Code and summary statistics for "Imputation of fluid intelligence scores reduces ascertainment bias and increases power for analyses of common and rare variants"

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This repository contains code and summary statistics used in the article "Imputation of fluid intelligence scores reduces ascertainment bias and increases power for analyses of common and rare variants" Please also find the General Lay Summary and Frequently Asked Questions we wrote to accompany the article and contents of this repositoryThe code requires data fields obtained from UK Biobank, access to which is restricted to UK Biobank approved researchers. We also include code that is written to run on the UKB RAP. The summary statistics are divided in two folders: i) population GWAS: summary statistics from a standard GWAS run using Regenie ii) within-family GWAS: summary statistics from a within-family GWAS run using snipar Both folders contain raw summary statistics and summary statistics prepared for LDSC. Files are named according to the following glossary: Abbreviation Description Observed FIS1 UKB baseline measured FIS (20016-0.0) earliest observed FIS Earliest measured FIS across 5 measured tests Observed FIS Average measured FIS across 5 measured tests imputed average FIS Imputed FIS only, from imputation using the average of available FIS measures imputed earliest FIS Imputed FIS only, from imputation using the earliest of available FIS measures imputed All5 FIS Imputed FIS only, from imputation using the all 5 available FIS measures MegaFIS-vA Mega analysis of FIS1 and Imputed FIS1 using 154 imputation variables MegaFIS-vB Mega analysis of Observed FIS1 and Imputed FIS1 using 82 variables Combined FIS Mega analysis of Average observed FIS and imputed average FIS MegaFIS-earliest Mega analysis of Earliest observed FIS and imputed earliest FIS MegaFIS-all5 Mega analysis of FIS1 and imputed All5 FIS Please find below the abstract of our article:Studying the genetics of intelligence provides insight into the neurobiology of cognitive function and rare neurodevelopmental conditions. Here, we integrated fluid intelligence (FI) tests across different UK Biobank measures, and imputed FI for unmeasured individuals, increasing the sample size from ~270k to >455k. We show through extensive validation that the imputed phenotype genetically resembles measured FI, though some non-cognitive signal likely remains. Combining measured and imputed FI increases the number of independent significant common SNP associations from 390 to 550, and reduces the ascertainment bias introduced by FI test participants being, on average, more educated. Rare variant analyses identify twenty-six significantly associated genes (FDR<1%), including eight without strong prior evidence of involvement in intelligence or neurodevelopmental conditions, which replicate in aggregate in external cohorts. Our results demonstrate that imputed intelligence can boost power for genetic discovery, and support its use to help discover novel neurodevelopmental condition-associated genes.