A flexible genome-wide bootstrap method that accounts for rankingand threshold-selection bias in GWAS interpretation and replication study design

2011 ◽  
Vol 30 (15) ◽  
pp. 1898-1912 ◽  
Author(s):  
Laura L. Faye ◽  
Lei Sun ◽  
Apostolos Dimitromanolakis ◽  
Shelley B. Bull
Keyword(s):  
Selection Bias ◽  
Study Design ◽  
Bootstrap Method ◽  
Replication Study ◽  
Threshold Selection ◽  
Genome Wide ◽  
Flexible Genome

scholarly journals Genome-wide association and replication study of anti-tuberculosis drugs-induced liver toxicity

BMC Genomics ◽  
2016 ◽  
Vol 17 (1) ◽  
Author(s):  
Zelalem Petros ◽  
Ming-Ta Michael Lee ◽  
Atsushi Takahashi ◽  
Yanfei Zhang ◽  
Getnet Yimer ◽  
...  
Keyword(s):  
Liver Toxicity ◽  
Replication Study ◽  
Genome Wide Association ◽  
Genome Wide

scholarly journals A genome-wide association study of antidepressant response in Koreans

2015 ◽  
Vol 5 (9) ◽  
pp. e633-e633 ◽  
Author(s):  
W Myung ◽  
J Kim ◽  
S-W Lim ◽  
S Shim ◽  
H-H Won ◽  
...  
Keyword(s):  
Association Study ◽  
Genome Wide Association Study ◽  
Antidepressant Drugs ◽  
Replication Study ◽  
Genome Wide Association ◽  
Antidepressant Response ◽  
Drug Concentrations ◽  
Genome Wide ◽  
A Genome ◽  
Stage 1

Abstract We conducted a three-stage genome-wide association study (GWAS) of response to antidepressant drugs in an ethnically homogeneous sample of Korean patients in untreated episodes of nonpsychotic unipolar depression, mostly of mature onset. Strict quality control was maintained in case selection, diagnosis, verification of adherence and outcome assessments. Analyzed cases completed 6 weeks of treatment with adequate plasma drug concentrations. The overall successful completion rate was 85.5%. Four candidate single-nucleotide polymorphisms (SNPs) on three chromosomes were identified by genome-wide search in the discovery sample of 481 patients who received one of four allowed selective serotonin reuptake inhibitor (SSRI) antidepressant drugs (Stage 1). In a focused replication study of 230 SSRI-treated patients, two of these four SNP candidates were confirmed (Stage 2). Analysis of the Stage 1 and Stage 2 samples combined (n=711) revealed GWAS significance (P=1.60 × 10-8) for these two SNP candidates, which were in perfect linkage disequilibrium. These two significant SNPs were confirmed also in a focused cross-replication study of 159 patients treated with the non-SSRI antidepressant drug mirtazapine (Stage 3). Analysis of the Stage 1, Stage 2 and Stage 3 samples combined (n=870) also revealed GWAS significance for these two SNPs, which was sustained after controlling for gender, age, number of previous episodes, age at onset and baseline severity (P=3.57 × 10-8). For each SNP, the response rate decreased (odds ratio=0.31, 95% confidence interval: 0.20–0.47) as a function of the number of minor alleles (non-response alleles). The two SNPs significantly associated with antidepressant response are rs7785360 and rs12698828 of the AUTS2 gene, located on chromosome 7 in 7q11.22. This gene has multiple known linkages to human psychological functions and neurobehavioral disorders. Rigorous replication efforts in other ethnic populations are recommended.

