Genetics and Genomics Commons^™

Editorial, Anne M. Friel, Brigid Hooban, Therese Montgomery, Anne Marie O'Brien, Cormac Quigley, Edel Mcneela, Eva Campion, James Walshe, Sinead Loughran

SURE Journal: Science Undergraduate Research Experience Journal

No abstract provided.

Thalamocortical Structural Covariation Networks Are Related To Familial Risk For Schizophrenia In The Context Of Lower Nuclei Volume Estimates In Patients: An Enigma Study, Annalisa Lella, Linda A. Antonucci, Roberta Passiatore, Loredana Bellantuono, Pierluigi Selvaggi, Teresa Popolizio, Guido Di Sciascio, Alessandro Saponaro, Patrizia Ricci, John Blangero

School of Medicine Publications

Background

Structural brain differences in the thalamus and the cortex have been widely reported in schizophrenia (SCZ) relative to neurotypical control individuals (NCs). Most previous studies examined the thalamusas a whole as a single region of interest. In addition, findings in individuals at familial high risk for SCZ (FHRs) remain inconclusive. Here, we investigated whether local and network-wide thalamic-related structural alterations vary as a function of familial risk for SCZ.

Methods

Structural magnetic resonance imaging scans were obtained from 5197 participants (NC, n = 3409; FHR, n = 257; SCZ, n = 1531) across 32 cross-sectional samples within the …

Bioaccumulation Pattern Of Per- And Polyfluoroalkyl Substances (Pfas) In Fish Tissues From Two Freshwater Systems, Margaret D. Taiwo, Husam Kafeenah, David D. Duvernell, Michael O. Eze

Biological Sciences Faculty Research & Creative Works

Per- and polyfluoroalkyl substances (PFAS) are known for their persistence, ubiquity, bioaccumulation in different matrices of the environment and their detrimental effect on human health. In this study, we used EPA 1633 to examine the prevalence of ten PFAS compounds in two freshwater systems and investigated their bioaccumulation pattern across different tissues of grass carp fish (Ctenopharyngodon idella), common carp (Cyprinus carpio), and flathead catfish (Pylodictis olivaris). Among the PFAS compounds analyzed, PFBS exhibited the highest concentration in the freshwater sample, exceeding the U.S. EPA regulatory limit of 4 ng/L for drinking water. The total PFAS concentrations in the muscle, …

Dusky Grouse Seasonal Resource Selection In The Great Basin Isolated Mountain Ranges Of Nevada, Usa, Stephanie Landry, Brian Smith, Erica Stuber, Shawn Espinosa, David Dahlgren

Aspen Bibliography

Dusky grouse Dendragapus obscurus are a montane forest grouse species with a paucity of information regarding their temporal and spatial resource use during critical times of high mortality and reproductive output. This lack of vital data may leave dusky grouse at risk of sub-optimal management in many areas of their distribution, especially in the isolated ‘sky island’ mountain ranges of the Great Basin, where high elevation habitats are surrounded by sagebrush and salt desert shrub land flats. Many of these high elevation habitats are being altered and lost rapidly from increasing disturbance events and effects of climate change. Our objective …

Using Rattlesnake Venom To Model Complex Trait Evolution Across Ecological And Evolutionary Scales, Samuel R. Hirst

USF Tampa Graduate Theses and Dissertations

A central challenge in evolutionary biology is understanding how genetic variation leads to phenotypicdiversity, particularly for complex traits that strongly influence fitness. Traits form the substrate of natural selection, but it is genes, that are inherited across generations. To fully understand the evolutionary process, we must therefore connect the molecular basis of trait variation with the evolutionary outcomes of such traits.

For relatively simple traits, the genotype–phenotype relationship is well understood. Classic systems, such as coat color in beach mice or toxin resistance in garter snakes, have provided effective examples of how relatively few loci underlie conspicuous adaptive differences across …

Genetic Characterization And High-Resolution Total Mrna Sequencing Of The Millipede Cherokia Georgiana Bollman, 1889, Elena Cruz

Biology Theses

There are approximately 12,000 described species within the class Diplopoda. Only six species, falling within four of sixteen orders, have fully sequenced genomes. No whole genomes are available for incredibly diverse families like Xystodesmidae. Many interesting characteristics in this group are poorly defined at the genetic level, such as the production of a defensive hydrogen cyanide secretion and UV fluorescence in the order Polydesmida. Here, we present a genetic characterization of the polydesmid millipede Cherokia georgiana Bollman, 1889. We include tissue-specific sequencing metrics, alignment and assembly of mitochondrial DNA consensus sequence according to tissue type, and phylogenetic tree construction using …

