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Trak2, A Novel Regulator Of Abca1 Expression, Cholesterol Efflux And Hdl Biogenesis, Nicole J. Lake, Rachael L. Taylor, Hugh Trahair, K. N. Harikrishnan, Joanne E. Curran, Marcio Almeida, Hemant Kulkarni, Matthew P. Johnson, Thomas D. Dyer, Michael Mahaney, Harald H. H. Goring, John Blangero

School of Medicine Publications and Presentations

Aims: The recent failures of HDL-raising therapies have underscored our incomplete understanding of HDL biology. Therefore there is an urgent need to comprehensively investigate HDL metabolism to enable the development of effective HDL-centric therapies. To identify novel regulators of HDL metabolism, we performed a joint analysis of human genetic, transcriptomic, and plasma HDL-cholesterol (HDL-C) concentration data and identified a novel association between trafficking protein, kinesin binding 2 (TRAK2) and HDL-C concentration. Here we characterize the molecular basis of the novel association between TRAK2 and HDL-cholesterol concentration.

Methods and results: Analysis of lymphocyte transcriptomic data together with plasma HDL from the …

The Lipidome In Major Depressive Disorder: Shared Genetic Influence For Ether-Phosphatidylcholines, A Plasma-Based Phenotype Related To Inflammation, And Disease Risk, Emma E. M. Knowles, Kevin Huynh, Peter J. Meikle, 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

Background

The lipidome is rapidly garnering interest in the field of psychiatry. Recent studies have implicated lipidomic changes across numerous psychiatric disorders. In particular there is growing evidence that the concentrations of several classes of lipids are altered in those diagnosed with MDD. However, for lipidomic abnormalities to be considered potential treatment targets for MDD (rather than secondary manifestations of the disease), a shared etiology between lipid concentrations and MDD should be demonstrated.

Methods

In a sample of 567 individuals from 37 extended pedigrees (average size 13.57 people, range = 3–80), we used mass-spectrometry lipidomic measures to evaluate the genetic …

Epigenetic Age Acceleration Assessed With Human White-Matter Images, Karen Hodgson, Melanie A. Carless, Hemant Kulkarni, Joanne E. Curran, Emma Sprooten, Emma E. Knowles, Samuel R. Mathias, Harald H. H. Goring, Nailin Yao, Rene L. Olvera, Laura Almasy, Ravindranath Duggirala, John Blangero, David C. Glahn

School of Medicine Publications and Presentations

The accurate estimation of age using methylation data has proved a useful and heritable biomarker, with acceleration in epigenetic age predicting a number of age-related phenotypes. Measures of white matter integrity in the brain are also heritable and highly sensitive to both normal and pathological aging processes across adulthood. We consider the phenotypic and genetic interrelationships between epigenetic age acceleration and white matter integrity in humans. Our goal was to investigate processes that underlie interindividual variability in age-related changes in the brain. Using blood taken from a Mexican-American extended pedigree sample (n = 628; age = 23.28-93.11 years), epigenetic …

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 …