ArticlePharmacogenetics and genomics2013
Rare SERINC2 variants are specific for alcohol dependence in individuals of European descent.
Article in Pharmacogenetics and genomics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 3 of them syntheses that pooled it.
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Who cites it
16 citing papers in PubMed, 3 syntheses or guidelines pooled it, 19 citations in OpenAlex.
- Pooled it
- Exome Chip Meta-analysis Fine Maps Causal Variants and Elucidates the Genetic Architecture of Rare Coding Variants in Smoking and Alcohol Use.Biological psychiatry · 2019Pooled it
- A New Genomewide Association Meta-Analysis of Alcohol Dependence.Alcoholism, clinical and experimental research · 2015Pooled it
- A thioredoxin-Serinc2-lipid signaling axis modulates mood-related behaviors in mice.Molecular psychiatry · 2026Article
- Efficient Detection and Characterization of Targets of Natural Selection Using Transfer Learning.Molecular biology and evolution · 2025Article
- Efficient detection and characterization of targets of natural selection using transfer learning.bioRxiv : the preprint server for biology · 2025Article
- SERINC2-mediated serine metabolism promotes cervical cancer progression and drives T cell exhaustion.International journal of biological sciences · 2025Article
- Phenome-wide association studies betweenFrontiers in psychiatry · 2024Article
- Machine learning-based screening of the diagnostic genes and their relationship with immune-cell infiltration in patients with lung adenocarcinoma.Journal of thoracic disease · 2022Article
- From Beginning to End: Expanding the SERINC3 Interactome Through anBioinformatics and biology insights · 2022Article
- The Emerging Role of the Serine Incorporator Protein Family in Regulating Viral Infection.Frontiers in cell and developmental biology · 2022Review
- Diverse types of genomic evidence converge on alcohol use disorder risk genes.Journal of medical genetics · 2020Article
- A bipartite structural organization defines the SERINC family of HIV-1 restriction factors.Nature structural & molecular biology · 2020Article
- Peripheral Acid Sphingomyelinase Activity Is Associated with Biomarkers and Phenotypes of Alcohol Use and Dependence in Patients and Healthy Controls.International journal of molecular sciences · 2018Article
- Chromosomal microarray analysis in a cohort of underrepresented population identifies SERINC2 as a novel candidate gene for autism spectrum disorder.Scientific reports · 2017Article
- Analysis of population-specific pharmacogenomic variants using next-generation sequencing data.Scientific reports · 2017Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
Abstract
objectivesWe have previously reported a top-ranked risk gene [i.e., serine incorporator 2 gene (SERINC2)] for alcohol dependence in individuals of European descent by analyzing the common variants in a genome-wide association study. In the present study, we comprehensively examined the rare variants [minor allele frequency (MAF)<0.05] in the NKAIN1-SERINC2 region to confirm our previous finding. MATERIALS AND
methodsA discovery sample (1409 European-American patients with alcohol dependence and 1518 European-American controls) and a replication sample (6438 European-Australian family participants with 1645 alcohol-dependent probands) were subjected to an association analysis. A total of 39,903 individuals from 19 other cohorts with 11 different neuropsychiatric and neurological disorders served as contrast groups. The entire NKAIN1-SERINC2 region was imputed in all cohorts using the same reference panels of genotypes that included rare variants from the whole-genome sequencing data. We stringently cleaned the phenotype and genotype data, and obtained a total of about 220 single-nucleotide polymorphisms in individuals of European descent and about 450 single-nucleotide polymorphisms in the individuals of African descent with 0<MAF<0.05 for an association analysis.
resultsUsing a weighted regression analysis implemented in the program SCORE-Seq, we found a rare variant constellation across the entire NKAIN1-SERINC2 region that was associated with alcohol dependence in European-Americans (Fp: overall, P=1.8×10(-4); VT: overall, P=1.4×10(-4); Collapsing, P=6.5×10(-5)) and European-Australians (Fp: overall, P=0.028; Collapsing, P=0.025), but not in African-Americans, and not associated with any other disorder examined. Association signals in this region came mainly from SERINC2, a gene that codes for an activity-regulated protein expressed in the brain that incorporates serine into lipids. In addition, 26 individual rare variants were nominally associated with alcohol dependence in European-Americans (P<0.05). The associations of five of these rare variants that lay within SERINC2 showed region-wide significance (P<α=0.0006) and 25 associations survived correction for a false discovery rate (q<0.05). The associations of two rare variants at SERINC2 were replicated in European-Australians (P<0.05).
conclusionWe concluded that SERINC2 was a replicable and significant risk gene specific for alcohol dependence in individuals of European descent.
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