publication . Preprint . 2019

GWAS of 19,629 individuals identifies novel genetic variants for regional brain volumes and refines their genetic co-architecture with cognitive and mental health traits

Zhao, Bingxin; Luo, Tianyou; Li, Tengfei; Li, Yun; Zhang, Jingwen; Shan, Yue; Wang, Xifeng; Yang, Liuqing; Zhou, Fan; Zhu, Ziliang; ...
Open Access
  • Published: 25 Mar 2019
  • Publisher: Cold Spring Harbor Laboratory
Abstract
<jats:title>Abstract</jats:title><jats:p>Volumetric variations of human brain are heritable and are associated with many brain-related complex traits. Here we performed genome-wide association studies (GWAS) and post-GWAS analyses of 101 brain volumetric phenotypes using the UK Biobank (UKB) sample including 19,629 participants. GWAS identified 287 independent SNPs exceeding genome-wide significance threshold of 4.9*10<jats:sup>−10</jats:sup>, adjusted for testing multiple phenotypes. Gene-based association study found 142 associated genes (113 new) and functional gene mapping analysis linked 122 more genes. Many of the discovered genetic variants have previousl...
Subjects
free text keywords: Biology, Locus (genetics), Genetic association, Sample size determination, Pleiotropy, Single-nucleotide polymorphism, Gene mapping, Genome-wide association study, Genetics, SNP
Funded by
CIHR
Project
  • Funder: Canadian Institutes of Health Research (CIHR)
,
NIH| Alzheimers Disease Neuroimaging Initiative
Project
  • Funder: National Institutes of Health (NIH)
  • Project Code: 1U01AG024904-01
  • Funding stream: NATIONAL INSTITUTE ON AGING
,
NIH| Neurodevelopmental Genomics: Trajectories of Complex Phenotypes
Project
  • Funder: National Institutes of Health (NIH)
  • Project Code: 5RC2MH089983-02
  • Funding stream: NATIONAL INSTITUTE OF MENTAL HEALTH
,
NIH| Mapping the Human Connectome: Structure, Function, and Heritability
Project
  • Funder: National Institutes of Health (NIH)
  • Project Code: 3U54MH091657-03S1
  • Funding stream: NATIONAL INSTITUTE OF MENTAL HEALTH
,
NIH| Creating a Pediatric Imaging-Genomics Data Resource
Project
  • Funder: National Institutes of Health (NIH)
  • Project Code: 3RC2DA029475-02S1
  • Funding stream: NATIONAL INSTITUTE ON DRUG ABUSE
65 references, page 1 of 5

1. Ritchie SJ, Booth T, Hernández MdCV, Corley J, Maniega SM, Gow AJ, et al. Beyond a bigger brain: Multivariable structural brain imaging and intelligence. Intelligence. 2015;51:47-56. [OpenAIRE]

2. Davies G, Marioni RE, Liewald DC, Hill WD, Hagenaars SP, Harris SE, et al. Genome-wide association study of cognitive functions and educational attainment in UK Biobank (N= 112 151). Molecular psychiatry. 2016;21(6):758.

3. van der Meer D, Rokicki J, Kaufmann T, Palomera AC, Moberget T, Alnaes D, et al. Brain scans from 21297 individuals reveal the genetic architecture of hippocampal subfield volumes. bioRxiv. 2018:299578. [OpenAIRE]

4. Caldiroli A, Buoli M, van Haren NE, de Nijs J, Altamura AC, Cahn W. The relationship of IQ and emotional processing with insula volume in schizophrenia. Schizophrenia research. 2018;202:141-8.

5. Vreeker A, Abramovic L, Boks MP, Verkooijen S, van Bergen AH, Ophoff RA, et al. The relationship between brain volumes and intelligence in bipolar disorder. Journal of affective disorders. 2017;223:59-64. [OpenAIRE]

6. Wigmore EM, Clarke T-K, Howard D, Adams M, Hall L, Zeng Y, et al. Do regional brain volumes and major depressive disorder share genetic architecture? A study of Generation Scotland (n= 19 762), UK Biobank (n= 24 048) and the English Longitudinal Study of Ageing (n= 5766). Translational psychiatry. 2017;7(8):e1205.