Purple Tomatoes Boost Nutrition Crop Value And Create New Opportunities For United States (U.S) Agriculture, Tariq Alam

Agronomic Crops

The agricultural landscape in the United States is continually evolving, with growers and the tomato industry seeking innovative ways to meet consumer demands while enhancing profitability. The introduction of both bioengineered and classically bred anthocyanins-enriched purple tomatoes presents a unique opportunity for U.S. growers to cultivate a high-value crop that appeals to niche markets and commands premium pricing. Bioengineered purple tomatoes achieve high anthocyanin levels through the introduction of snapdragon transcription factors, while classically bred 'Indigo Rose' purple tomatoes are developed via classical breeding methods, providing an alternative for consumers who prefer traditionally bred products. Specifically, the purple tomato holds …

Understanding Callus Types In Maize By Genetic Mapping And Transcriptional Profiling, Guifang Lin, Yan Liu, Tej Man Tamang, Yang Qin, Mingxia Zhao, Hairong Wei, Et. Al.

Michigan Tech Publications

Plant transformation efficiency is highly dependent on species, individual genotypes, and tissue types. In maize, immature embryos are regularly used for transformation. The process relies heavily on callus development, as it is intricately associated with somatic embryogenesis and subsequent plant regeneration, both of which directly affect transformation efficiency. Immature embryos of the segregation progeny derived from the two inbred parents, a transformation-amenable line A188 and a recalcitrant line B73, can be cultured to form two primary callus types: Type I and Type II. The Type II callus grows faster and is a favorable type for regeneration. Here, Type I and …

Flawed Analysis Invalidates Claim Of A Strong Yellowstone Trophic Cascade After Wolf Reintroduction: A Comment On Ripple Et Al. (2025), Dan R. Macnulty, David Cooper, Michael Procko, T.J. Clark-Wolf

Aspen Bibliography

Ripple et al. (2025) recently argued that large carnivore recovery in Yellowstone National Park triggered one of the world’s strongest trophic cascades, citing a ∼1500 % increase in willow crown volume derived from plant height data. In this comment, we show that their conclusion is invalid due to fundamental methodological flaws. These include use of a tautological volume model, violations of key modeling assumptions, comparisons across unmatched plots, and the misapplication of equilibrium-based metrics in a non-equilibrium system. Additionally, Ripple et al. rely on selectively framed photographic evidence and omit critical drivers such as human hunting in their causal attribution. …

Organism-Specific Sequence Motifs Link Ribosomal Rnas To Brain Disorders, Isidore Rigoutsos, Stepan Nersisyan, Eric Londin, Iliza Nazeraj, Bonnie Dong, Anastasios Vourekas, Phillipe Loher

Computational Medicine Center Faculty Papers

We report that in humans, mice, fruit flies, and worms, the ribosomal RNAs and the transcribed spacers of 45S are densely packed with organism-specific sequence motifs that are primarily shared with nervous system genes. The human ribosomal RNAs and 45S spacers contain 1,723 such motifs. Specific combinations of these motifs are predominantly found in 3,430 human nervous system genes, of which 1,046 are genes associated with brain disorders, including autism spectrum disorder and schizophrenia. The sequences of the 1,723 motifs and their locations in the introns and exons of nervous system genes are unique to primates. Experimental evidence indicates that …

Decoding Genetic And Network Signatures Of Susceptibility To Orthodontic Root Resorption: Toward Predictive And Personalized Orthodontics, Casey Morishige, Morgan Mecham, Gabriel Eisenhuth, Shilpa Bhandi, Frank Licari, Shankargouda Patil

Annual Research Symposium

No abstract provided.

