title: GENOME-WIDE ASSOCIATION STUDY (GWAS) AND GENOME-WIDE BY ENVIRONMENT INTERACTION STUDY (GWEIS) OF DEPRESSIVE SYMPTOMS IN AFRICAN AMERICAN AND HISPANIC/LATINA WOMEN.
abstract: BACKGROUND
  Genome-wide association studies (GWAS) have made little progress in identifying variants linked to depression. We hypothesized that examining depressive symptoms and considering gene-environment interaction (GxE) might improve efficiency for gene discovery. We therefore conducted a GWAS and genome-wide by environment interaction study (GWEIS) of depressive symptoms.
  
  
  METHODS
  Using data from the SHARe cohort of the Women's Health Initiative, comprising African Americans (n = 7,179) and Hispanics/Latinas (n = 3,138), we examined genetic main effects and GxE with stressful life events and social support. We also conducted a heritability analysis using genome-wide complex trait analysis (GCTA). Replication was attempted in four independent cohorts.
  
  
  RESULTS
  No SNPs achieved genome-wide significance for main effects in either discovery sample. The top signals in African Americans were rs73531535 (located 20 kb from GPR139, P = 5.75 × 10(-8) ) and rs75407252 (intronic to CACNA2D3, P = 6.99 × 10(-7) ). In Hispanics/Latinas, the top signals were rs2532087 (located 27 kb from CD38, P = 2.44 × 10(-7) ) and rs4542757 (intronic to DCC, P = 7.31 × 10(-7) ). In the GEWIS with stressful life events, one interaction signal was genome-wide significant in African Americans (rs4652467; P = 4.10 × 10(-10) ; located 14 kb from CEP350). This interaction was not observed in a smaller replication cohort. Although heritability estimates for depressive symptoms and stressful life events were each less than 10%, they were strongly genetically correlated (rG = 0.95), suggesting that common variation underlying self-reported depressive symptoms and stressful life event exposure, though modest on their own, were highly overlapping in this sample.
  
  
  CONCLUSIONS
  Our results underscore the need for larger samples, more GEWIS, and greater investigation into genetic and environmental determinants of depressive symptoms in minorities.
authors.affiliation: Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts.|Department of Psychiatry, Harvard Medical School, Boston, Massachusetts.|Stanley Center for Psychiatric Research, The Broad Institute of Harvard and MIT, Cambridge, Massachusetts.
authors.forename: Erin C
authors.initials: EC
authors.lastname: Dunn
authors.affiliation: Center for Experimental Drugs and Diagnostics, Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Anna
authors.initials: A
authors.lastname: Wiste
authors.affiliation: Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts.|Division of Neurocritical Care, Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts.|Program in Medical and Population Genetics, The Broad Institute of Harvard and MIT, Cambridge, Massachusetts.
authors.forename: Farid
authors.initials: F
authors.lastname: Radmanesh
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia.
authors.forename: Lynn M
authors.initials: LM
authors.lastname: Almli
authors.affiliation: Department of Biostatistics, University of Washington, Seattle, Washington.
authors.forename: Stephanie M
authors.initials: SM
authors.lastname: Gogarten
authors.affiliation: Department of Biostatistics, University of Washington, Seattle, Washington.
authors.forename: Tamar
authors.initials: T
authors.lastname: Sofer
authors.affiliation: Institute for Social Research, University of Michigan, Ann Arbor, Michigan.
authors.forename: Jessica D
authors.initials: JD
authors.lastname: Faul
authors.affiliation: Department of Epidemiology, University of Michigan, Ann Arbor, Michigan.
authors.forename: Sharon L R
authors.initials: SL
authors.lastname: Kardia
authors.affiliation: Department of Epidemiology, University of Michigan, Ann Arbor, Michigan.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Smith
authors.affiliation: Institute for Social Research, University of Michigan, Ann Arbor, Michigan.
authors.forename: David R
authors.initials: DR
authors.lastname: Weir
authors.affiliation: Department of Epidemiology, University of Michigan, Ann Arbor, Michigan.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhao
authors.affiliation: Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts.|Department of Psychiatry, Harvard Medical School, Boston, Massachusetts.|Stanley Center for Psychiatric Research, The Broad Institute of Harvard and MIT, Cambridge, Massachusetts.
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Soare
authors.affiliation: Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands.
authors.forename: Saira S
authors.initials: SS
authors.lastname: Mirza
authors.affiliation: Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands.|Department of Psychiatry, Erasmus Medical Center, Rotterdam, the Netherlands.
authors.forename: Karin
authors.initials: K
authors.lastname: Hek
authors.affiliation: Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands.|Department of Psychiatry, Erasmus Medical Center, Rotterdam, the Netherlands.
authors.forename: Henning
authors.initials: H
authors.lastname: Tiemeier
authors.affiliation: Department of Psychiatry and Behavioral Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin.
authors.forename: Joseph S
authors.initials: JS
authors.lastname: Goveas
authors.affiliation: Center for Women's Health and Health Disparities Research, Department of Obstetrics and Gynecology, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin.
authors.forename: Gloria E
authors.initials: GE
authors.lastname: Sarto
authors.affiliation: Department of Biostatistical Sciences, Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina.
authors.forename: Beverly M
authors.initials: BM
authors.lastname: Snively
authors.affiliation: Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
authors.forename: Marilyn
authors.initials: M
authors.lastname: Cornelis
authors.affiliation: Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York.
authors.forename: Karestan C
authors.initials: KC
authors.lastname: Koenen
authors.affiliation: Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
authors.forename: Peter
authors.initials: P
authors.lastname: Kraft
authors.affiliation: Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Shaun
authors.initials: S
authors.lastname: Purcell
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia.
authors.forename: Kerry J
authors.initials: KJ
authors.lastname: Ressler
authors.affiliation: Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts.|Division of Neurocritical Care, Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts.|Program in Medical and Population Genetics, The Broad Institute of Harvard and MIT, Cambridge, Massachusetts.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Rosand
authors.affiliation: Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York.
authors.forename: Sylvia
authors.initials: S
authors.lastname: Wassertheil-Smoller
authors.affiliation: Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts.|Department of Psychiatry, Harvard Medical School, Boston, Massachusetts.|Stanley Center for Psychiatric Research, The Broad Institute of Harvard and MIT, Cambridge, Massachusetts.
authors.forename: Jordan W
authors.initials: JW
authors.lastname: Smoller
mesh_terms: D001741:Black or African American / Q000235:genetics* / Q000523:psychology / Q000706:statistics & numerical data; D000368:Aged; D003863:Depression / Q000235:genetics* / Q000523:psychology; D005260:Female; D059647:Gene-Environment Interaction; D055106:Genome-Wide Association Study / Q000706:statistics & numerical data*; D006630:Hispanic or Latino / Q000235:genetics* / Q000523:psychology / Q000706:statistics & numerical data; D006801:Humans; D008016:Life Change Events; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D057566:Self Report
keywords: depression; gene-environment interaction; genome-wide association study; social support; stressful life events