Diego A Forero1, Sandra López-León2, Hyoung Doo Shin3, Byung Lae Park4, Dai-Jin Kim5. 1. Laboratory of NeuroPsychiatric Genetics, Biomedical Sciences Research Group, School of Medicine, Universidad Antonio Nariño, Bogotá, Colombia. Electronic address: diego.forero@uan.edu.co. 2. Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA. 3. Laboratory of Genomic Diversity, Department of Life Science, Sogang University, Seoul, Republic of Korea. 4. Department of Genetic Epidemiology, SNP Genetics Inc., Seoul, Republic of Korea. 5. Department of Psychiatry, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
Abstract
BACKGROUND: Alcohol-related problems have a large impact on human health, accounting for around 4% of deaths and 4.5% of disability-adjusted life-years around the world. Genetic factors could explain a significant fraction of the risk for alcohol dependence (AD). Recent meta-analyses have found significant pooled odds ratios (ORs) for variants in the ADH1B, ADH1C, DRD2 and HTR2A genes. METHODS: In the present study, we carried out a meta-analysis of common variants in 6 candidate genes involved in neurotransmission and neuroplasticity: BDNF, DRD1, DRD3, DRD4, GRIN2B and MAOA. We carried out a systematic search for published association studies that analyzed the genes of interest. Relevant articles were retrieved and demographic and genetic data were extracted. Pooled ORs were calculated using a random-effects model using the Meta-Analyst program. Dominant, recessive and allelic models were tested and analyses were also stratified by ethnicity. RESULTS: Forty two published studies were included in the current meta-analysis: BDNF-rs6265 (nine studies), DRD1-rs4532 (four studies), DRD3-rs6280 (eleven studies), DRD4-VNTR (seven studies), GRIN2B-rs1806201 (three studies) and MAOA-uVNTR (eight studies). We did not find significant pooled ORs for any of the six genes, under different models and stratifying for ethnicity. CONCLUSIONS: In terms of the number of candidate genes included, this is one of the most comprehensive meta-analyses for genetics of AD. Pooled ORs did not support consistent associations with any of the six candidate genes tested. Future studies of novel genes of functional relevance and meta-analyses of quantitative endophenotypes could identify further susceptibility molecular factors for AD.
BACKGROUND:Alcohol-related problems have a large impact on human health, accounting for around 4% of deaths and 4.5% of disability-adjusted life-years around the world. Genetic factors could explain a significant fraction of the risk for alcohol dependence (AD). Recent meta-analyses have found significant pooled odds ratios (ORs) for variants in the ADH1B, ADH1C, DRD2 and HTR2A genes. METHODS: In the present study, we carried out a meta-analysis of common variants in 6 candidate genes involved in neurotransmission and neuroplasticity: BDNF, DRD1, DRD3, DRD4, GRIN2B and MAOA. We carried out a systematic search for published association studies that analyzed the genes of interest. Relevant articles were retrieved and demographic and genetic data were extracted. Pooled ORs were calculated using a random-effects model using the Meta-Analyst program. Dominant, recessive and allelic models were tested and analyses were also stratified by ethnicity. RESULTS: Forty two published studies were included in the current meta-analysis: BDNF-rs6265 (nine studies), DRD1-rs4532 (four studies), DRD3-rs6280 (eleven studies), DRD4-VNTR (seven studies), GRIN2B-rs1806201 (three studies) and MAOA-uVNTR (eight studies). We did not find significant pooled ORs for any of the six genes, under different models and stratifying for ethnicity. CONCLUSIONS: In terms of the number of candidate genes included, this is one of the most comprehensive meta-analyses for genetics of AD. Pooled ORs did not support consistent associations with any of the six candidate genes tested. Future studies of novel genes of functional relevance and meta-analyses of quantitative endophenotypes could identify further susceptibility molecular factors for AD.
Authors: Erinaldo Ubirajara Damasceno Dos Santos; Elaine Bandeira Cavalcanti Duarte; Laura Maria Ramos Miranda; Andore Guescel C Asano; Nadja Maria Jorge Asano; Maria de Mascena Diniz Maia; Paulo Roberto Eleutério de Souza Journal: Neuromolecular Med Date: 2019-05-22 Impact factor: 3.843
Authors: Diana R Samek; Jennifer Bailey; Karl G Hill; Sylia Wilson; Susanne Lee; Margaret A Keyes; Marina Epstein; Andrew Smolen; Michael Miller; Ken C Winters; J David Hawkins; Richard F Catalano; William G Iacono; Matt McGue Journal: Behav Genet Date: 2016-07-21 Impact factor: 2.805
Authors: Diego A Forero; Yeimy González-Giraldo; Catalina López-Quintero; Luis J Castro-Vega; George E Barreto; George Perry Journal: Exp Gerontol Date: 2016-01-07 Impact factor: 4.032
Authors: R Cervera-Juanes; L J Wilhem; B Park; R Lee; J Locke; C Helms; S Gonzales; G Wand; S R Jones; K A Grant; B Ferguson Journal: Mol Psychiatry Date: 2015-07-07 Impact factor: 15.992
Authors: Cheryl Reed; Harue Baba; Zhen Zhu; Jason Erk; John R Mootz; Nicholas M Varra; Robert W Williams; Tamara J Phillips Journal: Front Pharmacol Date: 2018-01-22 Impact factor: 5.810