Evaluating The Potential And Limitations Of Nanopore Adaptive Sampling For Targeted Transcriptome Sequencing, Nicole Debruyne, Feng Wang, Yang Xu, Lan Lin

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Long-read RNA sequencing is a powerful technology for transcriptomics, but low throughput and high cost pose challenges. Adaptive sampling, a feature of Oxford Nanopore Technologies, offers real-time enrichment by selectively ejecting non-target molecules. We evaluate adaptive sampling for human transcriptome analysis. Adaptive sampling modestly enriches target transcripts (1.3 × for cDNA sequencing, 1.9 × for direct RNA sequencing) while preserving gene expression and splicing profiles, but is significantly less effective than cDNA hybridization capture. Short read lengths and low sequencing quality limit performance. Adaptive sampling on direct RNA sequencing can boost target yield (~ 20%) within fixed run times, potentially …

Search, The Jackson Laboratory

Search Magazine

No abstract provided.

Mhc Gene Analysis And Immune Variation In Lepidodactylus Lugubris (The Mourning Gecko), Helen T. Vu

2025 Fall Honors Capstones Projects - Archive

The major histocompatibility complex (MHC) plays a central role in vertebrate immune defense by enabling pathogen recognition and initiating adaptive immune responses. While MHC diversity has been extensively studied in sexually reproducing species, comparatively little is known about its evolution in asexual lineages. The parthenogenetic gecko Lepidodactylus lugubris provides a unique opportunity to investigate how clonality and hybrid origins influence immune gene diversity. By leveraging whole-genome data, this study overcomes the limitations of previous transcriptome-based analyses and provides a more comprehensive view of MHC diversity in a clonal vertebrate. As the first step towards understanding MHC evolution in parthenogenetic lizards, …

Bioinformatic Analysis Of Pogz Variants In Relation To White Sutton Syndrome, Hannah Rollins

Theses

White-Sutton syndrome (WHSUS) is a rare neurodevelopmental disorder caused by mutations in the Pogo Transposable Element with ZNF Domain (POGZ) gene, which encodes pogo-transposable element with ZNF domain, a chromatin regulator essential for proper mitotic progression and DNA repair. This study uses a bioinformatic framework to evaluate the structural and functional impact of missense mutations in the conserved amino acid region (positions 500–800) of the POGZ protein. Protein modeling, variant effect prediction, conservation analysis, and molecular dynamics simulations were employed to gain an understanding of the effects of POGZ missense mutations on protein structure and movement with specific emphasis on …

Genetic Entropy: A Critical Examination, Sarah Hunter

Science, Faith, and Origins

Genetic entropy is a hypothesis proposing that genomes deteriorate over time due to the gradual accumulation of slightly harmful mutations that natural selection cannot effectively remove. This paper explores the scientific debate surrounding this claim by examining differing perspectives on the theory of genetic entropy. Proponents of genetic entropy, such as John Sanford, argue that most mutations are deleterious and fall within a “near-neutral” range, allowing them to accumulate since their effects are too small for natural selection to detect. Evidence to support this claim includes Robert Carter and John Sanford’s research on the deterioration of the H1N1 viral genome …

Investigating The Presence Of R-Loops At The Centromeres Of Drosophila Melanogaster, Daniel D'Souza

Holster Scholar Projects

This study investigates the presence and localization of R-loops at the centromeres of Drosophila melanogaster. R-loops are non-canonical nucleic acid structures that have been implicated in various cellular processes, including genomic instability and accurate chromosome segregation. Although previous research has found R-loops at Drosophila satellite sequences and LTR retrotransposons, their presence and function at the centromeres of a whole organism remain largely unknown. Using IF-FISH (immunofluorescence-fluorescence in situ hybridization), we stained R-loops with the S9.6 antibody. A UAS-rnh1 overexpression line was used to induce the overexpression of RNase H1, an enzyme that resolves R-loops, to confirm the specificity of …

Integrating Multimodal Neuroimaging Of Error Monitoring To Estimate Future Anxiety In Adolescents, Emilio A. Valadez, Stefania Conte, John E. Richards, Yi Feng, Lucrezia Liuzzi, Marco Mcsweeney, Enda Tan, George A. Buzzell, Anderson M. Winkler, Daniel Samuel Pine

Human Genetics Publications

Importance Anxiety disorders are highly prevalent and associated with heightened error monitoring, the detection of one’s mistakes. However, error monitoring, anxiety, and their associations change throughout adolescence, limiting the ability to estimate future anxiety trajectories during this period.

Objective To ascertain whether measures of error monitoring obtained via the integration of electroencephalogram (EEG) and functional magnetic resonance imaging (fMRI) improve estimations of future anxiety compared with EEG or fMRI alone, in adolescents with or without a history of behaviorally inhibited temperament.

