Digital Commons Network^™

Unravelling The Genetic Basis Of Schizophrenia, Clara Casey, John F. Fullard, Roy D. Sleator

Department of Biological Sciences Publications

Neuronal development is a highly regulated mechanism that is central to organismal function in animals. In humans, disruptions to this process can lead to a range of neurodevelopmental phenotypes, including Schizophrenia (SCZ). SCZ has a significant genetic component, whereby an individual with an SCZ affected family member is eight times more likely to develop the disease than someone with no family history of SCZ. By examining a combination of genomic, transcriptomic and epigenomic datasets, large-scale ‘omics’ studies aim to delineate the relationship between genetic variation and abnormal cellular activity in the SCZ brain. Herein, we provide a brief overview of …

The Origin And Dispersal Of Austroasiatic Languages From The Perspectives Of Linguistics, Archeology And Genetics, Jian Yu, Xiaohua Deng, Zhiquan Fan, Wenjiao Yang, Zhi Ji, Chuanchao Wang

Human Biology Open Access Pre-Prints

The Austroasiatic (AA) languages are a large language family in Mainland Southeast and South Asia. Theoretical, methodological, and material constraints have limited research on the origin and dispersal of AA-speaking populations within historical-comparative linguistics. With the deepening of archaeological and genetic studies, interdisciplinary collaboration has become the key to solving this problem. Based on the latest achievements of linguistics, archaeology and molecular anthropology, we review the hypotheses and propose insights on the origin and dispersal of AA languages. The ancestors of the AA-speaking populations were suggested to be the rice farmers living in the Neolithic Age in southern China. During …

Biol 440-002: Cell Biology Of Disease, Darshan Desai

Biology Syllabi

No abstract provided.

Biol 628-002: Cell Biology Of Disease, Darshan Desai

Biology Syllabi

No abstract provided.

Soybean Genetics, Genomics, And Breeding For Improving Nutritional Value And Reducing Antinutritional Traits In Food And Feed, William M. Singer, Yi-Chen Lee, Zachary Shea, Caio Canella Vieira, Dongho Lee, Xiaoying Li, Mia Cunicelli, Shaila S. Kadam, Mohammad Amir Waseem Khan, Grover Shannon, M. A. Rouf Mian, Henry T. Nguyen, Bo Zhang

Agriculture Faculty Publications

Soybean [Glycine max(L.) Merr.] is a globally important crop due to its valuable seed composition, versatile feed, food, and industrial end-uses, and consistent genetic gain. Successful genetic gain in soybean has led to widespread adaptation and increased value for producers, processors, and consumers. Specific focus on the nutritional quality of soybean seed composition for food and feed has further elucidated genetic knowledge and bolstered breeding progress. Seed components are historical and current targets for soybean breeders seeking to improve nutritional quality of soybean. This article reviews genetic and genomic foundations for improvement of nutritionally important traits, such as protein and …

Beyond The Basics: Unraveling The Complexity Of Coronary Artery Calcification, Satwat Hashmi, Pashmina Wiqar Shah, Zouhair Aherrahrou, Elena Aikawa, Rédouane Aherrahrou

Department of Biological & Biomedical Sciences

Coronary artery calcification (CAC) is mainly associated with coronary atherosclerosis, which is an indicator of coronary artery disease (CAD). CAC refers to the accumulation of calcium phosphate deposits, classified as micro- or macrocalcifications, that lead to the hardening and narrowing of the coronary arteries. CAC is a strong predictor of future cardiovascular events, such as myocardial infarction and sudden death. Our narrative review focuses on the pathophysiology of CAC, exploring its link to plaque vulnerability, genetic factors, and how race and sex can affect the condition. We also examined the connection between the gut microbiome and CAC, and the impact …

A Phenotypically Robust Model Of Spinal And Bulbar Muscular Atrophy In Drosophila, Kristin Richardson, Medha Sengupta, Alyson Sujkowski, Kozeta Libohova, Autumn C. Harris, Robert Wessells, Diane E. Merry, Sokol V. Todi