The Rochester Diabetic Neuropathy Study: Design, criteria for types of neuropathy, selection bias, and reproducibility of neuropathic tests

Neurology ◽  
1991 ◽  
Vol 41 (6) ◽  
pp. 799-799 ◽  
Author(s):  
P. J. Dyck ◽  
K. M. Kratz ◽  
K. A. Lehman ◽  
J. L. Karnes ◽  
L. J. Melton ◽  
...  
Keyword(s):  
Diabetic Neuropathy ◽  
Selection Bias ◽  
Study Design ◽  
Design Criteria

Replication study of 10 genes showing evidence for association with multiple sclerosis: validation of TMEM39A, IL12B and CLBL genes

2011 ◽  
Vol 18 (7) ◽  
pp. 959-965 ◽  
Author(s):  
Jezabel Varadé ◽  
Manuel Comabella ◽  
Miguel A Ortiz ◽  
Rafael Arroyo ◽  
Oscar Fernández ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Autoimmune Diseases ◽  
Association Study ◽  
Genome Wide Association Study ◽  
Susceptibility Gene ◽  
Pooled Analysis ◽  
Replication Study ◽  
Genome Wide Association ◽  
Genome Wide

Background and objectives: Ten genes previously showing different evidence of association with multiple sclerosis have been selected to validate. Methods: Eleven polymorphisms were genotyped with the iPLEX™ Sequenom in a well-powered collection of Spanish origin including 2863 multiple sclerosis cases and 2930 controls. Results: Replication extended to the following polymorphisms: PKN2 (rs305217), GTF2B (rs7538427), EPHA4 (rs1517440), YTHDF3 (rs12115114), ANKFN1 (rs17758761) and PTPRM (rs4798571), which did not reach the threshold of significance in a follow-up of the first genome-wide association study (GWAS) conducted in multiple sclerosis; TMEM39A (rs1132200), which appeared as a newly identified susceptibility gene in the same study; a gene previously reaching GWAS significance in Italy, CBLB (rs9657904); IL12B (rs6887695, rs10045431), a susceptibility gene shared by diverse autoimmune diseases and, finally, another gene showing inconclusive association with multiple sclerosis, CNR1 (rs1049353). Conclusions: Pooled analysis corroborated the effect on MS predisposition of three genes: TMEM39A [rs1132200: pM-H=0.001; ORM-H (95% CI)= 0.84 (0.75–0.93)], IL12B [rs6887695: pM-H=0.03; ORM-H (95% CI)= 1.09 (1.01–1.17)] and CBLB [rs9657904: pM-H=0.01; ORM-H (95% CI)= 0.89 (0.81–0.97)].

scholarly journals A genome‐wide association and replication study of blood pressure in Ugandan early adolescents

2019 ◽  
Vol 7 (10) ◽  
Author(s):  
Swaib A. Lule ◽  
Alexander J. Mentzer ◽  
Benigna Namara ◽  
Allan G. Muwenzi ◽  
Beatrice Nassanga ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Early Adolescents ◽  
Replication Study ◽  
Genome Wide Association ◽  
Genome Wide ◽  
A Genome

scholarly journals An evaluation of the genetic-matched pair study design using genome-wide SNP data from the European population

2009 ◽  
Vol 17 (7) ◽  
pp. 967-975 ◽  
Author(s):  
Timothy Tehua Lu ◽  
Oscar Lao ◽  
Michael Nothnagel ◽  
Olaf Junge ◽  
Sandra Freitag-Wolf ◽  
...  
Keyword(s):  
Study Design ◽  
European Population ◽  
Matched Pair ◽  
Snp Data ◽  
Genome Wide

scholarly journals Cognitive and behavioural outcome of children born after IVF at age 9 years

2019 ◽  
Vol 34 (11) ◽  
pp. 2193-2200 ◽  
Author(s):  
K R Heineman ◽  
D B Kuiper ◽  
Sla Bastide-van Gemert ◽  
M J Heineman ◽  
M Hadders-Algra
Keyword(s):  
Selection Bias ◽  
Study Design ◽  
False Negative ◽  
Small Sample ◽  
Developmental Outcome ◽  
Significant Difference ◽  
Multivariable Analyses ◽  
Laboratory Procedures

