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Serum Phosphatidylinositol As A Biomarker For Bipolar Disorder Liability, Emma E. M. Knowles, Peter J. Meikle, Kevin Huynh, Harald H. H. Goring, Rene L. Olvera, Samuel R. Mathias, Ravi Duggirala, Laura Almasy, John Blangero, Joanne E. Curran, David C. Glahn

School of Medicine Publications and Presentations

Objectives

Individuals with bipolar disorder (BPD) exhibit alterations in their phospholipid levels. It is unclear whether these alterations are a secondary consequence of illness state, or if phospholipids and illness risk overlap genetically. If the latter were true, then phospholipids might provide key insights into the pathophysiology of the illness. Therefore, we rank-ordered phospholipid classes by their genetic overlap with BPD risk in order to establish which class might be most informative in terms of increasing our understanding of illness pathophysiology.

Methods

Analyses were conducted in a sample of 558 individuals, unselected for BPD, from 38 extended pedigrees (average family …

The Genetic Basis Of The Comorbidity Between Cannabis Use And Major Depression, Karen Hodgson, Laura Almasy, Emma E. M. Knowles, Jack W. Kent Jr., Joanne E. Curran, Thomas D. Dyer, Harald H. H. Goring, Rene L. Olvera, Mary D. Woolsey, Ravindranath Duggirala, Peter T. Fox, John Blangero, David C. Glahn

School of Medicine Publications and Presentations

Background and aims—While the prevalence of major depression is elevated amongst cannabis users, the role of genetics in this pattern of comorbidity is not clear. This study aimed to estimate the heritability of cannabis use and major depression, quantify the genetic overlap between these two traits, and localize regions of the genome that segregate in families with cannabis use and major depression.

Design—Family-based univariate and bivariate genetic analysis.

Setting—San Antonio, Texas, USA

Participants—Genetics of Brain Structure and Function study (GOBS) participants: 1,284 Mexican-Americans from 75 large multi-generation families and an additional 57 genetically unrelated spouses.

Measurements …

The Arg59trp Variant In Angptl8 (Betatrophin) Is Associated With Total And Hdl-Cholesterol In American Indians And Mexican Americans And Differentially Affects Cleavage Of Angptl3, Robert L. Hanson, Fatjon Leti, Darwin Tsinajinnie, Sayuko Kobes, Sobha Puppala, Joanne E. Curran, Laura Almasy, Donna M. Lehman, John Blangero, Ravi Duggirala, Johanna K. Distefano

School of Medicine Publications and Presentations

We previously identified a locus linked to total cholesterol (TC) concentration in Pima Indians on chromosome 19p. To characterize this locus, we genotyped >2000 SNPs in 1838 Pimas and assessed association with log(TC). We observed evidence for association with log(TC) with rs2278426 (3.5% decrease/copy of the T allele; P=5.045×10(-6)) in the ANGPTL8 (angiopoietin-like 8) gene. We replicated this association in 2413 participants of the San Antonio Mexican American Family Study (SAMAFS: 2.0% decrease per copy of the T allele; P=0.005842). In a meta-analysis of the combined data, we found the strongest estimated effect with rs2278426 (P=2.563×10(-7)). The variant T allele …

Genome-Wide Association Studies Suggest Sex-Specific Loci Associated With Abdominal And Visceral Fat, Yun Ju Sung, L. Pérusse, M. A. Sarzynski, M. Fornage, S. Sidney, B. Sternfeld, T. Rice, J. G. Terry, D. R. Jacobs Jr., John Blangero, Joanne E. Curran

School of Medicine Publications and Presentations

Background:

To identify loci associated with abdominal fat and replicate prior findings, we performed genome-wide association (GWA) studies of abdominal fat traits: subcutaneous adipose tissue (SAT); visceral adipose tissue (VAT); total adipose tissue (TAT) and visceral to subcutaneous adipose tissue ratio (VSR).