Department of Biochemistry and Molecular Biology Faculty Papers

Spinal and bulbar muscular atrophy (SBMA) is an X-linked disorder that affects males who inherit the androgen receptor (AR) gene with an abnormal CAG triplet repeat expansion. The resulting protein contains an elongated polyglutamine (polyQ) tract and causes motor neuron degeneration in an androgen-dependent manner. The precise molecular sequelae of SBMA are unclear. To assist with its investigation and the identification of therapeutic options, we report here a new model of SBMA in Drosophila melanogaster. We generated transgenic flies that express the full-length, human AR with a wild-type or pathogenic polyQ repeat. Each transgene is inserted into the same safe …

Inference Of Admixture Origins In Indigenous African Cattle., Kwondo Kim, Donghee Kim, Olivier Hanotte, Charles Lee, Heebal Kim, Choongwon Jeong

Faculty Research 2023

Present-day African cattle retain a unique genetic profile composed of a mixture of the Bos taurus and Bos indicus populations introduced into the continent at different time periods. However, details of the admixture history and the exact origins of the source populations remain obscure. Here, we infer the source of admixture in the earliest domestic cattle in Africa, African taurine. We detect a significant contribution (up to ∼20%) from a basal taurine lineage, which might represent the now-extinct African aurochs. In addition, we show that the indicine ancestry of African cattle, although most closely related to so-far sampled North Indian …

Dna Barcoding Indicates Multiple Invasions Of The Freshwater Snail Melanoides Tuberculata Sensu Lato In Florida, Lori Tolley-Jordan, Michael A. Chadwick, Jimmy K. Triplett

Research, Publications & Creative Work

Melanoides tuberculata sensu lato (Thiaridae) are polymorphic female-clonal snails of Asian and African origins that have invaded freshwaters worldwide, including those in Florida. Although the snails have been documented in Florida for at least 70 years, no studies have investigated whether the observed distribution is due to a single introduction or multiple independent invasions. Here, cytochrome oxidase I was used to measure genetic diversity within and among sites in Florida and compare genetic diversity between Florida and other regions of the world. We also examined the relationship between shell morphology and haplotype diversity to determine if shell morphs can serve …

Alzheimer’S Disease Genetic Risk And Cognitive Reserve In Relationship To Long-Term Cognitive Trajectories Among Cognitively Normal Individuals, Corinne Pettigrew, Jurijs Nazarovs, Anja Soldan, Vikas Singh, Jiangxia Wang, Timothy Hohman, Logan Dumitrescu, Julia Libby, Brian Kunkle, Alden L. Gross, Sterling Johnson, Qiongshi Lu, Corinne Engelman, Colin L. Masters, Paul Maruff, Simon M. Laws, John C. Morris, Jason Hassenstab, Carlos Cruchaga, Susan M. Resnick, Melissa H. Kitner-Triolo, Yang An, Marilyn Albert

Research outputs 2022 to 2026

Background:

Both Alzheimer’s disease (AD) genetic risk factors and indices of cognitive reserve (CR) influence risk of cognitive decline, but it remains unclear whether they interact. This study examined whether a CR index score modifies the relationship between AD genetic risk factors and long-term cognitive trajectories in a large sample of individuals with normal cognition.