7. Elliott LT, Sharp K, Alfaro-Almagro F, Shi S, Miller KL, Douaud G, et al. Genome-wide association studies of brain imaging phenotypes in UK Biobank. Nature. 2018;562(7726):210.

8. Hibar DP, Stein JL, Renteria ME, Arias-Vasquez A, Desrivières S, Jahanshad N, et al. Common genetic variants influence human subcortical brain structures. Nature. 2015;520(7546):224.

9. Blokland GA, de Zubicaray GI, McMahon KL, Wright MJ. Genetic and environmental influences on neuroimaging phenotypes: a meta-analytical perspective on twin imaging studies. Twin Research and Human Genetics. 2012;15(3):351-71.

10. Zhao B, Ibrahim JG, Li Y, Li T, Wang Y, Shan Y, et al. Heritability of regional brain volumes in large-scale neuroimaging and genetic studies. bioRxiv. 2017:208496.

11. Boyle EA, Li YI, Pritchard JK. An Expanded View of Complex Traits: From Polygenic to Omnigenic. Cell. 2017;169(7):1177-86.

12. Timpson NJ, Greenwood CM, Soranzo N, Lawson DJ, Richards JB. Genetic architecture: the shape of the genetic contribution to human traits and disease. Nature Reviews Genetics. 2017. [OpenAIRE]

13. Zhao B, Zhu H. On genetic correlation estimation with summary statistics from genome-wide association studies. arXiv. 2019:arXiv:1903.01301.

14. Hibar DP, Adams HH, Jahanshad N, Chauhan G, Stein JL, Hofer E, et al. Novel genetic loci associated with hippocampal volume. Nature communications. 2017;8:13624. [OpenAIRE]

15. Franke B, Stein JL, Ripke S, Anttila V, Hibar DP, Van Hulzen KJ, et al. Genetic influences on schizophrenia and subcortical brain volumes: large-scale proof of concept. Nature neuroscience. 2016;19(3):420-31.

65 references, page 1 of 5
Abstract
<jats:title>Abstract</jats:title><jats:p>Volumetric variations of human brain are heritable and are associated with many brain-related complex traits. Here we performed genome-wide association studies (GWAS) and post-GWAS analyses of 101 brain volumetric phenotypes using the UK Biobank (UKB) sample including 19,629 participants. GWAS identified 287 independent SNPs exceeding genome-wide significance threshold of 4.9*10<jats:sup>−10</jats:sup>, adjusted for testing multiple phenotypes. Gene-based association study found 142 associated genes (113 new) and functional gene mapping analysis linked 122 more genes. Many of the discovered genetic variants have previousl...
Subjects
free text keywords: Biology, Locus (genetics), Genetic association, Sample size determination, Pleiotropy, Single-nucleotide polymorphism, Gene mapping, Genome-wide association study, Genetics, SNP
Funded by
CIHR
Project
  • Funder: Canadian Institutes of Health Research (CIHR)
,
NIH| Alzheimers Disease Neuroimaging Initiative
Project
  • Funder: National Institutes of Health (NIH)
  • Project Code: 1U01AG024904-01
  • Funding stream: NATIONAL INSTITUTE ON AGING
,
NIH| Neurodevelopmental Genomics: Trajectories of Complex Phenotypes
Project
  • Funder: National Institutes of Health (NIH)
  • Project Code: 5RC2MH089983-02
  • Funding stream: NATIONAL INSTITUTE OF MENTAL HEALTH
,
NIH| Mapping the Human Connectome: Structure, Function, and Heritability
Project
  • Funder: National Institutes of Health (NIH)
  • Project Code: 3U54MH091657-03S1
  • Funding stream: NATIONAL INSTITUTE OF MENTAL HEALTH
,
NIH| Creating a Pediatric Imaging-Genomics Data Resource
Project
  • Funder: National Institutes of Health (NIH)
  • Project Code: 3RC2DA029475-02S1
  • Funding stream: NATIONAL INSTITUTE ON DRUG ABUSE
65 references, page 1 of 5

