Different genes may be involved in distal and local sensitisation: a genome‐wide gene‐based association study and meta‐analysis

Abstract Response to treatment with selective serotonin reuptake inhibitors (SSRIs) varies considerably between patients. The International SSRI Pharmacogenomics Consortium (ISPC) was formed with the primary goal of identifying genetic variation that may contribute to response to SSRI treatment of major depressive disorder. A genome-wide association study of 4-week treatment outcomes, measured using the 17-item Hamilton Rating Scale for Depression (HRSD-17), was performed using data from 865 subjects from seven sites. The primary outcomes were percent change in HRSD-17 score and response, defined as at least 50% reduction in HRSD-17. Data from two prior studies, the Pharmacogenomics Research Network Antidepressant Medication Pharmacogenomics Study (PGRN-AMPS) and the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study, were used for replication, and a meta-analysis of the three studies was performed (N=2394). Although many top association signals in the ISPC analysis map to interesting candidate genes, none were significant at the genome-wide level and the associations were not replicated using PGRN-AMPS and STAR*D data. Top association results in the meta-analysis of response included single-nucleotide polymorphisms (SNPs) in the HPRTP4 (hypoxanthine phosphoribosyltransferase pseudogene 4)/VSTM5 (V-set and transmembrane domain containing 5) region, which approached genome-wide significance (P=5.03E−08) and SNPs 5’ upstream of the neuregulin-1 gene, NRG1 (P=1.20E−06). NRG1 is involved in many aspects of brain development, including neuronal maturation and variations in this gene have been shown to be associated with increased risk for mental disorders, particularly schizophrenia. Replication and functional studies of these findings are warranted.

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Genome-wide association study of early-onset bipolar I disorder in the Han Taiwanese population

Translational Psychiatry ◽

10.1038/s41398-021-01407-6 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Lawrence Shih-Hsin Wu ◽

Ming-Chyi Huang ◽

Cathy Shen-Jang Fann ◽

Hsien-Yuan Lane ◽

Chian-Jue Kuo ◽

...

Keyword(s):

Bipolar Disorder ◽

Association Study ◽

Early Onset ◽

Genome Wide Association Study ◽

Genetic Locus ◽

Meta Analysis ◽

Genome Wide Association ◽

Genome Wide ◽

A Genome ◽

Chinese Descent

AbstractThe search for susceptibility genes underlying the heterogeneous bipolar disorder has been inconclusive, often with irreproducible results. There is a hope that narrowing the phenotypes will increase the power of genetic analysis. Early-onset bipolar disorder is thought to be a genetically homogeneous subtype with greater symptom severity. We conducted a genome-wide association study (GWAS) for this subtype in bipolar I (BPI) disorder. Study participants included 1779 patients of Han Chinese descent with BPI disorder recruited by the Taiwan Bipolar Consortium. We conducted phenotype assessment using the Chinese version of the Schedules for Clinical Assessment in Neuropsychiatry and prepared a life chart with graphic depiction of lifetime clinical course for each of the BPI patient recruited. The assessment of onset age was based on this life chart with early onset defined as ≤20 years of age. We performed GWAS in a discovery group of 516 early-onset and 790 non-early-onset BPI patients, followed by a replication study in an independent group of 153 early-onset and 320 non-early-onset BPI patients and a meta-analysis with these two groups. The SNP rs11127876, located in the intron of CADM2, showed association with early-onset BPI in the discovery cohort (P = 7.04 × 10−8) and in the test of replication (P = 0.0354). After meta-analysis, this SNP was demonstrated to be a new genetic locus in CADM2 gene associated with early-onset BPI disorder (P = 5.19 × 10−8).

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A common molecular signature of patients with sickle cell disease revealed by microarray meta-analysis and a genome-wide association study

PLoS ONE ◽

10.1371/journal.pone.0199461 ◽

2018 ◽

Vol 13 (7) ◽

pp. e0199461 ◽

Cited By ~ 3

Author(s):

Cherif Ben Hamda ◽

Raphael Sangeda ◽

Liberata Mwita ◽

Ayton Meintjes ◽

Siana Nkya ◽

...

Keyword(s):

Sickle Cell Disease ◽

Association Study ◽

Sickle Cell ◽

Genome Wide Association Study ◽

Meta Analysis ◽

Genome Wide Association ◽

Molecular Signature ◽

Cell Disease ◽

Genome Wide ◽

A Genome

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Risk loci for chronic obstructive pulmonary disease: a genome-wide association study and meta-analysis

The Lancet Respiratory Medicine ◽

10.1016/s2213-2600(14)70002-5 ◽

2014 ◽

Vol 2 (3) ◽

pp. 214-225 ◽

Cited By ~ 179

Author(s):

Michael H Cho ◽

Merry-Lynn N McDonald ◽

Xiaobo Zhou ◽

Manuel Mattheisen ◽

Peter J Castaldi ◽

...

