scholarly journals Genome-Wide Association Study Highlights APOH as a Novel Locus for Lipoprotein(a) Levels

2020 ◽  
Author(s):  
Mary Hoekstra ◽  
Hao Yu Chen ◽  
Jian Rong ◽  
Line Dufresne ◽  
Jie Yao ◽  
...  
Keyword(s):  
Association Study ◽  
Large Scale ◽  
Genome Wide Association Study ◽  
Meta Analysis ◽  
Genome Wide Association ◽  
European Ancestry ◽  
Linear Regression Models ◽  
Lipoprotein A ◽  
Genome Wide ◽  
A Genome

Objective: Lp(a) (lipoprotein[a]) is an independent risk factor for cardiovascular diseases and plasma levels are primarily determined by variation at the LPA locus. We performed a genome-wide association study in the UK Biobank to determine whether additional loci influence Lp(a) levels. Approach and Results: We included 293 274 White British individuals in the discovery analysis. Approximately 93 095 623 variants were tested for association with natural log-transformed Lp(a) levels using linear regression models adjusted for age, sex, genotype batch, and 20 principal components of genetic ancestry. After quality control, 131 independent variants were associated at genome-wide significance (P ≤5×10 -8 ). In addition to validating previous associations at LPA , APOE , and CETP , we identified a novel variant at the APOH locus, encoding β2GPI (beta2-glycoprotein I). The APOH variant rs8178824 was associated with increased Lp(a) levels (β [95% CI] [ln nmol/L], 0.064 [0.047–0.081]; P =2.8×10 -13 ) and demonstrated a stronger effect after adjustment for variation at the LPA locus (β [95% CI] [ln nmol/L], 0.089 [0.076–0.10]; P =3.8×10 -42 ). This association was replicated in a meta-analysis of 5465 European-ancestry individuals from the Framingham Offspring Study and Multi-Ethnic Study of Atherosclerosis (β [95% CI] [ln mg/dL], 0.16 [0.044–0.28]; P =0.0071). Conclusions: In a large-scale genome-wide association study of Lp(a) levels, we identified APOH as a novel locus for Lp(a) in individuals of European ancestry. Additional studies are needed to determine the precise role of β2GPI in influencing Lp(a) levels as well as its potential as a therapeutic target.

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

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.

scholarly journals Genome-wide association study identifies locus at chromosome 2q32.1 associated with syncope and collapse

2019 ◽  
Vol 116 (1) ◽  
pp. 138-148 ◽  
Author(s):  
Katra Hadji-Turdeghal ◽  
Laura Andreasen ◽  
Christian M Hagen ◽  
Gustav Ahlberg ◽  
Jonas Ghouse ◽  
...  
Keyword(s):  
Association Study ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
European Ancestry ◽  
Psychiatric Research ◽  
Carrier Status ◽  
Genome Wide ◽  
Common Genetic Variants ◽  
A Genome ◽  
Significant Locus

Abstract Aims Syncope is a common condition associated with frequent hospitalization or visits to the emergency department. Family aggregation and twin studies have shown that syncope has a heritable component. We investigated whether common genetic variants predispose to syncope and collapse. Methods and results We used genome-wide association data on syncope on 408 961 individuals with European ancestry from the UK Biobank study. In a replication study, we used the Integrative Psychiatric Research Consortium (iPSYCH) cohort (n = 86 189), to investigate the risk of incident syncope stratified by genotype carrier status. We report on a genome-wide significant locus located on chromosome 2q32.1 [odds ratio = 1.13, 95% confidence interval (CI) 1.10–1.17, P = 5.8 × 10−15], with lead single nucleotide polymorphism rs12465214 in proximity to the gene zinc finger protein 804a (ZNF804A). This association was also shown in the iPSYCH cohort, where homozygous carriers of the C allele conferred an increased hazard ratio (1.30, 95% CI 1.15–1.46, P = 1.68 × 10−5) of incident syncope. Quantitative polymerase chain reaction analysis showed ZNF804A to be expressed most abundantly in brain tissue. Conclusion We identified a genome-wide significant locus (rs12465214) associated with syncope and collapse. The association was replicated in an independent cohort. This is the first genome-wide association study to associate a locus with syncope and collapse.

