Genetic correlations and genome-wide associations of cortical structure in general population samples of 22,824 adults

Published on Sep 22, 2020in Nature Communications12.121
· DOI :10.1038/S41467-020-18367-Y
Edith Hofer27
Estimated H-index: 27
(Medical University of Graz),
Gennady V. Roshchupkin10
Estimated H-index: 10
(EUR: Erasmus University Rotterdam)
+ 96 AuthorsSudha Seshadri95
Estimated H-index: 95
(BU: Boston University)
#1Katrina L. Grasby (QIMR: QIMR Berghofer Medical Research Institute)H-Index: 10
#2Neda Jahanshad (SC: University of Southern California)H-Index: 48
Last. Sarah E. Medland (QIMR: QIMR Berghofer Medical Research Institute)H-Index: 85
view all 362 authors...
INTRODUCTION The cerebral cortex underlies our complex cognitive capabilities. Variations in human cortical surface area and thickness are associated with neurological, psychological, and behavioral traits and can be measured in vivo by magnetic resonance imaging (MRI). Studies in model organisms have identified genes that influence cortical structure, but little is known about common genetic variants that affect human cortical structure. RATIONALE To identify genetic variants associated with hu...
85 CitationsSource
#2Thomas E. Nichols (University of Oxford)H-Index: 79
Last. Anderson M. Winkler (NIH: National Institutes of Health)H-Index: 35
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The multiple testing problem arises not only when there are many voxels or vertices in an image representation of the brain, but also when multiple contrasts of parameter estimates (that represent hypotheses) are tested in the same general linear model. We argue that a correction for this multiplicity must be performed to avoid excess of false positives. Various methods for correction have been proposed in the literature, but few have been applied to brain imaging. Here we discuss and compare di...
6 CitationsSource
#1Sven J. van der Lee (EUR: Erasmus University Rotterdam)H-Index: 33
#2Maria J. Knol (EUR: Erasmus University Rotterdam)H-Index: 6
Last. Charles DeCarli (UC Davis: University of California, Davis)H-Index: 113
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Brain lobar volumes are heritable but genetic studies are limited. We performed genome-wide association studies of frontal, occipital, parietal and temporal lobe volumes in 16,016 individuals, and replicated our findings in 8,789 individuals. We identified six genetic loci associated with specific lobar volumes independent of intracranial volume. Two loci, associated with occipital (6q22.32) and temporal lobe volume (12q14.3), were previously reported to associate with intracranial and hippocamp...
8 CitationsSource
#1Bingxin Zhao (UNC: University of North Carolina at Chapel Hill)H-Index: 4
#2Tianyou Luo (UNC: University of North Carolina at Chapel Hill)H-Index: 3
Last. Hongtu Zhu (UNC: University of North Carolina at Chapel Hill)H-Index: 4
view all 12 authors...
Volumetric variations of the human brain are heritable and are associated with many brain-related complex traits. Here we performed genome-wide association studies (GWAS) of 101 brain volumetric phenotypes using the UK Biobank sample including 19,629 participants. GWAS identified 365 independent genetic variants exceeding a significance threshold of 4.9 × 10−10, adjusted for testing multiple phenotypes. A gene-based association study found 157 associated genes (124 new), and functional gene mapp...
40 CitationsSource
#1Shing Wan Choi (ISMMS: Icahn School of Medicine at Mount Sinai)H-Index: 11
#2Paul F. O'Reilly (ISMMS: Icahn School of Medicine at Mount Sinai)H-Index: 45
BACKGROUND: Polygenic risk score (PRS) analyses have become an integral part of biomedical research, exploited to gain insights into shared aetiology among traits, to control for genomic profile in experimental studies, and to strengthen causal inference, among a range of applications. Substantial efforts are now devoted to biobank projects to collect large genetic and phenotypic data, providing unprecedented opportunity for genetic discovery and applications. To process the large-scale data pro...
159 CitationsSource
#1Marguerite R. Irvin (UAB: University of Alabama at Birmingham)H-Index: 33
#2Colleen M. Sitlani (UW: University of Washington)H-Index: 20
Last. Leslie A. Lange (Anschutz Medical Campus)H-Index: 59
view all 26 authors...
We evaluated interactions of SNP-by-ACE-I/ARB and SNP-by-TD on serum potassium (K+) among users of antihypertensive treatments (anti-HTN). Our study included seven European-ancestry (EA) (N = 4835) and four African-ancestry (AA) cohorts (N = 2016). We performed race-stratified, fixed-effect, inverse-variance-weighted meta-analyses of 2.5 million SNP-by-drug interaction estimates; race-combined meta-analysis; and trans-ethnic fine-mapping. Among EAs, we identified 11 significant SNPs (P < 5 × 10−...
3 CitationsSource
#1Lloyd T. Elliott (University of Oxford)H-Index: 10
#2Kevin Sharp (University of Oxford)H-Index: 9
Last. Stephen M. Smith (University of Oxford)H-Index: 115
view all 8 authors...
The genetic architecture of brain structure and function is largely unknown. To investigate this, we carried out genome-wide association studies of 3,144 functional and structural brain imaging phenotypes from UK Biobank (discovery dataset 8,428 subjects). Here we show that many of these phenotypes are heritable. We identify 148 clusters of associations between single nucleotide polymorphisms and imaging phenotypes that replicate at P < 0.05, when we would expect 21 to replicate by chance. Notab...
217 CitationsSource
#1Gail Davies (Edin.: University of Edinburgh)H-Index: 60
#2Max LamH-Index: 16
Last. Ian J. Deary (Edin.: University of Edinburgh)H-Index: 21
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General cognitive function is a prominent and relatively stable human trait that is associated with many important life outcomes. We combine cognitive and genetic data from the CHARGE and COGENT consortia, and UK Biobank (total N = 300,486; age 16–102) and find 148 genome-wide significant independent loci (P < 5 × 10−8) associated with general cognitive function. Within the novel genetic loci are variants associated with neurodegenerative and neurodevelopmental disorders, physical and psychiatri...
200 CitationsSource
#1Suneetha Uppu (Curtin University)H-Index: 5
#2Aneesh Krishna (Curtin University)H-Index: 13
Last. Raj P. Gopalan (Curtin University)H-Index: 11
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In this era of genome-wide association studies (GWAS), the quest for understanding the genetic architecture of complex diseases is rapidly increasing more than ever before. The development of high throughput genotyping and next generation sequencing technologies enables genetic epidemiological analysis of large scale data. These advances have led to the identification of a number of single nucleotide polymorphisms (SNPs) responsible for disease susceptibility. The interactions between SNPs assoc...
24 CitationsSource
#1Michelle Luciano (Edin.: University of Edinburgh)H-Index: 52
#2Saskia P. Hagenaars (Edin.: University of Edinburgh)H-Index: 26
Last. Ian J. Deary (Edin.: University of Edinburgh)H-Index: 21
view all 16 authors...
Neuroticism is a relatively stable personality trait characterized by negative emotionality (for example, worry and guilt)1; heritability estimated from twin studies ranges from 30 to 50%2, and SNP-based heritability ranges from 6 to 15%3–6. Increased neuroticism is associated with poorer mental and physical health7,8, translating to high economic burden9. Genome-wide association studies (GWAS) of neuroticism have identified up to 11 associated genetic loci3,4. Here we report 116 significant ind...
170 CitationsSource
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