Methods:

Analyses used data from the Preclinical AD Consortium, including harmonized data from 5 longitudinal cohort studies. Participants were cognitively normal at baseline (M baseline age = 64 years, 59% female) and underwent 10 years of follow-up, on average. AD genetic risk was measured by …

Engaging Students In A Genetics Course-Based Undergraduate Research Experience Utilizing Caenorhabditis Elegans In Hybrid Learning To Explore Human Disease Gene Variants, Natalie Forte, Virginia Veasey, Bethany Christie, Amira Carter, Marli Hanks, Alan Holderfield, Taylor Houston, Anil Challa, Ashley Turner

Research, Publications & Creative Work

Genetic analysis in model systems using bioinformatic approaches provides a rich context for a concrete and conceptual understanding of gene structure and function. With the intent to engage students in research and explore disease biology utilizing the nematode Caenorhabditis elegans model, we developed a semester-long course-based undergraduate research experience (CURE) in a hybrid (online/in-person) learning environment—the gene-editing and evolutionary nematode exploration CURE (GENE-CURE). Using a combination of bioinformatic and molecular genetic tools, students performed structure-function analysis of disease-associated variants of uncertain significance (VUS) in human orthologs. With the aid of a series of workshop-style research sessions, students worked in teams …

Multivariate Adaptive Shrinkage Improves Cross-Population Transcriptome Prediction And Association Studies In Underrepresented Populations, Daniel Araujo, Chris Nguyen, Xiaowei Hu, Anna V. Mikhaylova, Christopher R. Gignoux, Kristin Ardlie, Kent D. Taylor, Peter Durda, Yongmei Liu, George Papanicolaou, Michael H. Cho, Stephen S. Rich, Jerome I. Rotter, Nhlbi Topmed Consortium, Hae Kyung Im, Ani Manichaikul, Heather Wheeler

Biology: Faculty Publications and Other Works

Transcriptome prediction models built with data from European-descent individuals are less accurate when applied to different populations because of differences in linkage disequilibrium patterns and allele frequencies. We hypothesized that methods that leverage shared regulatory effects across different conditions, in this case, across different populations, may improve cross-population transcriptome prediction. To test this hypothesis, we made transcriptome prediction models for use in transcriptome-wide association studies (TWASs) using different methods (elastic net, joint-tissue imputation [JTI], matrix expression quantitative trait loci [Matrix eQTL], multivariate adaptive shrinkage in R [MASHR], and transcriptome-integrated genetic association resource [TIGAR]) and tested their out-of-sample transcriptome prediction accuracy …

Mystery Mutt: Dna Analysis With A Dog Named Charlie, Kelly M. Jones

Inclusive Strategies for Teaching Secondary Mathematics and Science

This article provides an in-depth exploration of the design, execution, and outcomes of the "Mystery Mutt: DNA analysis with a dog named Charlie" lesson. Designed for seventh-grade life science students, the lesson focuses on unraveling the correlation between genotype and phenotype using authentic pet DNA test results. Grounded in real-life experiences and employing a multi-dimensional approach, the lesson successfully bridges the gap between theoretical genetic concepts and practical applications. The article discusses the lesson's alignment with academic standards, consideration of materials and safety, its unique classroom context, and the engaging phases of exploration, explanation, elaboration, evaluation, and closure. The emphasis …

Craniofacial Features Of Polr3-Related Leukodystrophy Caused By Biallelic Variants In Polr3a, Polr3b And Polr1c, Amytice Mirchi, Simon-Pierre Guay, Luan T. Tran, Nicole I. Wolf, Adeline Vanderver, Bernard Brais, Michel Sylvain, Daniela Pohl, Elsa Rossignol, Michael Saito, Sebastien Moutton, Luis González-Gutiérrez-Solana, Isabelle Thiffault, Michael C. Kruer, Dolores Gonzales Moron, Marcelo Kauffman, Cyril Goizet, László Sztriha, Emma Glamuzina, Serge B. Melançon, Sakkubai Naidu, Jean-Marc Retrouvey, Suzanne Lacombe, Beatriz Bernardino-Cuesta, Isabelle De Bie, Geneviève Bernard