Design, Setting, and Participants This longitudinal cohort study was conducted at a university research laboratory and government research hospital. …

Penetrance Of Neurodevelopmental Copy Number Variants Is Associated With Variations In Cortical Morphology, Ana I. Silva, Ida E. Sønderby, George Kirov, Abdel Abdellaoui, Ingrid Agartz, David Ames, Nicola J. Armstrong, Eric Artiges, Tobias Banaschewski, John Blangero

Human Genetics Publications

Background: Copy number variants (CNVs) may increase the risk for neurodevelopmental conditions. The neurobiological mechanisms that link these high-risk genetic variants to clinical phenotypes are largely unknown. An important question is whether brain abnormalities in individuals who carry CNVs are associated with their degree of penetrance.

Methods: We investigated whether increased CNV penetrance for schizophrenia and other developmental disorders was associated with variations in cortical and subcortical morphology. We pooled T1-weighted brain magnetic resonance imaging and genetic data from 22 cohorts from the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis)-CNV consortium. In the main analyses, we included 9268 individuals …

Dynamic Rewiring Of Microrna Networks In The Brainstem Autonomic Control Circuits During Hypertension Development In The Female Spontaneously Hypertensive Rat, Alison Moss, Ankita Srivastava, Lakshmi Kuttippurathu, James S. Schwaber, Rajanikanth Vadigepalli

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

We describe global microRNA (miRNA) changes in the central autonomic control circuits during the development of neurogenic hypertension. Using the female spontaneously hypertensive rat (SHR) and the normotensive Wistar Kyoto (WKY), we analyzed the dynamic miRNA expression changes in three brainstem regions-the nucleus of the solitary tract, caudal ventrolateral medulla, and rostral ventrolateral medulla-as a time series beginning at 8 wk of age before hypertension onset through to extended chronic hypertension. Our analysis yielded nine miRNAs that were significantly differentially regulated in all three regions between SHR and WKY over time. We collated computationally predicted gene targets of these nine …

Picalm Alzheimer’S Risk Allele Causes Aberrant Lipid Droplets In Microglia, Alena Kozlova, Siwei Zhang, Ari Sudwarts, Hanwen Zhang, Stanislau Smirnou, Seul Kee Byeon, Christina Thapa, Xiaotong Sun, Kimberley Stephenson, Xiaojie Zhao, Brendan Jamison, Moorthi Ponnusamy, Xin He, Julie A Schneider, Akhilesh Pandey, David A Bennett, Zhiping P Pang, Alan R Sanders, Hugo J Bellen, Gopal Thinakaran, Jubao Duan

Faculty, Staff and Students Publications

Despite genome-wide association studies (GWAS) of late-onset Alzheimer’s disease (LOAD) having identified many genetic risk loci1–3, the underlying disease mechanisms remain largely unclear. Determining causal disease variants and their LOAD-relevant cellular phenotypes has been a challenge. Here, using our approach for identifying functional GWAS risk variants showing allele-specific open chromatin, we systematically identified putative causal LOAD-risk variants in human induced pluripotent stem (iPS)-cell-derived neurons, astrocytes and microglia, and linked a PICALM LOAD-risk allele to a microglial-specific role of PICALM in lipid droplet (LD) accumulation. Allele-specific open-chromatin mapping revealed functional risk variants for 26 LOAD-risk loci, mostly …

Clinical And Genetic Studies Of Hypotrichosis In District Pakpattan, Punjab, Pakistan, Amir Anees, Muhammad Abdullah, Khawar Hayyat, Muhammad Irshad, Muhammad Iqbal Usama, Muhammad Saleem Khan, Muhammad Rizwan, Muhammad Wajid

Journal of Bioresource Management

Hypotrichosis is a hereditary hair development condition that results in thin or little hair on the head and other regions of the body due to diminished or non-existent hair growth. To investigate the prevalence rate, the mechanism of inheritance, and the genetic counselling of people affected by these conditions. To determine the number of cases of familial hypotrichosis, a survey was done at various schools, colleges, hospitals, and communities to identify those affected by this ailment. A study of eleven families with consanguineous marriages found that 10.52 % of the population had hypotrichosis. The affected individuals had limited hair growth …

