Intracranial Volume Is Driven by Both Genetics and Early Life Exposures: The SOL-INCA-MRI Study

Author:

Sofer Tamar123,Granot-Hershkovitz Einat1,Tarraf Wassim4,Filigrana Paola5,Isasi Carmen R.6,Suglia Shakira F.7,Kaplan Robert68,Taylor Kent9,Daviglus Martha L.10,Testai Fernando D.11,Zeng Donglin12,Cai Jianwen12,Fornage Myriam13,González Hector M.14,DeCarli Charles15

Affiliation:

1. 1 Division of Sleep and Circadian Disorders, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA

2. 2 CardioVascular Institute, Beth Israel Deaconess Medical Center, Boston, MA

3. 3 Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA

4. 4 Institute of Gerontology, Wayne State University, Detroit, MI

5. 5 Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY

6. 6 Department of Epidemiology & Population Health, Department of Pediatrics, Albert Einstein College of Medicine, Bronx, NY

7. 7 Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA

8. 8 Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle WA

9. 9 The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA

10. 10 Department of Medicine, Institute for Minority Health Research, University of Illinois at Chicago, IL

11. 11 Department of Neurology, University of Illinois at Chicago College of Medicine, Chicago, IL

12. 12 Department of Biostatistics, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC

13. 13 Brown Foundation Institute of Molecular Medicine, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX

14. 14 Department of Neurosciences and Shiley-Marcos Alzheimer’s Disease Center, University of California, San Diego, La Jolla, CA

15. 15 Alzheimer’s Disease Research Center, Department of Neurology, University of California, Davis, Sacramento, CA

Abstract

Intracranial volume (ICV) reflects maximal brain development and is associated with later-life cognitive abilities. We quantified ICV among first- and second-generation Hispanic and Latino adults from the Study of Latinos-Investigation of Cognitive Aging – MRI (SOL-INCA-MRI), estimated ICV heritability, and tested its associations with previously reported genetic variants, both individually and as a genetic risk score (GRS). We also estimated the association of ICV with early life environmental measures: nativity or age of immigration and parental education. The estimated heritability of ICV was 19% (95% CI, 0.1%-56%) in n=1781 unrelated SOL-INCA-MRI individuals. Four of 10 tested genetic variants were associated with ICV and an increase of 1 SD of the ICV-GRS was associated with an increase of 10.37 cm3 in the ICV (95% CI, 5.29-15.45). Compared to being born in the continental United States, immigrating to the United States at age 11 years or older was associated with 24 cm3 smaller ICV (95% CI, −39.97 to −8.06). Compared to both parents having less than high-school education, at least 1 parent completing high-school education was associated with 15.4 cm3 greater ICV (95% CI, 4.46-26.39). These data confirm the importance of early life health on brain development.

Publisher

Ethnicity and Disease Inc

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