Multi-Trait Polygenic Prediction of Nicotine Dependence 公开
Risner, Victoria (Spring 2019)
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
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