Genome-wide association meta-analysis of 78,308 individuals identifies new loci and genes influencing human intelligence
Year: 2017
Type: review
Abstract: Danielle Posthuma and colleagues perform a large meta-analysis for intelligence and determine genetic overlap with several neuropsychiatric and metabolic traits. They find 15 new significant loci and implicate 40 new genes, most of which are predominantly expressed in the brain. Intelligence is associated with important economic and health-related life outcomes1. Despite intelligence having substantial heritability2 (0.54) and a confirmed polygenic nature, initial genetic studies were mostly underpowered3,4,5. Here we report a meta-analysis for intelligence of 78,308 individuals. We identify 336 associated SNPs (METAL P < 5 × 10−8) in 18 genomic loci, of which 15 are new. Around half of the SNPs are located inside a gene, implicating 22 genes, of which 11 are new findings. Gene-based analyses identified an additional 30 genes (MAGMA P < 2.73 × 10−6), of which all but one had not been implicated previously. We show that the identified genes are predominantly expressed in brain tissue, and pathway analysis indicates the involvement of genes regulating cell development (MAGMA competitive P = 3.5 × 10−6). Despite the well-known difference in twin-based heritability2 for intelligence in childhood (0.45) and adulthood (0.80), we show substantial genetic correlation (rg = 0.89, LD score regression P = 5.4 × 10−29). These findings provide new insight into the genetic architecture of intelligence.
Source: Nature Genetics
DOI: 10.1038/ng.3869
Authors: Suzanne Sniekers, Sven Stringer, Kyoko Watanabe, Philip R Jansen, Jonathan R I Coleman, Eva Krapohl, Erdogan Taskesen, Anke R Hammerschlag, Aysu Okbay, Delilah Zabaneh, Najaf Amin, Gerome Breen, David Cesarini, Christopher F Chabris, William G Iacono, M Arfan Ikram, Magnus Johannesson, Philipp Koellinger, James J Lee, Patrik K E Magnusson, Matt McGue, Mike B Miller, William E R Ollier, Antony Payton, Neil Pendleton, Robert Plomin, Cornelius A Rietveld, Henning Tiemeier, Cornelia M van Duijn, Danielle Posthuma
Institutions: Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Erasmus MC, King's College London, South London and Maudsley NHS Foundation Trust, Amsterdam UMC Location Vrije Universiteit Amsterdam, Erasmus University Rotterdam, New York University, Union College, University of Minnesota, Stockholm School of Economics, Harvard University, Karolinska Institutet, University of Manchester, Manchester Academic Health Science Centre, Leiden University
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $12,690
Funders: Vrije Universiteit Amsterdam, Nederlandse Organisatie voor Wetenschappelijk Onderzoek, Medical Research Council, Biotechnology and Biological Sciences Research Council, National Institute on Alcohol Abuse and Alcoholism, National Institute on Aging, National Institute of Mental Health, National Institute on Drug Abuse, National Institute of Diabetes and Digestive and Kidney Diseases
Awards: Twin Study of Female Alcoholism and Other Disorders, G16286648, Interstitial Cystitis in Swedish Twins, Adolescent drinking and midlife outcomes: A prospective cotwin control study, G3446323281, Moderation of Genetic Effects on Substance Dependence by Childhood Maltreatment, Centre for Genomic Research: Genomics Hub Renewal, Origins of learning difficulties and behaviour problems: from behavioural genetics to behavioural genomics., G4957958659, A genome-wide association study of non-pathological cognitive ageing, Twin Study of ADHD, CD and Substance Abuse, NBER Training Program in Aging and Health Economics, A Longitudinal Study of Adopted Youth and Their Families, Substance Abuse & Behavioral Disinhibition: Integrating Genes & Environment, Twin Family Study of Vulnerability to Substance Abuse, Novel polygenic models for mental disorders: from risk detection to disease mechanism., Adult consequences of youth substance use: Twin study enriched for SUD risk, Twin Family Study of Vulnerability to Substance Abuse, Sibling Models of Adolescent Alcohol Use and Abuse, Research Training - Mental Health Behavior Genetics, G982024520
OpenAlex ID: W2940205897