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: RNA polymerase III-related or 4H leukodystrophy (POLR3-HLD) is an autosomal recessive hypomyelinating leukodystrophy characterized by neurological dysfunction, hypodontia and hypogonadotropic hypogonadism. The disease is caused by biallelic pathogenic variants in POLR3A, POLR3B, POLR1C or POLR3K. Craniofacial abnormalities reminiscent of Treacher Collins syndrome have been originally described in patients with POLR3-HLD caused by biallelic pathogenic variants in POLR1C. To date, no published studies have appraised in detail the craniofacial features of patients with POLR3-HLD. In this work, the specific craniofacial characteristics of patients with POLR3-HLD associated with biallelic pathogenic variants in POLR3A, POLR3B and POLR1C …

Gene-By-Environment Interaction In Non-Alcoholic Fatty Liver Disease And Depression: The Role Of Hepatic Transaminases, Eron G. Manusov, Vincent P. Diego, Edward Abrego, Kathryn Herklotz, Marcio A. Almeida, Xi Mao, Sandra L. Laston, John Blangero, Sarah Williams-Blangero

School of Medicine Publications and Presentations

Non-alcoholic fatty liver disease (NAFLD) encompasses a range of liver conditions, from benign fatty accumulation to severe fibrosis. The global prevalence of NAFLD has risen to 25-30%, with variations across ethnic groups. NAFLD may advance to hepatocellular carcinoma, increases cardiovascular risk, is associated with chronic kidney disease, and is an independent metabolic disease risk factor. Assessment methods for liver health include liver biopsy, magnetic resonance imaging, ultrasound, and vibration-controlled transient elastography (VCTE by FibroScan). Hepatic transaminases are cost-effective and minimally invasive liver health assessment methods options.

This study focuses on the interaction between genetic factors underlying the traits (hepatic transaminases …

Global Serum Profiling: An Opportunity For Earlier Cancer Detection., Alexandra Sala, James M. Cameron, Paul M. Brennan, Emma J. Crosbie, Tom Curran, Ewan Gray, Pierre Martin-Hirsch, David S. Palmer, Ihtesham U. Rehman, Nicholas J W Rattray, Matthew J. Baker

Manuscripts, Articles, Book Chapters and Other Papers

The advances in cancer research achieved in the last 50 years have been remarkable and have provided a deeper knowledge of this disease in many of its conceptual and biochemical aspects. From viewing a tumor as a 'simple' aggregate of mutant cells and focusing on detecting key cell changes leading to the tumorigenesis, the understanding of cancer has broadened to consider it as a complex organ interacting with its close and far surroundings through tumor and non-tumor cells, metabolic mechanisms, and immune processes. Metabolism and the immune system have been linked to tumorigenesis and malignancy progression along with cancer-specific genetic …

Loss Of Pml Nuclear Bodies In Familial Amyotrophic Lateral Sclerosis-Frontotemporal Dementia, Francesco Antoniani, Marco Cimino, Laura Mediani, Jonathan Vinet, Enza M. Verde, Valentina Secco, Alfred Yamoah, Priyanka Tripathi, Eleonora Aronica, Maria Elena Cicardi, Davide Trotti, Jared Sterneckert, Anand Goswami, Serena Carra

Farber Institute for Neuroscience Faculty Papers

Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD) are two neurodegenerative disorders that share genetic causes and pathogenic mechanisms. The critical genetic players of ALS and FTD are the TARDBP, FUS and C9orf72 genes, whose protein products, TDP-43, FUS and the C9orf72-dipeptide repeat proteins, accumulate in form of cytoplasmic inclusions. The majority of the studies focus on the understanding of how cells control TDP-43 and FUS aggregation in the cytoplasm, overlooking how dysfunctions occurring at the nuclear level may influence the maintenance of protein solubility outside of the nucleus. However, protein quality control (PQC) systems that maintain protein homeostasis comprise …

Ms 088 Guide To John L. Decker, Md Papers (1931-1992), John L. Decker (1921-2000)

Manuscript Finding Aids

The papers of John L. Decker, MD primarily document his work at the National Institute of Health (NIH) as well as his involvment in professional organizations. His travel to and participation in conferences, lectures, and professional committees make up a significant portion of the papers. The papers mostly correspond to Decker's stint at the NIH, 1965-1990. However some date as far back as 1931 and as late as 1992. See more at MS 088.

