title: Obesity gene NEGR1 associated with white matter integrity in healthy young adults.
abstract: Obesity is a crucial public health issue in developed countries, with implications for cardiovascular and brain health as we age. A number of commonly-carried genetic variants are associated with obesity. Here we aim to see whether variants in obesity-associated genes--NEGR1, FTO, MTCH2, MC4R, LRRN6C, MAP2K5, FAIM2, SEC16B, ETV5, BDNF-AS, ATXN2L, ATP2A1, KCTD15, and TNN13K--are associated with white matter microstructural properties, assessed by high angular resolution diffusion imaging (HARDI) in young healthy adults between 20 and 30 years of age from the Queensland Twin Imaging study (QTIM). We began with a multi-locus approach testing how a number of common genetic risk factors for obesity at the single nucleotide polymorphism (SNP) level may jointly influence white matter integrity throughout the brain and found a wide spread genetic effect. Risk allele rs2815752 in NEGR1 was most associated with lower white matter integrity across a substantial portion of the brain. Across the area of significance in the bilateral posterior corona radiata, each additional copy of the risk allele was associated with a 2.2% lower average FA. This is the first study to find an association between an obesity risk gene and differences in white matter integrity. As our subjects were young and healthy, our results suggest that NEGR1 has effects on brain structure independent of its effect on obesity.
authors: Imaging Genetics Center, Institute for Neuroimaging and Informatics, Keck School of Medicine of USC, Los Angeles, CA, USA.
authors: Emily L
authors: EL
authors: Dennis
authors: Imaging Genetics Center, Institute for Neuroimaging and Informatics, Keck School of Medicine of USC, Los Angeles, CA, USA.
authors: Neda
authors: N
authors: Jahanshad
authors: Imaging Genetics Center, Institute for Neuroimaging and Informatics, Keck School of Medicine of USC, Los Angeles, CA, USA.
authors: Meredith N
authors: MN
authors: Braskie
authors: Imaging Genetics Center, Institute for Neuroimaging and Informatics, Keck School of Medicine of USC, Los Angeles, CA, USA.
authors: Nicholus M
authors: NM
authors: Warstadt
authors: Imaging Genetics Center, Institute for Neuroimaging and Informatics, Keck School of Medicine of USC, Los Angeles, CA, USA.
authors: Derrek P
authors: DP
authors: Hibar
authors: Geffen School of Medicine, University of California, Los Angeles, CA, USA.
authors: Omid
authors: O
authors: Kohannim
authors: Imaging Genetics Center, Institute for Neuroimaging and Informatics, Keck School of Medicine of USC, Los Angeles, CA, USA.
authors: Talia M
authors: TM
authors: Nir
authors: Center for Advanced Imaging, Univ. of Queensland, Brisbane, Australia.
authors: Katie L
authors: KL
authors: McMahon
authors: School of Psychology, University of Queensland, Brisbane, Australia.
authors: Greig I
authors: GI
authors: de Zubicaray
authors: Queensland Institute of Medical Research, Brisbane, Australia.
authors: Grant W
authors: GW
authors: Montgomery
authors: Queensland Institute of Medical Research, Brisbane, Australia.
authors: Nicholas G
authors: NG
authors: Martin
authors: Imaging Genetics Center, Institute for Neuroimaging and Informatics, Keck School of Medicine of USC, Los Angeles, CA, USA.
authors: Arthur W
authors: AW
authors: Toga
authors: School of Psychology, University of Queensland, Brisbane, Australia; Queensland Institute of Medical Research, Brisbane, Australia.
authors: Margaret J
authors: MJ
authors: Wright
authors: Imaging Genetics Center, Institute for Neuroimaging and Informatics, Keck School of Medicine of USC, