Identifying genetic predictors of depression risk: 5-HTTLPR and BDNF Val66Met polymorphisms are associated with rumination and co-rumination in adolescents

Background: Despite research supporting moderate heritability of depression, efforts to replicate candidate gene associations to depression have yielded inconsistent results. We tested whether Val66Met and 5-HTTLPR exhibit utility as genetic markers of depression risk, testing for replicable associa...

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Main Authors: Lindsey B Stone, John E McGeary, Rohan H. C. Palmer, Brandon E Gibb
Format: Article
Language:English
Published: Frontiers Media S.A. 2013-11-01
Series:Frontiers in Genetics
Subjects:
Online Access:http://journal.frontiersin.org/Journal/10.3389/fgene.2013.00246/full
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author Lindsey B Stone
Lindsey B Stone
John E McGeary
John E McGeary
John E McGeary
Rohan H. C. Palmer
Rohan H. C. Palmer
Brandon E Gibb
author_facet Lindsey B Stone
Lindsey B Stone
John E McGeary
John E McGeary
John E McGeary
Rohan H. C. Palmer
Rohan H. C. Palmer
Brandon E Gibb
author_sort Lindsey B Stone
collection DOAJ
description Background: Despite research supporting moderate heritability of depression, efforts to replicate candidate gene associations to depression have yielded inconsistent results. We tested whether Val66Met and 5-HTTLPR exhibit utility as genetic markers of depression risk, testing for replicable associations to cognitive and interpersonal endophenotypes of depression (rumination and co-rumination), and further exploring developmental and sex moderation.Method: In Study I, 228 youth (ages 8-14) of mothers with or without a history of MDD during the child’s lifetime were recruited from the community. Replication tests were carried out in Study II, a sample of 87 youth with similar recruitment.Results: In Study I, the Val66Met SNP was associated with rumination in adolescents, but not children, such that adolescents homozygous for the Val allele reported higher rumination levels. Further, a cumulative genetic score (Val66Val and 5-HTTLPR) predicted higher levels of co-rumination, specifically among adolescent girls. Both genetic associations maintained significance after covarying for current depressive symptomology, and the other endophenotype. Finally, both genetic associations exhibited similar effect sizes in Study II, although results did not reach statistical significance.Conclusions: Results replicate a previously reported association between the BDNF Val allele and rumination in adolescents, and provide preliminary support for a cumulative genetic score predictive of co-rumination in adolescent girls. The current study indicates that candidate genes may demonstrate utility as consistent genetic markers of depression risk when focused on specific phenotypes, and supports the need to explore potential differential effects of developmental stage and sex. However, given the small sample sizes and possibility of chance findings, these results should be interpreted with caution pending replication.
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spelling doaj.art-c7970ced99c343d4a657fff636865ed92022-12-22T03:44:50ZengFrontiers Media S.A.Frontiers in Genetics1664-80212013-11-01410.3389/fgene.2013.0024656792Identifying genetic predictors of depression risk: 5-HTTLPR and BDNF Val66Met polymorphisms are associated with rumination and co-rumination in adolescentsLindsey B Stone0Lindsey B Stone1John E McGeary2John E McGeary3John E McGeary4Rohan H. C. Palmer5Rohan H. C. Palmer6Brandon E Gibb7Binghamton UniversityAlpert Medical School at Brown UniversityProvidence VA Medical CenterRhode Island HospitalAlpert Medical School at Brown UniversityRhode Island HospitalAlpert Medical School at Brown UniversityBinghamton UniversityBackground: Despite research supporting moderate heritability of depression, efforts to replicate candidate gene associations to depression have yielded inconsistent results. We tested whether Val66Met and 5-HTTLPR exhibit utility as genetic markers of depression risk, testing for replicable associations to cognitive and interpersonal endophenotypes of depression (rumination and co-rumination), and further exploring developmental and sex moderation.Method: In Study I, 228 youth (ages 8-14) of mothers with or without a history of MDD during the child’s lifetime were recruited from the community. Replication tests were carried out in Study II, a sample of 87 youth with similar recruitment.Results: In Study I, the Val66Met SNP was associated with rumination in adolescents, but not children, such that adolescents homozygous for the Val allele reported higher rumination levels. Further, a cumulative genetic score (Val66Val and 5-HTTLPR) predicted higher levels of co-rumination, specifically among adolescent girls. Both genetic associations maintained significance after covarying for current depressive symptomology, and the other endophenotype. Finally, both genetic associations exhibited similar effect sizes in Study II, although results did not reach statistical significance.Conclusions: Results replicate a previously reported association between the BDNF Val allele and rumination in adolescents, and provide preliminary support for a cumulative genetic score predictive of co-rumination in adolescent girls. The current study indicates that candidate genes may demonstrate utility as consistent genetic markers of depression risk when focused on specific phenotypes, and supports the need to explore potential differential effects of developmental stage and sex. However, given the small sample sizes and possibility of chance findings, these results should be interpreted with caution pending replication.http://journal.frontiersin.org/Journal/10.3389/fgene.2013.00246/fullDepression5-HTTLPRruminationBDNF Val66Metco-rumination
spellingShingle Lindsey B Stone
Lindsey B Stone
John E McGeary
John E McGeary
John E McGeary
Rohan H. C. Palmer
Rohan H. C. Palmer
Brandon E Gibb
Identifying genetic predictors of depression risk: 5-HTTLPR and BDNF Val66Met polymorphisms are associated with rumination and co-rumination in adolescents
Frontiers in Genetics
Depression
5-HTTLPR
rumination
BDNF Val66Met
co-rumination
title Identifying genetic predictors of depression risk: 5-HTTLPR and BDNF Val66Met polymorphisms are associated with rumination and co-rumination in adolescents
title_full Identifying genetic predictors of depression risk: 5-HTTLPR and BDNF Val66Met polymorphisms are associated with rumination and co-rumination in adolescents
title_fullStr Identifying genetic predictors of depression risk: 5-HTTLPR and BDNF Val66Met polymorphisms are associated with rumination and co-rumination in adolescents
title_full_unstemmed Identifying genetic predictors of depression risk: 5-HTTLPR and BDNF Val66Met polymorphisms are associated with rumination and co-rumination in adolescents
title_short Identifying genetic predictors of depression risk: 5-HTTLPR and BDNF Val66Met polymorphisms are associated with rumination and co-rumination in adolescents
title_sort identifying genetic predictors of depression risk 5 httlpr and bdnf val66met polymorphisms are associated with rumination and co rumination in adolescents
topic Depression
5-HTTLPR
rumination
BDNF Val66Met
co-rumination
url http://journal.frontiersin.org/Journal/10.3389/fgene.2013.00246/full
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