Phenotype And Genetic Analysis Of Data Collected Within The First Year Of Neurodev, Patricia Kipkemoi, Heesu Ally Kim, Bjorn Christ, Emily O’Heir, Jake Allen, Christina Austin-Tse, Samantha Baxter, Amina Abubakar, Charles Newton, Alicia Martin

Institute for Human Development

Genetic association studies have made significant contributions to our understanding of the etiology of neurodevelopmental disorders (NDDs). However, these studies rarely focused on the African continent. The NeuroDev Project aims to address this diversity gap through detailed phenotypic and genetic characterization of children with NDDs from Kenya and South Africa. We present results from NeuroDev’s first year of data collection, including phenotype data from 206 cases and clinical genetic analyses of 99 parent-child trios. Most cases met criteria for global developmental delay/intellectual disability (GDD/ID, 80.3%). Approximately half of the children with GDD/ID also met criteria for autism. Analysis of exome-sequencing …

Apoe4, Age, And Sex Regulate Respiratory Plasticity Elicited By Acute Intermittent Hypercapnic-Hypoxia, Jayakrishnan Nair, Joseph F. Welch, Alexandria B. Marciante, Tingting Hou, Qing Lu, Emily J. Fox, Gordon S. Mitchell

Department of Physical Therapy Faculty Papers

Rational

Acute intermittent hypoxia (AIH) shows promise for enhancing motor recovery in chronic spinal cord injuries and neurodegenerative diseases. However, human trials of AIH have reported significant variability in individual responses.

Objectives

Identify individual factors (eg, genetics, age, and sex) that determine response magnitude of healthy adults to an optimized AIH protocol, acute intermittent hypercapnic-hypoxia (AIHH).

Methods

In 17 healthy individuals (age = 27 ± 5 yr), associations between individual factors and changes in the magnitude of AIHH (15, 1-min O2 = 9.5%, CO2 = 5% episodes) induced changes in diaphragm motor-evoked potential (MEP) amplitude and inspiratory mouth occlusion pressures …

Irf7 And Unc93b1 Variants In An Infant With Recurrent Herpes Simplex Virus Infection., Megan H. Tucker, Wei Yu, Heather Menden, Sheng Xia, Carl F. Schreck, Margaret Gibson, Daniel A. Louiselle, T Pastinen, Nikita Raje, Venkatesh Sampath

Manuscripts, Articles, Book Chapters and Other Papers

Neonatal herpes simplex virus (HSV) infection is a devastating disease with substantial morbidity and mortality. The genetic basis of susceptibility to HSV in neonates remains undefined. We evaluated a male infant with neonatal skin/eye/mouth (SEM) HSV-1 disease, who had complete recovery after acyclovir but developed HSV-1 encephalitis at 1 year of age. An immune workup showed an anergic PBMC cytokine response to TLR3 stimulation but no other TLRs. Exome sequencing identified rare missense variants in IFN-regulatory factor 7 (IRF7) and UNC-93 homolog B1 (UNC93B1). PBMC single-cell RNA-Seq done during childhood revealed decreased expression of several innate immune genes and a …

Mechanobiology As A Tool For Addressing The Genotype-To- Phenotype Problem In Microbiology, Merrill E. Asp, Minh-Tri Ho Thanh, Subarna Dutta, Jessica A. Comstock, Roy D. Welch, Alison E. Patteson

Physics - All Scholarship

The central hypothesis of the genotype–phenotype relationship is that the phenotype of a developing organism (i.e., its set of observable attributes) depends on its genome and the environment. However, as we learn more about the genetics and biochemistry of living systems, our understanding does not fully extend to the complex multiscale nature of how cells move, interact, and organize; this gap in understanding is referred to as the genotype-to-phenotype problem. The physics of soft matter sets the background on which living organisms evolved, and the cell environment is a strong determinant of cell phenotype. This inevitably leads to challenges as …