1. Ritchie SJ, Booth T, Hernández MdCV, Corley J, Maniega SM, Gow AJ, et al. Beyond a bigger brain: Multivariable structural brain imaging and intelligence. Intelligence. 2015;51:47-56. [OpenAIRE]

2. Davies G, Marioni RE, Liewald DC, Hill WD, Hagenaars SP, Harris SE, et al. Genome-wide association study of cognitive functions and educational attainment in UK Biobank (N= 112 151). Molecular psychiatry. 2016;21(6):758.

3. van der Meer D, Rokicki J, Kaufmann T, Palomera AC, Moberget T, Alnaes D, et al. Brain scans from 21297 individuals reveal the genetic architecture of hippocampal subfield volumes. bioRxiv. 2018:299578. [OpenAIRE]

4. Caldiroli A, Buoli M, van Haren NE, de Nijs J, Altamura AC, Cahn W. The relationship of IQ and emotional processing with insula volume in schizophrenia. Schizophrenia research. 2018;202:141-8.

5. Vreeker A, Abramovic L, Boks MP, Verkooijen S, van Bergen AH, Ophoff RA, et al. The relationship between brain volumes and intelligence in bipolar disorder. Journal of affective disorders. 2017;223:59-64. [OpenAIRE]

6. Wigmore EM, Clarke T-K, Howard D, Adams M, Hall L, Zeng Y, et al. Do regional brain volumes and major depressive disorder share genetic architecture? A study of Generation Scotland (n= 19 762), UK Biobank (n= 24 048) and the English Longitudinal Study of Ageing (n= 5766). Translational psychiatry. 2017;7(8):e1205.

7. Elliott LT, Sharp K, Alfaro-Almagro F, Shi S, Miller KL, Douaud G, et al. Genome-wide association studies of brain imaging phenotypes in UK Biobank. Nature. 2018;562(7726):210.

8. Hibar DP, Stein JL, Renteria ME, Arias-Vasquez A, Desrivières S, Jahanshad N, et al. Common genetic variants influence human subcortical brain structures. Nature. 2015;520(7546):224.

9. Blokland GA, de Zubicaray GI, McMahon KL, Wright MJ. Genetic and environmental influences on neuroimaging phenotypes: a meta-analytical perspective on twin imaging studies. Twin Research and Human Genetics. 2012;15(3):351-71.

10. Zhao B, Ibrahim JG, Li Y, Li T, Wang Y, Shan Y, et al. Heritability of regional brain volumes in large-scale neuroimaging and genetic studies. bioRxiv. 2017:208496.

11. Boyle EA, Li YI, Pritchard JK. An Expanded View of Complex Traits: From Polygenic to Omnigenic. Cell. 2017;169(7):1177-86.

12. Timpson NJ, Greenwood CM, Soranzo N, Lawson DJ, Richards JB. Genetic architecture: the shape of the genetic contribution to human traits and disease. Nature Reviews Genetics. 2017. [OpenAIRE]

13. Zhao B, Zhu H. On genetic correlation estimation with summary statistics from genome-wide association studies. arXiv. 2019:arXiv:1903.01301.

14. Hibar DP, Adams HH, Jahanshad N, Chauhan G, Stein JL, Hofer E, et al. Novel genetic loci associated with hippocampal volume. Nature communications. 2017;8:13624. [OpenAIRE]

15. Franke B, Stein JL, Ripke S, Anttila V, Hibar DP, Van Hulzen KJ, et al. Genetic influences on schizophrenia and subcortical brain volumes: large-scale proof of concept. Nature neuroscience. 2016;19(3):420-31.

65 references, page 1 of 5
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