Multi-Trait Polygenic Prediction of Nicotine Dependence Pubblico

Abstract

The estimated heritability of nicotine dependence (ND) ranges 40-70%, but Polygenic Risk Scores (PRS) calculated for ND have limited utility using only tobacco use Genome-Wide Association Study (GWAS) summary statistics. We examined a multi-trait PRS model using known genetic correlates of ND liability and show incremental gains in accuracy and power.

Table of Contents

TABLE OF CONTENTS

INTRODUCTION .......................................................................................................... 1

EPIDEMIOLOGY OF TOBACCO/NICOTINE DEPENDENCE ................................................................. 1

ETIOLOGY OF TOBACCO/NICOTINE DEPENDENCE ........................................................................ 2

STUDY AIMS ........................................................................................................................ 5

METHODS .................................................................................................................. 6

IDENTIFICATION OF TRAITS TO PREDICT ND ................................................................................ 6

DISCOVERY SAMPLES ............................................................................................................. 7

Height ........................................................................................................................... 7

BMI ............................................................................................................................... 8

Cigarettes Per Day ........................................................................................................ 9

Depression .................................................................................................................... 9

Educational Attainment ............................................................................................. 10

Neuroticism ................................................................................................................ 11

Schizophrenia ............................................................................................................. 12

Self-Perceived Risk-Taking .......................................................................................... 13

TARGET SAMPLE DESCRIPTION AND QUALITY CONTROL .............................................................. 13

STATISTICAL ANALYSIS.......................................................................................................... 14

Development and Optimization of PRS ...................................................................... 14

Model Equations......................................................................................................... 16

Multivariate Logistic Regression of ND on PRS in Target Sample .............................. 16

RESULTS ................................................................................................................... 17

SINGLE-TRAIT PRS EFFECTS ON ND ....................................................................................... 17

CORRELATIONS BETWEEN SINGLE-TRAIT PRS ........................................................................... 18

MULTI-TRAIT LOGISTIC REGRESSION PRS EFFECTS ON ND ......................................................... 18

DISSCUSSION ............................................................................................................ 19

TABLES .................................................................................................................... 23

TABLE 1: DSM-IV NICOTINE DEPENDENCE CRITERIA ................................................................. 23

TABLE 2: SUMMARY OF TRAITS SELECTED FOR ANALYSES AND GWAS RESULTS .............................. 24

TABLE 3: SUMMARY OF RESULTS FROM SINGLE-TRAIT PRS ......................................................... 25

TABLE 4: HOLM ADJUSTED PRS CORRELATIONS ....................................................................... 26

TABLE 5: ADJUSTED R2 ESTIMATE FROM MULTI-TRAIT LOGISTIC REGRESSION PRS ......................... 27

TABLE 6: SUMMARY OF RESULTS FROM MULTI-TRAIT LOGISTIC REGRESSION PRS ........................... 27

FIGURES ................................................................................................................... 28

FIGURE 1........................................................................................................................... 28

FIGURE 2........................................................................................................................... 29

FIGURE 3........................................................................................................................... 30

FIGURE 4........................................................................................................................... 31

FIGURE 5........................................................................................................................... 32

FIGURE 6........................................................................................................................... 33

FIGURE 7........................................................................................................................... 34

FIGURE 8........................................................................................................................... 35

FIGURE 9........................................................................................................................... 36

BIBLIOGRAPHY ......................................................................................................... 37

About this Honors Thesis

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School	Emory College
Department	Neuroscience and Behavioral Biology
Degree	B.S.
Submission	Honors Thesis
Language	English
Research Field	Biology, Genetics Psychology, Behavioral
Parola chiave	Height Schizophrenia Neuroticism Educational Attainment Risk-Taking Body Mass Index Depression Behavioral Genetics Cigarettes per Day Nicotine Dependence Polygenic Risk Scores
Committee Chair / Thesis Advisor	Dr. Rohan Palmer, Emory University
Committee Members	Dr. David Weinshenker, Emory University Dr. Alicia Smith, Emory University

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