining discovery and replication studies (n = 51,258). CONCLUSIONS: The results suggest that only a large sample comprising more than 50,000 subjects may be sufficiently powered to detect genes for depressive symptoms

A Genome-Wide Association Study of Depressive Symptoms

<p>Background: Depression is a heritable trait that exists on a continuum of varying severity and duration. Yet, the search for genetic variants associated with depression has had few successes. We exploit the entire continuum of depression to find common variants for depressive symptoms.</p><p>Methods: In this genome-wide association study, we combined the results of 17 population-based studies assessing depressive symptoms with the Center for Epidemiological Studies Depression Scale. Replication of the independent top hits (p <1 x 10(-5)) was performed in five studies assessing depressive symptoms with other instruments. In addition, we performed a combined meta-analysis of all 22 discovery and replication studies.</p><p>Results: The discovery sample comprised 34,549 individuals (mean age of 66.5) and no loci reached genome-wide significance (lowest p = 1.05 x 10(-7)). Seven independent single nucleotide polymorphisms were considered for replication. In the replication set (n = 16,709), we found suggestive association of one single nucleotide polymorphism with depressive symptoms (rs161645, 5q21, p = 9.19 x 10(-3)). This 5q21 region reached genome-wide significance (p = 4.78 x 10(-8)) in the overall meta-analysis combining discovery and replication studies (n = 51,258).</p><p>Conclusions: The results suggest that only a large sample comprising more than 50,000 subjects may be sufficiently powered to detect genes for depressive symptoms.</p>

A genome-wide association study of depressive symptoms.

BackgroundDepression is a heritable trait that exists on a continuum of varying severity and duration. Yet, the search for genetic variants associated with depression has had few successes. We exploit the entire continuum of depression to find common variants for depressive symptoms.MethodsIn this genome-wide association study, we combined the results of 17 population-based studies assessing depressive symptoms with the Center for Epidemiological Studies Depression Scale. Replication of the independent top hits (p&lt;1×10(-5)) was performed in five studies assessing depressive symptoms with other instruments. In addition, we performed a combined meta-analysis of all 22 discovery and replication studies.ResultsThe discovery sample comprised 34,549 individuals (mean age of 66.5) and no loci reached genome-wide significance (lowest p = 1.05×10(-7)). Seven independent single nucleotide polymorphisms were considered for replication. In the replication set (n = 16,709), we found suggestive association of one single nucleotide polymorphism with depressive symptoms (rs161645, 5q21, p = 9.19×10(-3)). This 5q21 region reached genome-wide significance (p = 4.78×10(-8)) in the overall meta-analysis combining discovery and replication studies (n = 51,258).ConclusionsThe results suggest that only a large sample comprising more than 50,000 subjects may be sufficiently powered to detect genes for depressive symptoms

A genome-wide association study of depressive symptoms

Background: Depression is a heritable trait that exists on a continuum of varying severity and duration. Yet, the search for genetic variants associated with depression has had few successes. We exploit the entire continuum of depression to find common variants for depressive symptoms. Methods: In this genome-wide association study, we combined the results of 17 population-based studies assessing depressive symptoms with the Center for Epidemiological Studies Depression Scale. Replication of the independent top hits (p<1×10-5) was performed in five studies assessing depressive symptoms with other instruments. In addition, we performed a combined meta-analysis of all 22 discovery and replication studies. Results: The discovery sample comprised 34,549 individuals (mean age of 66.5) and no loci reached genome-wide significance (lowest p = 1.05×10-7). Seven independent single nucleotide polymorphisms were considered for replication. In the replication set (n = 16,709), we found suggestive association of one single nucleotide polymorphism with depressive symptoms (rs161645, 5q21, p = 9.19×10-3). This 5q21 region reached genome-wide significance (p = 4.78×10-8) in the overall meta-analysis combining discovery and replication studies (n = 51,258). Conclusions: The results suggest that only a large sample comprising more than 50,000 subjects may be sufficiently powered to detect genes for depressive symptoms