Uncovering The Pml::Rara Fusion In Cytogenetically Cryptic And Fish-Negative Acute Promyelocytic Leukemia-A Case Report And Comprehensive Literature Review, Busra Delikkaya, Jaime Eberle-Singh, Arianna Morton, Jerald Gong, Jinglan Liu

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The PML::RARA fusion resulting from t(15;17) is the genetic hallmark of acute promyelocytic leukemia (APL), typically detected by cytogenetics and/or fluorescence in situ hybridization (FISH) studies. Rarely, APL patients present with normal cytogenetics and FISH findings, complicating diagnosis and delaying life-saving therapy. We report a 23-year-old male with clinical, morphologic and immunophenotypic features consistent with APL but negative for FISH studies. Despite prompt initiation of all-trans retinoic acid (ATRA) based on clinical suspicion, the patient succumbed to intracranial hemorrhage. Quantitative reverse transcriptase PCR (qRT-PCR) confirmed a long isoform PML::RARA fusion. A review of 34 published cytogenetics- and FISH-negative cases since …

The Evaluation Of Variants Within Eight Collagen Genes Col1a1, Col1a2, Col3a1, Col5a1, Col11a1, Col15a1, Col22a1, And Col27a1 And A Risk Of Non-Contact Knee Ligament Rupture In Elite Handball Players: A Case-Control Study, Katarzyna Krawczak-Wójcik, Andrzej Mastalerz, Aleksandra Bojarczuk, Monika Johne, Alison V. September, Aleksandra Garbacz, Katarzyna Komar, Ewelina Maculewicz

Baltic Journal of Health and Physical Activity

Introduction: Knee ligament ruptures are common injuries among athletes. While most previous studies examined single collagen gene polymorphisms, few have investigated haplotype-level associations across multiple genes, particularly in elite handball players. Materials and methods: This case-control study analyzed variants in eight collagen genes (COL1A1, COL1A2, COL3A1, COL5A1, COL11A1, COL15A1, COL22A1, and COL27A1) in 103 elite Polish handball players with non-contact knee ligament rupture and 226 matched controls. Results: The COL22A1 rs11784270 CC genotype was associated with an increased risk (OR = 2.88, p = 0.01), with the strongest effect in the …

Early-Life Exposure To Organic Chemical Pollutants As Assessed In Primary Teeth And Cardiometabolic Risk In Mexican American Children: A Pilot Study, Vidya S. Farook, Feroz Akhtar, Rector Arya, Alice Yau, Srinivas Mummidi, Juan Lopez Alvarenga, Alvaro Diaz-Badillo, Roy G. Resendez, John Blangero

Human Genetics Publications

Early-life exposure to organic chemicals (OCs) may influence childhood obesity and associated cardiometabolic risk. These conditions have been shown to disproportionately affect minority populations such as Mexican Americans (MAs). However, information on the impact of organic chemicals on cardiometabolic risk in MA children is limited. Therefore, we conducted a pilot study to assess the extent to which exposure to organic chemicals influences cardiometabolic traits (CMTs) in MA children. We recalled 25 children from a previous study and collected 25 primary teeth from them. Chemical analyses of the teeth were performed using established protocols. Target analytes included acetaminophen (APAP); 3,5,6-trichloro-2-pyridinol (TCPy), …

Teaching Molecular Genetics Using Paramecium And Rna Interference: Research-Based Learning And Project Ownership, M. S. Valentine, K. Johnson, M. B. Veramendi, C. James, J. Kozak, A. Patwardhan, R. Quartey

Montclair State University Scholarship & Creative Works

Research-based course design is beneficial to both the instructor and the students by providing project ownership, independence, increased engagement, and publishable results. Paramecium, a single-celled eukaryote, is a common organism observed in many high school and college classrooms that can be easily cultured and manipulated to navigate through guided student-driven research projects. Presented here are research-centered student projects that include designing and creating an RNA interference (RNAi) plasmid to deplete a gene product in Paramecium. Because RNAi can be used in a large number of model organisms, the techniques presented can be applied in a variety of ways. …

Sequence And Phylogenetic Analysis Of Citrus Maxima (Burm.) Merr. From Tomini Bay, Sulawesi Island, Based On The Maturase K Gene, Brenda Febrina Zusriadi, Novri Youla Kandowangko, Febriyanti Febriyanti

