scholarly journals Genome-wide Association of Single-Nucleotide Polymorphisms With Weight Loss Outcomes After Roux-en-Y Gastric Bypass Surgery

2013 ◽  
Vol 98 (6) ◽  
pp. E1131-E1136 ◽  
Author(s):  
Erica S. Rinella ◽  
Christopher Still ◽  
Yongzhao Shao ◽  
G. Craig Wood ◽  
Xin Chu ◽  
...  
Keyword(s):  
Weight Loss ◽  
Gastric Bypass ◽  
Association Study ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Single Nucleotide ◽  
Snp Arrays ◽  
Genome Wide ◽  
Common Genetic Variants ◽  
Weight Loss Outcomes

Context: Roux-en-Y gastric bypass (RYGB) is among the most effective treatments for extreme obesity and obesity-related complications. However, despite its potential efficacy, many patients do not achieve and/or maintain sufficient weight loss. Objective: Our objective was to identify genetic factors underlying the variability in weight loss outcomes after RYGB surgery. Design: We conducted a genome-wide association study using a 2-stage phenotypic extreme study design. Setting: Patients were recruited from a comprehensive weight loss program at an integrated health system. Patients: Eighty-six obese (body mass index >35 kg/m2) patients who had the least percent excess body weight loss (%EBWL) and 89 patients who had the most %EBWL at 2 years after surgery were genotyped using Affymetrix version 6.0 single-nucleotide polymorphism (SNP) arrays. A second group from the same cohort consisting of 164 patients in the lower quartile of %EBWL and 169 from the upper quartile were selected for evaluation of candidate regions using custom SNP arrays. Intervention: We performed RYGB surgery. Main Outcome Measures: We assessed %EBWL at 2 years after RYGB and SNPs. Results: We identified 111 SNPs in the first-stage analysis whose frequencies were significantly different between 2 phenotypic extremes of weight loss (allelic χ2 test P < .0001). Linear regression of %EBWL at 2 years after surgery revealed 17 SNPs that approach P < .05 in the validation stage and cluster in or near several genes with potential biological relevance including PKHD1, HTR1A, NMBR, and IGF1R. Conclusions: This is the first genome-wide association study of weight loss response to RYGB. Variation in weight loss outcomes after RYGB may be influenced by several common genetic variants.

scholarly journals Genome-wide association study identifies 48 common genetic variants associated with handedness

2019 ◽  
Author(s):  
Gabriel Cuellar Partida ◽  
Joyce Y Tung ◽  
Nicholas Eriksson ◽  
Eva Albrecht ◽  
Fazil Aliev ◽  
...  
Keyword(s):  
Association Study ◽  
Genetic Variants ◽  
Complex Traits ◽  
Genome Wide Association Study ◽  
Genetic Correlations ◽  
Genome Wide Association ◽  
Left Handedness ◽  
Left Handed ◽  
Genome Wide ◽  
Common Genetic Variants

AbstractHandedness, a consistent asymmetry in skill or use of the hands, has been studied extensively because of its relationship with language and the over-representation of left-handers in some neurodevelopmental disorders. Using data from the UK Biobank, 23andMe and 32 studies from the International Handedness Consortium, we conducted the world’s largest genome-wide association study of handedness (1,534,836 right-handed, 194,198 (11.0%) left-handed and 37,637 (2.1%) ambidextrous individuals). We found 41 genetic loci associated with left-handedness and seven associated with ambidexterity at genome-wide levels of significance (P < 5×10−8). Tissue enrichment analysis implicated the central nervous system and brain tissues including the hippocampus and cerebrum in the etiology of left-handedness. Pathways including regulation of microtubules, neurogenesis, axonogenesis and hippocampus morphology were also highlighted. We found suggestive positive genetic correlations between being left-handed and some neuropsychiatric traits including schizophrenia and bipolar disorder. SNP heritability analyses indicated that additive genetic effects of genotyped variants explained 5.9% (95% CI = 5.8% – 6.0%) of the underlying liability of being left-handed, while the narrow sense heritability was estimated at 12% (95% CI = 7.2% – 17.7%). Further, we show that genetic correlation between left-handedness and ambidexterity is low (rg = 0.26; 95% CI = 0.08 – 0.43) implying that these traits are largely influenced by different genetic mechanisms. In conclusion, our findings suggest that handedness, like many other complex traits is highly polygenic, and that the genetic variants that predispose to left-handedness may underlie part of the association with some psychiatric disorders that has been observed in multiple observational studies.

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 Common Susceptibility Loci for Male Breast Cancer

2020 ◽  
Author(s):  
Sarah Maguire ◽  
Eleni Perraki ◽  
Katarzyna Tomczyk ◽  
Michael E Jones ◽  
Olivia Fletcher ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Association Study ◽  
Genetic Correlation ◽  
Male Breast Cancer ◽  
Genetic Basis ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Susceptibility Loci ◽  
Single Nucleotide ◽  
Genome Wide

Abstract Background The etiology of male breast cancer (MBC) is poorly understood. In particular, the extent to which the genetic basis of MBC differs from female breast cancer (FBC) is unknown. A previous genome-wide association study of MBC identified 2 predisposition loci for the disease, both of which were also associated with risk of FBC. Methods We performed genome-wide single nucleotide polymorphism genotyping of European ancestry MBC case subjects and controls in 3 stages. Associations between directly genotyped and imputed single nucleotide polymorphisms with MBC were assessed using fixed-effects meta-analysis of 1380 cases and 3620 controls. Replication genotyping of 810 cases and 1026 controls was used to validate variants with P values less than 1 × 10–06. Genetic correlation with FBC was evaluated using linkage disequilibrium score regression, by comprehensively examining the associations of published FBC risk loci with risk of MBC and by assessing associations between a FBC polygenic risk score and MBC. All statistical tests were 2-sided. Results The genome-wide association study identified 3 novel MBC susceptibility loci that attained genome-wide statistical significance (P &lt; 5 × 10–08). Genetic correlation analysis revealed a strong shared genetic basis with estrogen receptor–positive FBC. Men in the top quintile of genetic risk had a fourfold increased risk of breast cancer relative to those in the bottom quintile (odds ratio = 3.86, 95% confidence interval = 3.07 to 4.87, P = 2.08 × 10–30). Conclusions These findings advance our understanding of the genetic basis of MBC, providing support for an overlapping genetic etiology with FBC and identifying a fourfold high-risk group of susceptible men.

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