Subjects and Methods:

Sex-combined and sex-stratified analyses were performed on each trait with (TRAIT–BMI) or without (TRAIT) adjustment for body mass index (BMI), and cohort-specific results were combined via a fixed effects meta-analysis. A total of 2513 subjects of European descent were available for the discovery phase. For replication, 2171 European Americans and 772 African Americans were available. …

Lipidomic Risk Score Independently And Cost-Effectively Predicts Risk Of Future Type 2 Diabetes: Results From Diverse Cohorts, Manju Mamtani, Hemant Kulkarni, Gerard Wong, Jacquelyn M. Weir, Christopher K. Barlow, Thomas D. Dyer, Laura Almasy, Michael C. Mahaney, Anthony G. Comuzzie, David C. Glahn, Sarah Williams-Blangero, Ravindranath Duggirala, John Blangero, Joanne E. Curran

School of Medicine Publications and Presentations

Background: Detection of type 2 diabetes (T2D) is routinely based on the presence of dysglycemia. Although disturbed lipid metabolism is a hallmark of T2D, the potential of plasma lipidomics as a biomarker of future T2D is unknown. Our objective was to develop and validate a plasma lipidomic risk score (LRS) as a biomarker of future type 2 diabetes and to evaluate its cost-effectiveness for T2D screening.

Methods: Plasma LRS, based on significantly associated lipid species from an array of 319 lipid species, was developed in a cohort of initially T2D-free individuals from the San Antonio Family Heart Study (SAFHS). The …

Shared Genetic Variance Between Obesity And White Matter Integrity In Mexican Americans, Elena A. Spieker, Peter Kochunov, Laura M. Rowland, Emma Sprooten, Anderson M. Winkler, Rene L. Olvera, Laura Almasy, Ravi Duggirala, Peter T. Fox, John Blangero, David C. Glahn, Joanne E. Curran

School of Medicine Publications and Presentations

Obesity is a chronic metabolic disorder that may also lead to reduced white matter integrity, potentially due to shared genetic risk factors. Genetic correlation analyses were conducted in a large cohort of Mexican American families in San Antonio (N = 761, 58% females, ages 18–81 years; 41.3 ± 14.5) from the Genetics of Brain Structure and Function Study. Shared genetic variance was calculated between measures of adiposity [(body mass index (BMI; kg/m2) and waist circumference (WC; in)] and whole-brain and regional measurements of cerebral white matter integrity (fractional anisotropy). Whole-brain average and regional fractional anisotropy values for 10 major …

The Enigma Consortium: Large-Scale Collaborative Analyses Of Neuroimaging And Genetic Data, Paul M. Thompson, Jason L. Stein, Laura Almasy, Anderson M. Winkler, John Blangero, Joanne E. Curran, Ravi Duggirala, Thomas D. Dyer, Harald H. H. Goring, Peter T. Fox

School of Medicine Publications and Presentations

The Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium is a collaborative network of researchers working together on a range of large-scale studies that integrate data from 70 institutions worldwide. Organized into Working Groups that tackle questions in neuroscience, genetics, and medicine, ENIGMA studies have analyzed neuroimaging data from over 12,826 subjects. In addition, data from 12,171 individuals were provided by the CHARGE consortium for replication of findings, in a total of 24,997 subjects. By meta-analyzing results from many sites, ENIGMA has detected factors that affect the brain that no individual site could detect on its own, and that require larger …

Genetic Influence On The Working Memory Circuitry: Behavior, Structure, Function And Extensions To Illness, Katherine H. Karlsgodt, Peter Bachman, Anderson M. Winkler, Carrie E. Bearden, David C. Glahn

School of Medicine Publications and Presentations

Working memory is a highly heritable complex cognitive trait that is critical for a number of higher-level functions. However, the neural substrates of this behavioral phenotype are intricate and it is unknown through what precise biological mechanism variation in working memory is transmitted. In this review we explore different functional and structural components of the working memory circuitry, and the degree to which each of them is contributed to by genetic factors. Specifically, we consider dopaminergic function, glutamatergic function, white matter integrity and gray matter structure all of which provide potential mechanisms for the inheritance of working memory deficits. In …

Blood Pressure And Cerebral White Matter Share Common Genetic Factors In Mexican Americans, Peter Kochunov, David C. Glahn, Jack Lancaster, Anderson M. Winkler, Rene L. Olvera, Joanne E. Curran, Thomas D. Dyer, Laura Almasy, Ravi Duggirala, Peter T. Fox, John Blangero

School of Medicine Publications and Presentations

Elevated arterial pulse pressure and blood pressure (BP) can lead to atrophy of cerebral white matter (WM), potentially attributable to shared genetic factors. We calculated the magnitude of shared genetic variance between BP and fractional anisotropy of water diffusion, a sensitive measurement of WM integrity in a well-characterized population of Mexican Americans. The patterns of whole-brain and regional genetic overlap between BP and fractional anisotropy were interpreted in the context the pulse-wave encephalopathy theory. We also tested whether regional pattern in genetic pleiotropy is modulated by the phylogeny of WM development. BP and high-resolution (1.7 × 1.7 × 3 mm; …