Understanding The Relationship Between B Chromosomes And Nondisjunction In Drosophila Melanogaster, Ayushi Patel

Honors Scholar Theses

B chromosomes are supernumerary, heterochromatic genetic elements that are found in hundreds of different plant and animal species. Recently, B chromosomes were discovered in a stock of Drosophila melanogaster and are carried at a high copy number of 10-12 B chromosomes per cell. B chromosomes are not known to carry any active genes, but when placed in a wild-type genetic background, they cause a significant increase in the frequency of chromosome 4 missegregation during meiosis. This project aimed to understand the relationship between a female’s B chromosome copy number and how often she passes on too many (or too few) …

The Presence Of Childhood Obesity In Nebraska And The Physiological Repercussions Of The Disease, Madison R. Bezousek

Honors Theses

Childhood Obesity can cause lifelong repercussions in children and adults. There has been stigma around the causes of obesity and its relation to lifestyle choices, without consideration of the genetic and syndromic causes. In this literature review the causes of obesity were investigated, along with the effect on the physiological systems and the enviornmental factors that are continuing the obesity epidemic. Preventing and treating lifestyle obesity is something that is seen to have the greatest effect on youth, especially with intergenerational obesity. Nebraska schools have implemented programs to encourage healthy living, and ongoing research is being implemented to reduce the …

Preweaning Performance In F1 Katahdin X East Friesian Crossbred Lambs, Homero Salinas, Eric Grosse, Troy Wieberg, Jorge Maldonado-Jaquez, Glafiro Torres

Title III Professional Development Reports

Previous studies at Lincoln University indicated that the Katahdin sheep could perform well on pasture in a warm and humid climate and tolerate GIP. However, the preweaning performance of the crossbreed of Katahdin (Kt) and East Friesian (EF) in Missouri still needs to be characterized. So, this preliminary study aimed to evaluate the preweaning performance of lambs (1/2EF x 1/2Kt) from Katahdin ewes crossbred with East Friesian Ram. Forty-three lambs born in Spring 2022 from 27 of second lambing Katahdin ewes and one-year East Friesian ram were weighted and tagged at birth, after five days of colostrum, were weighed every …

Focal Adhesion Is Associated With Lithium Response In Bipolar Disorder: Evidence From A Network-Based Multi-Omics Analysis, Vipavee Niemsiri, Sara Brin Rosenthal, Caroline M. Nievergelt, Adam X. Maihofer, Maria C. Marchetto, Renata Santos, Tatyana Shekhtman, Ney Alliey-Rodriguez, Amit Anand, Yokesh Balaraman

School of Medicine Publications and Presentations

Lithium (Li) is one of the most effective drugs for treating bipolar disorder (BD), however, there is presently no way to predict response to guide treatment. The aim of this study is to identify functional genes and pathways that distinguish BD Li responders (LR) from BD Li non-responders (NR). An initial Pharmacogenomics of Bipolar Disorder study (PGBD) GWAS of lithium response did not provide any significant results. As a result, we then employed network-based integrative analysis of transcriptomic and genomic data. In transcriptomic study of iPSC-derived neurons, 41 significantly differentially expressed (DE) genes were identified in LR vs NR regardless …

Protocol To Identify The Core Gene Supported By An Essential Gene In E. Coli Bacteria Using A Genome-Wide Suppressor Screen, Isao Masuda, Ya-Ming Hou

Department of Biochemistry and Molecular Biology Faculty Papers

We describe here a genome-wide screening approach to identify the most critical core reaction among a network of many that are supported by an essential gene to establish cell viability. We describe steps for maintenance plasmid construction, knockout cell construction, and phenotype validation. We then detail isolation of suppressors, whole-genome sequencing analysis, and reconstruction of CRISPR mutants. We focus on E. coli trmD, which encodes an essential methyl transferase that synthesizes m1G37 on the 3'-side of the tRNA anticodon. For complete details on the use and execution of this protocol, please refer to Masuda et al. (2022).