scholarly journals A genome-wide association study meta-analysis of clinical fracture in 10,012 African American women

Bone Reports ◽  
2016 ◽  
Vol 5 ◽  
pp. 233-242 ◽  
Author(s):  
Kira C. Taylor ◽  
Daniel S. Evans ◽  
Digna R. Velez Edwards ◽  
Todd L. Edwards ◽  
Tamar Sofer ◽  
...  
Keyword(s):  
African American ◽  
Association Study ◽  
African American Women ◽  
Genome Wide Association Study ◽  
Meta Analysis ◽  
Genome Wide Association ◽  
American Women ◽  
Clinical Fracture ◽  
Genome Wide ◽  
A Genome

Abstract 051: Genome-wide Association Study Identifies 12 Loci for Habitual Consumption of Bitter and Sweet Beverages

Circulation ◽  
2018 ◽  
Vol 137 (suppl_1) ◽  
Author(s):  
Victor W Zhong ◽  
Sandra Sanchez-Roige ◽  
Peter Kraft ◽  
Rob M Van Dam ◽  
Daniel I Chasman ◽  
...  
Keyword(s):  
Chronic Disease ◽  
Association Study ◽  
Genome Wide Association Study ◽  
Genetic Model ◽  
Taste Perception ◽  
Genome Wide Association ◽  
European Ancestry ◽  
Multiple Snps ◽  
Genome Wide ◽  
A Genome

Introduction: Widely consumed beverages (e.g., soft drinks, coffee, tea) are critical sources of energy, added sugar and phytochemicals and are associated with obesity and chronic disease. Taste perception and preferences are highly heritable and strong determinants of food and beverage choice. We aimed to identify novel loci underlying habitual bitter and sweet beverage intake. Methods: We performed a genome-wide association study (GWAS) of self-reported bitter and sweet beverage intake in participants of European ancestry in the UK Biobank. Diet was assessed via multiple 24-h diet recalls (n=84703, subset) or questionnaire (n=335909, all). Bitter beverage intake was the sum of coffee, tea and grapefruit juice. Sweet beverage intake was the sum of artificially and sugar sweetened beverages and other fruit juice. Multivariable linear regression under an additive genetic model was applied. GW-significant (P < 5х10 -8 ) SNPs were followed-up for replication in independent studies of European ancestry. Results: Multiple SNPs spanning 11 loci were associated with bitter beverage intake (P <5х10 -8 , Table 1), and at least 5 of them reflected the caffeine content of coffee and tea. Multiple SNPs in the obesity candidate gene FTO were associated with sweet beverage intake (P <5х10 -8 ). The effect size per allele ranged from 0.02 to 0.2 cup per day. Loci in/near AHR, CYP1A2, and FTO were associated with both bitter and sweet beverage intake but in opposite directions. Replication efforts are ongoing. So far, associations at all loci, except 1q25.2 and 2q36.2, were replicated (P range: 0.04 to 1.8x10 -8 ) in independent studies (n=17322) which provided 80% power for replicating 8 of these 12 loci at P=0.05. Conclusions: Loci linked to caffeine metabolism and obesity predisposition rather than taste are major determinants of beverage intake. These and other identified loci have been linked to chronic disease and risk factors, suggesting causal or pleiotropic effects. Our findings have potential public health and methodological implications.

scholarly journals The International SSRI Pharmacogenomics Consortium (ISPC): a genome-wide association study of antidepressant treatment response

2015 ◽  
Vol 5 (4) ◽  
pp. e553-e553 ◽  
Author(s):  
J M Biernacka ◽  
K Sangkuhl ◽  
G Jenkins ◽  
R M Whaley ◽  
P Barman ◽  
...  
Keyword(s):  
Association Study ◽  
Selective Serotonin Reuptake Inhibitors ◽  
Genome Wide Association Study ◽  
Transmembrane Domain ◽  
Meta Analysis ◽  
Genome Wide Association ◽  
Research Network ◽  
Genome Wide ◽  
A Genome ◽  
Increased Risk

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.

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

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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