scholarly journals Analysis of secondary phenotypes in multigroup association studies

Biometrics ◽  
2019 ◽  
Vol 76 (2) ◽  
pp. 606-618
Author(s):  
Fan Zhou ◽  
Haibo Zhou ◽  
Tengfei Li ◽  
Hongtu Zhu
Keyword(s):  
Association Studies ◽  
Secondary Phenotypes

scholarly journals Robust analysis of secondary phenotypes in case-control genetic association studies

2016 ◽  
Vol 35 (23) ◽  
pp. 4226-4237 ◽  
Author(s):  
Chuanhua Xing ◽  
Janice M. McCarthy ◽  
Josée Dupuis ◽  
L. Adrienne Cupples ◽  
James B. Meigs ◽  
...  
Keyword(s):  
Genetic Association ◽  
Association Studies ◽  
Genetic Association Studies ◽  
Case Control ◽  
Robust Analysis ◽  
Secondary Phenotypes

scholarly journals A multi-locus genetic association test for a dichotomous trait and its secondary phenotype

2016 ◽  
Vol 27 (5) ◽  
pp. 1464-1475
Author(s):  
Han Zhang ◽  
Colin O Wu ◽  
Yifan Yang ◽  
Sonja I Berndt ◽  
Stephen J Chanock ◽  
...  
Keyword(s):  
Genetic Association ◽  
Genome Wide Association Study ◽  
Association Studies ◽  
Random Effect ◽  
Random Effect Model ◽  
Genetic Effect ◽  
Testing Procedures ◽  
A Genome ◽  
Secondary Phenotypes ◽  
Secondary Phenotype

Genetic association studies often collect information on secondary phenotypes related to the primary disease status. In many situations, the secondary phenotypes are only measured in subjects with the disease condition. It would be advantageous to model the primary trait and the secondary phenotype together if they share certain level of genetic heritability. We propose a family of multi-locus testing procedures to detect the composite association between a set of genetic markers and two traits (the primary trait and a secondary phenotype), in order to identify genes influencing both traits. The proposed test is derived from a random effect model with two variance components, with each presenting the genetic effect on one trait, and incorporates a model selection procedure for seeking the optimal model to represent the two sources of genetic effects. We conduct simulation studies to evaluate performance of the proposed procedure and apply the method to a genome-wide association study of prostate cancer with the Gleason score as the secondary phenotype.

scholarly journals A comprehensive survey of genetic variation in 20,691 subjects from four large cohorts

2016 ◽  
Author(s):  
Sara Lindström ◽  
Stephanie Loomis ◽  
Constance Turman ◽  
Hongyan Huang ◽  
Jinyan Huang ◽  
...  
Keyword(s):  
Association Studies ◽  
Health Study ◽  
Genome Wide Association Studies ◽  
Significance Level ◽  
Common Reference ◽  
Data Merging ◽  
Multiple Exposures ◽  
Comprehensive Survey ◽  
Study Participants ◽  
Secondary Phenotypes

ABSTRACTThe Nurses’ Health Study (NHS), Nurses’ Health Study II (NHSII), Health Professionals Follow Up Study (HPFS) and the Physicians Health Study (PHS) have collected detailed longitudinal data on multiple exposures and traits for approximately 310,000 study participants over the last 35 years. Over 160,000 study participants across the cohorts have donated a DNA sample and to date, 20,691 subjects have been genotyped as part of genome-wide association studies (GWAS) of twelve primary outcomes. However, these studies utilized six different GWAS arrays making it difficult to conduct analyses of secondary phenotypes or share controls across studies. To allow for secondary analyses of these data, we have created three new datasets merged by platform family and performed imputation using a common reference panel, the 1,000 Genomes Phase I release. Here, we describe the methodology behind the data merging and imputation and present imputation quality statistics and association results from two GWAS of secondary phenotypes (body mass index (BMI) and venous thromboembolism (VTE)).We observed the strongest BMI association for the FTO SNP rs55872725 (β=0.45, p=3.48×10−22), and using a significance level of p=0.05, we replicated 19 out of 32 known BMI SNPs. For VTE, we observed the strongest association for the rs2040445 SNP (OR=2.17, 95% CI: 1.79-2.63, p=2.70×10−15), located downstream of F5 and also observed significant associations for the known ABO and F11 regions. This pooled resource can be used to maximize power in GWAS of phenotypes collected across the cohorts and for studying gene-environment interactions as well as rare phenotypes and genotypes.