Cocktail-Party Listening And Cognitive Abilities Show Strong Pleiotropy, Samuel R. Mathias, Emma M. Knowles, Josephine Mollon, Peter T. Fox, Rene L. Olvera, Juan M. Peralta, Satish Kumar, Harald H. H. Goring, Ravi Duggirala, Joanne E. Curran, John Blangero, David C. Glahn

School of Medicine Publications and Presentations

Introduction: The cocktail-party problem refers to the difficulty listeners face when trying to attend to relevant sounds that are mixed with irrelevant ones. Previous studies have shown that solving these problems relies on perceptual as well as cognitive processes. Previously, we showed that speech-reception thresholds (SRTs) on a cocktail-party listening task were influenced by genetic factors. Here, we estimated the degree to which these genetic factors overlapped with those influencing cognitive abilities.

Methods: We measured SRTs and hearing thresholds (HTs) in 493 listeners, who ranged in age from 18 to 91 years old. The same individuals completed a cognitive test …

Potential Mirna Biomarkers And Therapeutic Targets For Early Atherosclerotic Lesions, Genesio M. Karere, Jeremy P. Glenn, Ge Li, Ayati Konar, John L. Vandeberg, Laura A. Cox

School of Medicine Publications and Presentations

Identification of potential therapeutic targets and biomarkers indicative of burden of early atherosclerosis that occur prior to advancement to life-threatening unstable plaques is the key to eradication of CAD prevalence and incidences. We challenged 16 baboons with a high cholesterol, high fat diet for 2 years and evaluated early-stage atherosclerotic lesions (fatty streaks, FS, and fibrous plaques, FP) in formalin-fixed common iliac arteries (CIA). We used small RNA sequencing to identify expressed miRNAs in CIA and in baseline blood samples of the same animals. We found 412 expressed miRNAs in CIA and 356 in blood samples. Eight miRNAs (miR-7975, -486-5p, …

Uncovering The Complex Genetic Architecture Of Human Plasma Lipidome Using Machine Learning Methods, Miikael Lehtimäki, Binisha H. Mishra, Coral Del-Val, Leo-Pekka Lyytikäinen, Mika Kähönen, C. Robert Cloninger, Olli T. Raitakari, Reijo Laaksonen, Igor Zwir, Terho Lehtimäki, Pashupati P. Mishra

School of Medicine Publications and Presentations

Genetic architecture of plasma lipidome provides insights into regulation of lipid metabolism and related diseases. We applied an unsupervised machine learning method, PGMRA, to discover phenotype-genotype many-to-many relations between genotype and plasma lipidome (phenotype) in order to identify the genetic architecture of plasma lipidome profiled from 1,426 Finnish individuals aged 30–45 years. PGMRA involves biclustering genotype and lipidome data independently followed by their inter-domain integration based on hypergeometric tests of the number of shared individuals. Pathway enrichment analysis was performed on the SNP sets to identify their associated biological processes. We identified 93 statistically significant (hypergeometric p-value < 0.01) lipidome-genotype relations. Genotype biclusters in these 93 relations contained 5977 SNPs across 3164 genes. Twenty nine of the 93 relations contained genotype biclusters with more than 50% unique SNPs and participants, thus representing most distinct subgroups. We identified 30 significantly enriched biological processes among the SNPs involved in 21 of these 29 most distinct genotype-lipidome subgroups through which the identified genetic variants can influence and regulate plasma lipid related metabolism and profiles. This study identified 29 distinct genotype-lipidome subgroups in the studied Finnish population that may have distinct disease trajectories and therefore could be useful in precision medicine research.