Abstract STUDY QUESTION Do ovarian stimulation (OS) and the in vitro laboratory procedures affect offsprings’ cognitive and behavioural outcome at 9 years? SUMMARY ANSWER OS and the in vitro laboratory procedures or the combination of both were not associated with cognitive and behavioural outcome at age 9 years. WHAT IS KNOWN ALREADY ART is not associated with an adverse short-term developmental outcome of the offspring, but limited knowledge is available on the offspring’s long-term neurodevelopmental condition. STUDY DESIGN, SIZE, DURATION A 9-year longitudinal, assessor-blinded, prospective follow-up study of 169 out of 215 singletons (79%) born between March 2005 and December 2006 was performed. PARTICIPANTS/MATERIALS, SETTING, METHODS Singletons born following IVF or ICSI with OS (n = 57), born after modified natural cycle IVF/ICSI (MNC-IVF/ICSI; n = 46) and born after natural conception to subfertile couples (Sub-NC; n = 66), were assessed at 9 years. This study design, with two ART groups and a subfertile reference group, allows for disentangling the effects of OS and ART procedures on developmental outcome. Cognitive outcome was evaluated with the Wechsler abbreviated scale of intelligence and the NEPSY-II. Behaviour was assessed with the child behaviour checklist (CBCL) and teacher report form (TRF). Univariable analyses and multiple linear regression models were used. MAIN RESULTS AND THE ROLE OF CHANCE There was no significant difference in intelligence quotient (IQ) scores between ART groups (mean IQ (95% CI): OS 114.8 (83.2–142.6); MNC 114.0 (90.2–140.8); Sub-NC 115.4 (87.9–141.2), P = 0.746). Multivariable analyses did not reveal a statistically significant association between ART group and total, verbal and performance IQ. CBCL and TRF scores did not differ significantly between ART groups (P = 0.090 and 0.507, respectively). Multivariable analyses did not demonstrate a statistically significant association between ART group and CBCL and TRF total, or internalising and externalising T-scores. No significant correlations between time to pregnancy (TTP)—a proxy for the severity of parental subfertility—and outcome measures were found (Spearman rho between −0.050 and 0.049, NS), which was confirmed with multivariable analyses. LIMITATIONS, REASONS FOR CAUTION The attrition rate of 21% may be considered as a limitation of the study; however, after a follow-up period of 9 years, this rate is generally considered acceptable, and there were no significant differences in background characteristics between children with and without follow-up, making an attrition-related selection bias less likely. Another limitation of the study is the relatively small sample size, which could contribute to selection bias, hamper generalizability to the ART population and lead to false negative findings as a result of underpowering. An a priori power analysis on total IQ indicated that the OS-IVF/ICSI and Sub-NC groups should contain 64 children, confirming that our study including 57 and 66 children, respectively, was slightly underpowered. WIDER IMPLICATIONS OF THE FINDINGS Our study indicated that OS and the in vitro laboratory procedures or the combination of both and TTP were not associated with cognitive and behavioural outcome at 9 years. These are reassuring results for both parents and clinicians involved in ART. STUDY FUNDING/COMPETING INTEREST(S) The study was financially supported by the University Medical Center Groningen (UMCG), two graduate schools of the UMCG (BCN and SHARE) and the Cornelia Stichting. The sponsors of the study had no role in study design, data collection, data analysis, data interpretation or writing of the report. The authors have no conflicts of interest to declare.

scholarly journals Resampling methods to reduce the selection bias in genetic effect estimation in genome-wide scans

BMC Genetics ◽  
2005 ◽  
Vol 6 (Suppl 1) ◽  
pp. S24 ◽  
Author(s):  
Long Wu ◽  
Sophia SF Lee ◽  
Haijiang Shi ◽  
Lei Sun ◽  
Shelley B Bull
Keyword(s):  
Selection Bias ◽  
Genetic Effect ◽  
Resampling Methods ◽  
Genome Wide ◽  
Effect Estimation
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