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Complete Dissertation VU Research Portal Discovering the genetic architecture of the mind Karlsson Linnér, R. 2019 document version Publisher's PDF, also known as Version of record Link to publication in VU Research Portal citation for published version (APA) Karlsson Linnér, R. (2019). Discovering the genetic architecture of the mind: (Epi-)genome-wide association studies on human psychology and behavior. 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Oct. 2021 CNCR Amsterdam Discovering the genetic architecture of the mind – (Epi-)genome-wide association studies on human psychology and behavior Richard Karlsson Linnér Doctorate committee: Chair: Prof. Dr. August B. Smit Prof. Dr. Ralph Hertwig Prof. Dr. Sven Oskarsson Dr. Cornelius A. Rietveld Prof. Dr. Karin J. H. Verweij Paranymphs: Casper A. P. Burik Hyeokmoon Kweon Cover design: Cliff van Thillo Printing: Ridderprint BV ISBN 978-94-6375-379-1 Copyright © Richard Karlsson Linnér, 2019 All rights reserved. No part of this thesis may be reproduced, stored in a retrieval system, or transmitted in any form or by any means without prior permission of the holder of the copyright. VRIJE UNIVERSITEIT DISCOVERING THE GENETIC ARCHITECTURE OF THE MIND (Epi-)genome-wide association studies on human psychology and behavior ACADEMISCH PROEFSCHRIFT ter verkrijging van de graad Doctor aan de Vrije Universiteit Amsterdam, op gezag van de rector magnificus prof.dr. V. Subramaniam, in het openbaar te verdedigen ten overstaan van de promotiecommissie van de Faculteit der Bètawetenschappen op donderdag 6 juni 2019 om 9.45 uur in de aula van de universiteit, De Boelelaan 1105 door Richard Karlsson Linnér geboren te Kalmar Domk, Zweden promotoren: prof.dr. P.D. Koellinger prof.dr. D. Posthuma Contents PREFACE ....................................................................................................................................................... L CHAPTER 1 INTRODUCTION .................................................................................................................... 1 BACKGROUND............................................................................................................................................... 2 PURPOSE AND RESEARCH QUESTIONS ............................................................................................................. 6 THESIS DISPOSITION ...................................................................................................................................... 7 THE GENETIC ARCHITECTURE OF COMPLEX TRAITS ......................................................................................... 8 INTRODUCTION TO THE MAIN PHENOTYPES ................................................................................................... 10 INDIVIDUAL CONTRIBUTIONS ....................................................................................................................... 12 REFERENCES – PREFACE & CHAPTER 1 ........................................................................................................ 15 CHAPTER 2 GENOME-WIDE ASSOCIATION ANALYSES OF RISK TOLERANCE AND RISKY BEHAVIORS IN OVER ONE MILLION INDIVIDUALS IDENTIFY HUNDREDS OF LOCI AND SHARED GENETIC INFLUENCES ........................................................................................................... 25 ABSTRACT .................................................................................................................................................. 26 INTRODUCTION ........................................................................................................................................... 27 RESULTS ..................................................................................................................................................... 27 DISCUSSION ................................................................................................................................................ 33 AUTHORS – CHAPTER 2 ............................................................................................................................... 34 REFERENCES – CHAPTER 2........................................................................................................................... 35 FIGURES AND TABLES – CHAPTER 2.............................................................................................................. 38 CHAPTER 2 SUPPLEMENTARY METHODS.......................................................................................... 42 OVERVIEW OF MAIN GWAS ........................................................................................................................ 42 GENOTYPING AND IMPUTATION ................................................................................................................... 43 ASSOCIATION ANALYSES ............................................................................................................................. 43 MAIN REFERENCE PANEL ............................................................................................................................. 44 UK BIOBANK GENOTYPING ARRAYS............................................................................................................. 46 DESCRIPTION OF MAJOR STEPS IN QUALITY-CONTROL (QC) ANALYSES .......................................................... 47 META-ANALYSIS, ADJUSTMENT OF THE STANDARD ERRORS, AND TEST OF HETEROGENEITY OF EFFECT SIZES ACROSS COHORTS ........................................................................................................................................ 50 APPROXIMATELY INDEPENDENT LEAD SNPS, LOCI, AND CONDITIONAL ANALYSIS .......................................... 52 CHECK FOR LONG-RANGE LD REGIONS, CANDIDATE INVERSIONS, AND 1000 GENOMES STRUCTURAL VARIANTS .................................................................................................................................................................. 53 INVESTIGATION OF THE NOVELTY OF OUR GWAS ASSOCIATIONS .................................................................. 55 GWAS CATALOG LOOKUP ........................................................................................................................... 55 CROSS-LOOKUP OF GWAS RESULTS ............................................................................................................ 56 GENE ANNOTATION ..................................................................................................................................... 56 METHODS TO ESTIMATE GENOME-WIDE SNP HERITABILITY .......................................................................... 57 REFERENCES – CHAPTER 2 SUPPLEMENTARY METHODS ................................................................................ 59 CHAPTER 3 GENETIC VARIANTS ASSOCIATED WITH SUBJECTIVE WELL-BEING, DEPRESSIVE SYMPTOMS, AND NEUROTICISM IDENTIFIED THROUGH GENOME-WIDE ANALYSIS ................................................................................................................................................... 63 ABSTRACT .................................................................................................................................................. 64 INTRODUCTION ........................................................................................................................................... 65 RESULTS ..................................................................................................................................................... 66 DISCUSSION ................................................................................................................................................ 71 AUTHORS – CHAPTER 3 ............................................................................................................................... 73 REFERENCES – CHAPTER 3........................................................................................................................... 74 FIGURES AND TABLES – CHAPTER 3.............................................................................................................. 76 CHAPTER 4 AN EPIGENOME-WIDE ASSOCIATION STUDY META-ANALYSIS OF EDUCATIONAL ATTAINMENT ............................................................................................................... 81 ABSTRACT .................................................................................................................................................. 82 INTRODUCTION ........................................................................................................................................... 83 METHODS ..................................................................................................................................................
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