Dataset Information

Association of Genetic Variation at AQP4 Locus with Vascular Depression.

ABSTRACT: Despite its substantial clinical importance, specific genetic variants associated with depression have not yet been identified. We sought to identify genetic variants associated with depression by (a) focusing on a more homogenous subsample (vascular depression) and (b) applying a three-stage approach. First, we contacted 730 participants with a confirmed atherosclerotic disease (coronary artery disease) from a population-based study population (German Myocardial Infarction Family Study IV) for psychiatric assessment with the Mini International Neuropsychiatric Interview. Second, we genotyped these patients using genome-wide single nucleotide polymorphism (SNP) arrays. Third, we characterized the SNP via in-silico analysis. The final sample consisted of 342 patients (78.3% male, age = 63.2 ± 9.9 years), 22.8% with a severe depressive disorder. Variant rs528732638 on chromosome 18q11.2 was a genome-wide significant variant and was associated with 3.6-fold increase in the odds of lifetime depression. The locus belongs to a linkage disequilibrium block showing expression quantitative trait loci effects on three putative cis-regulated genes, including the aquaporin 4 (AQP4) locus. AQP4 is already known to mediate the formation of ischemic edema in the brain and heart, increasing the size and extent of resulting lesions. Our findings indicate that AQP4 may also play a role in the etiopathology of vascular depression.

SUBMITTER: Westermair AL

PROVIDER: S-EPMC6316852 | biostudies-other | 2018 Dec

REPOSITORIES: biostudies-other

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Association of Genetic Variation at <i>AQP4</i> Locus with Vascular Depression.

Westermair Anna L AL Munz Matthias M Schaich Anja A Nitsche Stefan S Willenborg Bastian B Muñoz Venegas Loreto M LM Willenborg Christina C Schunkert Heribert H Schweiger Ulrich U Erdmann Jeanette J

Biomolecules 20181205 4

Despite its substantial clinical importance, specific genetic variants associated with depression have not yet been identified. We sought to identify genetic variants associated with depression by (a) focusing on a more homogenous subsample (vascular depression) and (b) applying a three-stage approach. First, we contacted 730 participants with a confirmed atherosclerotic disease (coronary artery disease) from a population-based study population (German Myocardial Infarction Family Study IV) for ...[more]

PMID: 30563176

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Project description:ImportanceKeratoconus is a condition in which the cornea progressively thins and protrudes in a conical shape, severely affecting refraction and vision. It is a major indication for corneal transplant. To discover new genetic loci associated with keratoconus and better understand the causative mechanism of this disease, we performed a genome-wide association study on patients with keratoconus.ObjectiveTo identify genetic susceptibility regions for keratoconus in the human genome.Design, setting, and participantsThis study was conducted with data from eye clinics in Australia, the United States, and Northern Ireland. The discovery cohort of individuals with keratoconus and control participants from Australia was genotyped using the Illumina HumanCoreExome single-nucleotide polymorphism array. After quality control and data cleaning, genotypes were imputed against the 1000 Genomes Project reference panel (phase III; version 5), and association analyses were completed using PLINK version 1.90. Single-nucleotide polymorphisms with P < 1.00 × 10-6 were assessed for replication in 3 additional cohorts. Control participants were drawn from the cohorts of the Blue Mountains Eye Study and a previous study of glaucoma. Replication cohorts were from a previous keratoconus genome-wide association study data set from the United States, a cohort of affected and control participants from Australia and Northern Ireland, and a case-control cohort from Victoria, Australia. Data were collected from January 2006 to March 2019.Main outcomes and measuresAssociations between keratoconus and 6 252 612 genetic variants were estimated using logistic regression after adjusting for ancestry using the first 3 principal components.ResultsThe discovery cohort included 522 affected individuals and 655 control participants, while the replication cohorts included 818 affected individuals (222 from the United States, 331 from Australia and Northern Ireland, and 265 from Victoria, Australia) and 3858 control participants (2927 from the United States, 229 from Australia and Northern Ireland, and 702 from Victoria, Australia). Two novel loci reached genome-wide significance (defined as P < 5.00 × 10-8), with a P value of 7.46 × 10-9 at rs61876744 in patatin-like phospholipase domain-containing 2 gene (PNPLA2) on chromosome 11 and a P value of 6.35 × 10-12 at rs138380, 2.2 kb upstream of casein kinase I isoform epsilon gene (CSNK1E) on chromosome 22. One additional locus was identified with a P value less than 1.00 × 10-6 in mastermind-like transcriptional coactivator 2 (MAML2) on chromosome 11 (P = 3.91 × 10-7). The novel locus in PNPLA2 reached genome-wide significance in an analysis of all 4 cohorts (P = 2.45 × 10-8).Conclusions and relevanceIn this relatively large keratoconus genome-wide association study, we identified a genome-wide significant locus for keratoconus in the region of PNPLA2 on chromosome 11.

Dataset Information

Association of Genetic Variation at AQP4 Locus with Vascular Depression.

Publications

Association of Genetic Variation at <i>AQP4</i> Locus with Vascular Depression.

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