Makara Journal of Science

This study was conducted in the coastal area of Tomini Bay, Sulawesi Island, and it focused on Citrus maxima, a plant known for its unique fruit flesh colors, which range from yellow to pink, and its varying leaf stalk wings. The study aimed to analyze the variations in maturase K (matK) sequences, molecular characteristics, and phylogenetic relationships of two C. maxima samples from Tomini Bay compared to other C. maxima and Citrus species using data available in GenBank. The study utilized DNA barcoding with matK molecular markers, followed by phylogenetic tree construction using the maximum likelihood method …

Detection Method For Escherichia Coli Using Real-Time Polymerase Chain Reaction Targeting The Yhav Gene, Muktiningsih Nurjayadi, Anisa Fitriyanti, Royna Rahma Musie, Gusti Angieta Putri, Puan Aqila Azizah, Helzi Angelina, Grace Grace, Ananda Indah Putri Sihombing, Agus Setiawan, Jefferson Lynford Declan, Gladys Indira Putri, Dandy Akbar Juliansyah, Siti Fatimah, Ayu Berkahingrum, Irma Ratna Kartika, Fera Kurniadewi, Vira Saamia, Shyi-Tien Chen, Bassam Aboemolak, Hesham Ali El Enshasy

Makara Journal of Science

Escherichia coli is a foodborne pathogenic bacterium that can cause diarrhea, while yhaV is a virulence-associated gene linked to the toxin–antitoxin system in E. coli. This study was aimed at evaluating the confirmation, specificity, and sensitivity of a yhaV gene primer using real-time polymerase chain reaction. The yhaV-targeting PCR successfully amplified a DNA fragment with an amplicon length of 207 bp (base pairs) under an annealing temperature optimized to a range of 54 °C to 62 °C via gradient PCR. The PCR using the primer pair produced a consistent Ct (cycle threshold) of 14.14 ± 0.05 and showed …

Where The Buffalo Roam: Ungulate Influences On Quaking Aspen And Willow Communities In The Greater Yellowstone Ecosystem, J. Boone Kauffman, Dian L. Cummings, Robert L. Beschta, William J. Ripple

Aspen Bibliography

Quaking aspen (Populus tremuloides) and willows (Salix spp.) are keystone species of montane and shrub-steppe landscapes of the Western United States. Intact communities dominated by these species provide a wide range of ecosystem services, harboring an exceptional proportion of landscape biodiversity. Land use, especially overgrazing by large ungulates, is among the greatest threats to these ecosystems. To examine the effects of wild ungulates and levels of grazing at Yellowstone National Park (YNP) and the adjacent Gallatin National Forest, we sampled plant community composition and vegetation structure of aspen and willow communities both inside and outside of exclosures. …

Association Of Genetic Scores Related To Insulin Resistance With Neurological Outcomes In Ancestrally Diverse Cohorts From The Trans-Omics For Precision Medicine (Topmed) Program, Chloé Sarnowski, Yixin Zhang, Farah Ammous, Lincoln M. P. Shade, Daniel Dicorpo, Xueqiu Jian, Donna K. Arnett, Thomas R. Austin, John Blangero, Joanne E. Curran

School of Medicine Publications

To better characterize the potential biological mechanisms underlying insulin resistance (IR) and dementia, we derive cross-population and population specific polygenic scores [PSs] for fasting insulin and IR-related partitioned PSs [pPSs]. We conduct a cross-sectional study of the associations of these genetic scores with neurological outcomes in >17k participants (36% men, mean age 55 yrs) from the Trans-Omics for Precision Medicine (TOPMed) program (50% Non-Hispanic White, 23% Black/African American, 21% Hispanic/Latino American, and 4% Asian American). We report significant negative associations (P <  0.002) of the cross-population (P = 1.3 × 10-5) and European (PEA = 3.0 × 10-8) fasting insulin PSs with total cranial volume, and of a metabolic syndrome European PS with general cognitive function (BEA = -0.13, PEA = 0.0002) and lateral ventricular volume (BEA = 0.09, PEA = 0.002). We identify suggestive negative associations (P <  0.007) of metabolic syndrome and obesity pPSs with general cognitive function, and of lipodystrophy pPSs with total cranial volume. A higher genetic predisposition to IR is associated with lower brain size, and a genetic predisposition to specific IR-related type 2 diabetes subtypes, such as metabolic syndrome and mechanisms of IR mediated through obesity and lipodystrophy, is potentially involved in cognitive decline.