Keyword(s):

Chronic Obstructive Pulmonary Disease ◽

Association Study ◽

Pulmonary Disease ◽

Genome Wide Association Study ◽

Meta Analysis ◽

Genome Wide Association ◽

Chronic Obstructive ◽

Obstructive Pulmonary Disease ◽

Genome Wide ◽

A Genome

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A genome-wide meta-analysis uncovers six sequence variants conferring risk of vertigo

Communications Biology ◽

10.1038/s42003-021-02673-2 ◽

2021 ◽

Vol 4 (1) ◽

Author(s):

Astros Th. Skuladottir ◽

Gyda Bjornsdottir ◽

Muhammad Sulaman Nawaz ◽

Hannes Petersen ◽

Solvi Rognvaldsson ◽

...

Keyword(s):

Association Study ◽

Hearing Impairment ◽

Genome Wide Association Study ◽

Meta Analysis ◽

Genome Wide Association ◽

European Ancestry ◽

Sequence Variants ◽

Age Related ◽

Genome Wide ◽

A Genome

AbstractVertigo is the leading symptom of vestibular disorders and a major risk factor for falls. In a genome-wide association study of vertigo (Ncases = 48,072, Ncontrols = 894,541), we uncovered an association with six common sequence variants in individuals of European ancestry, including missense variants in ZNF91, OTOG, OTOGL, and TECTA, and a cis-eQTL for ARMC9. The association of variants in ZNF91, OTOGL, and OTOP1 was driven by an association with benign paroxysmal positional vertigo. Using previous reports of sequence variants associating with age-related hearing impairment and motion sickness, we found eight additional variants that associate with vertigo. Although disorders of the auditory and the vestibular system may co-occur, none of the six genome-wide significant vertigo variants were associated with hearing loss and only one was associated with age-related hearing impairment. Our results uncovered sequence variants associating with vertigo in a genome-wide association study and implicated genes with known roles in inner ear development, maintenance, and disease.

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Genome-wide association study of phenotypes measuring progression from first cocaine or opioid use to dependence reveals novel risk genes

Exploration of Medicine ◽

10.37349/emed.2020.00032 ◽

2021 ◽

Author(s):

Richard Sherva ◽

Congcong Zhu ◽

Leah Wetherill ◽

Howard J. Edenberg ◽

Emma Johnson ◽

...

Keyword(s):

Association Study ◽

Genome Wide Association Study ◽

Meta Analysis ◽

Chromosome 21 ◽

Genome Wide Association ◽

Chromosome 1 ◽

Opioid Use ◽

Discovery Sample ◽

Genome Wide ◽

A Genome

Aim: Substance use disorders (SUD) result in substantial morbidity and mortality worldwide. Opioids, and to a lesser extent cocaine, contribute to a large percentage of this health burden. Despite their high heritability, few genetic risk loci have been identified for either opioid or cocaine dependence (OD or CD, respectively). A genome-wide association study of OD and CD related phenotypes reflecting the time between first self-reported use of these substances and a first DSM-IV dependence diagnosis was conducted. Methods: Cox proportional hazards regression in a discovery sample of 6,188 African-Americans (AAs) and 6,835 European-Americans (EAs) participants in a genetic study of multiple substance dependence phenotypes were used to test for association between genetic variants and these outcomes. The top findings were tested for replication in two independent cohorts. Results: In the discovery sample, three independent regions containing variants associated with time to dependence at P < 5 x 10-8 were identified, one (rs61835088 = 1.03 x 10-8) for cocaine in the combined EA-AA meta-analysis in the gene FAM78B on chromosome 1, and two for opioids in the AA portion of the sample in intergenic regions of chromosomes 4 (rs4860439, P = 1.37 x 10-8) and 9 (rs7032521, P = 3.30 x 10-8). After meta-analysis with data from the replication cohorts, the signal at rs61835088 improved (HR = 0.87, P = 3.71 x 10-9 and an intergenic SNP on chromosome 21 (rs2825295, HR = 1.14, P = 2.57 x 10-8) that missed the significance threshold in the AA discovery sample became genome-wide significant (GWS) for CD. Conclusions: Although the two GWS variants are not in genes with obvious links to SUD biology and have modest effect sizes, they are statistically robust and show evidence for association in independent samples. These results may point to novel pathways contributing to disease progression and highlight the utility of related phenotypes to better understand the genetics of SUDs.

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