Serotonergic Genes and Suicidality

Crisis ◽  
2001 ◽  
Vol 22 (2) ◽  
pp. 54-60 ◽  
Author(s):  
Lisheng Du ◽  
Gabor Faludi ◽  
Miklos Palkovits ◽  
David Bakish ◽  
Pavel D. Hrdina
Keyword(s):  
Suicidal Ideation ◽  
Suicidal Behavior ◽  
Tryptophan Hydroxylase ◽  
Association Studies ◽  
Receptor Gene ◽  
Brain Regions ◽  
Depressive Illness ◽  
Control Group ◽  
Serotonergic Activity ◽  
Completed Suicide

Summary: Several lines of evidence indicate that abnormalities in the functioning of the central serotonergic system are involved in the pathogenesis of depressive illness and suicidal behavior. Studies have shown that the number of brain and platelet serotonin transporter binding sites are reduced in patients with depression and in suicide victims, and that the density of 5-HT2A receptors is increased in brain regions of depressed in suicide victims and in platelets of depressed suicidal patients. Genes that code for proteins, such as tryptophan hydroxylase, 5-HT transporter, and 5-HT2A receptor, involved in regulating serotonergic neurotransmission, have thus been major candidate genes for association studies of suicide and suicidal behavior. Recent studies by our group and by others have shown that genetic variations in the serotonin-system-related genes might be associated with suicidal ideation and completed suicide. We have shown that the 102 C allele in 5-HT2A receptor gene was significantly associated with suicidal ideation (χ2 = 8.5, p < .005) in depressed patients. Patients with a 102 C/C genotype had a significantly higher mean HAMD item #3 score (indication of suicidal ideation) than T/C or T/T genotype patients. Our results suggest that the 102T/C polymorphism in 5-HT2A receptor gene is primarily associated with suicidal ideation in patients with major depression and not with depression itself. We also found that the 5-HT transporter gene S/L polymorphism was significantly associated with completed suicide. The frequency of the L/L genotype in depressed suicide victims was almost double of that found in control group (48.6% vs. 26.2%). The odds ratio for the L allele was 2.1 (95% CI 1.2-3.7). The association between polymorphism in serotonergic genes and suicidality supports the hypothesis that genetic factors can modulate suicide risk by influencing serotonergic activity.

TLR1 and PRKAA1 Gene Polymorphisms in the Development of Atrophic Gastritis and Gastric Cancer

2018 ◽  
Vol 27 (4) ◽  
pp. 363-369 ◽  
Author(s):  
Gintare Dargiene ◽  
Greta Streleckiene ◽  
Jurgita Skieceviciene ◽  
Marcis Leja ◽  
Alexander Link ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Atrophic Gastritis ◽  
Genetic Polymorphisms ◽  
Association Studies ◽  
Control Group ◽  
Similar Distribution ◽  
Genome Wide Association Studies ◽  
Increased Risk ◽  
Infection Susceptibility ◽  
H Pylori

Background & Aims: Previous genome-wide association studies showed that genetic polymorphisms in toll-like receptor 1 (TLR1) and protein kinase AMP-activated alpha 1 catalytic subunit (PRKAA1) genes were associated with gastric cancer (GC) or increased Helicobacter pylori (H. pylori) infection susceptibility. The aim of this study was to evaluate the association between TLR1 and PRKAA1 genes polymorphisms and H.pylori infection, atrophic gastritis (AG) or GC in the European population.Methods: Single-nucleotide polymorphisms (SNPs) were analysed in 511 controls, 340 AG patients and 327 GC patients. TLR1 C>T (rs4833095) and PRKAA1 C>T (rs13361707) were genotyped by the real-time polymerase chain reaction. H. pylori status was determined by testing for anti-H. pylori IgG antibodies in the serum.Results: The study included 697 (59.2%) H. pylori positive and 481 (40.8%) H. pylori negative cases. We observed similar distribution of TLR1 and PRKAA1 alleles and genotypes in H. pylori positive and negative cases. TLR1 and PRKAA1 SNPs were not linked with the risk of AG. TC genotype of TLR1 gene was more prevalent in GC patients compared to the control group (29.7% and 22.3% respectively, p=0.002). Carriers of TC genotype had a higher risk of GC (aOR=1.89, 95% CI: 1.26–2.83, p=0.002). A similar association was observed in a dominant inheritance model for TLR1 gene SNP, where comparison of CC+TC vs. TT genotypes showed an increased risk of GC (aOR=1.86, 95% CI: 1.26–2.75, p=0.002). No association between genetic polymorphism in PRKAA1 gene and GC was observed.Conclusions: TLR1 rs4833095 SNP was associated with an increased risk of GC in a European population, while PRKAA1 rs13361707 genetic variant was not linked with GC. Both genetic polymorphisms were not associated with H. pylori infection susceptibility or the risk of AG.

Sign in / Sign up

Export Citation Format

Share Document