Incorporating Functional Genomic Information in Genetic Association Studies Using an Empirical Bayes Approach

Abstract Hi-C experiments have become very popular for studying the 3D genome structure in recent years. Identification of long-range chromosomal interaction, i.e., peak detection, is crucial for Hi-C data analysis. But it remains a challenging task due to the inherent high dimensionality, sparsity and the over-dispersion of the Hi-C count data matrix. We propose EBHiC, an empirical Bayes approach for peak detection from Hi-C data. The proposed framework provides flexible over-dispersion modeling by explicitly including the “true” interaction intensities as latent variables. To implement the proposed peak identification method (via the empirical Bayes test), we estimate the overall distributions of the observed counts semiparametrically using a Smoothed Expectation Maximization algorithm, and the empirical null based on the zero assumption. We conducted extensive simulations to validate and evaluate the performance of our proposed approach and applied it to real datasets. Our results suggest that EBHiC can identify better peaks in terms of accuracy, biological interpretability, and the consistency across biological replicates. The source code is available on Github (https://github.com/QiZhangStat/EBHiC).

Download Full-text

Fine scale human genetic structure in three regions of Cameroon reveals episodic diversifying selection

Scientific Reports ◽

10.1038/s41598-020-79124-1 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Kevin K. Esoh ◽

Tobias O. Apinjoh ◽

Steven G. Nyanjom ◽

Ambroise Wonkam ◽

Emile R. Chimusa ◽

...

Keyword(s):

Genetic Structure ◽

Ethnic Groups ◽

Genetic Association ◽

Association Studies ◽

Genetic Association Studies ◽

Genomic Region ◽

Sub Saharan Africa ◽

Genome Wide Association Studies ◽

Fine Scale ◽

Sub Saharan

AbstractInferences from genetic association studies rely largely on the definition and description of the underlying populations that highlight their genetic similarities and differences. The clustering of human populations into subgroups (population structure) can significantly confound disease associations. This study investigated the fine-scale genetic structure within Cameroon that may underlie disparities observed with Cameroonian ethnicities in malaria genome-wide association studies in sub-Saharan Africa. Genotype data of 1073 individuals from three regions and three ethnic groups in Cameroon were analyzed using measures of genetic proximity to ascertain fine-scale genetic structure. Model-based clustering revealed distinct ancestral proportions among the Bantu, Semi-Bantu and Foulbe ethnic groups, while haplotype-based coancestry estimation revealed possible longstanding and ongoing sympatric differentiation among individuals of the Foulbe ethnic group, and their Bantu and Semi-Bantu counterparts. A genome scan found strong selection signatures in the HLA gene region, confirming longstanding knowledge of natural selection on this genomic region in African populations following immense disease pressure. Signatures of selection were also observed in the HBB gene cluster, a genomic region known to be under strong balancing selection in sub-Saharan Africa due to its co-evolution with malaria. This study further supports the role of evolution in shaping genomes of Cameroonian populations and reveals fine-scale hierarchical structure among and within Cameroonian ethnicities that may impact genetic association studies in the country.

Download Full-text

Patterns of linkage disequilibrium atPARK16may explain variances in genetic association studies

Movement Disorders ◽

10.1002/mds.26176 ◽

2015 ◽

Vol 30 (10) ◽

pp. 1335-1342 ◽

Cited By ~ 6

Author(s):

Huihua Li ◽

Yik-Ying Teo ◽

Eng-King Tan

Keyword(s):

Linkage Disequilibrium ◽

Genetic Association ◽

Association Studies ◽

Genetic Association Studies

Download Full-text

Evaluation of genome-wide power of genetic association studies based on empirical data from the HapMap project

Human Molecular Genetics ◽

10.1093/hmg/ddm205 ◽

2007 ◽

Vol 16 (20) ◽

pp. 2494-2505 ◽

Cited By ~ 23

Author(s):

Yasuhito Nannya ◽

Kenjiro Taura ◽

Mineo Kurokawa ◽

Shigeru Chiba ◽

Seishi Ogawa

Keyword(s):

Genetic Association ◽

Empirical Data ◽

Association Studies ◽

Genetic Association Studies ◽

Hapmap Project ◽

Genome Wide

Download Full-text

Clinical, biochemical and genetic risk factors for 30-day and 5-year mortality in 518 adult patients subjected to cardiopulmonary bypass during cardiac surgery - the INFLACOR study.

Acta Biochimica Polonica ◽

10.18388/abp.2017_2361 ◽

2018 ◽

Vol 65 (2) ◽

pp. 241-250 ◽

Cited By ~ 3

Author(s):

Maciej Michał Kowalik ◽

Romuald Lango ◽

Piotr Siondalski ◽

Magdalena Chmara ◽

Maciej Brzeziński ◽

...

Keyword(s):

Risk Factors ◽

Cardiac Surgery ◽

Cardiopulmonary Bypass ◽

Genetic Association ◽

Biochemical Parameters ◽

Cox Regression ◽

Association Studies ◽

Nyha Class ◽

Genetic Association Studies ◽

Chronic Obstructive

There is increasing evidence that genetic variability influence patients’ early morbidity after cardiac surgery performed using cardiopulmonary bypass (CPB). The use of mortality as an outcome measure in cardiac surgical genetic association studies is rare. We publish the 30-day and 5-year survival analyses with focus on pre-, intra-, postoperative variables, biochemical parameters, and genetic variants in the INFLACOR (INFlAmmation in Cardiac OpeRations) cohort.In a series of prospectively recruited 518 adult Polish Caucasians who underwent cardiac surgery in which CPB was used, the clinical data, biochemical parameters, IL-6, soluble ICAM-1, TNFa, soluble E-selectin, and 10 single nucleotide polymorphisms were evaluated for their associations with 30-day and 5-year mortality.The 30-day mortality was associated with: pre-operative prothrombin international normalized ratio, intra-operative blood lactate, postoperative serum creatine phosphokinase, and acute kidney injury requiring renal replacement therapy (AKI-RRT) in logistic regression. Factors that determined the 5-year survival included: pre-operative NYHA class, history of peripheral artery disease and severe chronic obstructive pulmonary disease, intra-operative blood transfusion; and postoperative peripheral hypothermia, myocardial infarction, infection, and AKI-RRT in Cox regression. The serum levels of IL-6 and ICAM-1 measured three hours after operation were associated with 30-day and 5-year mortality, respectively. The ICAM1 rs5498 was associated with 30-day and 5-year survival with borderline significance.Different risk factors determined the early (30-day) and late (5-year) survival after adult cardiac surgery in which cardiopulmonary bypass was used. Future genetic association studies in cardiac surgical patients should adjust for the identified chronic and acute postoperative risk factors.

Download Full-text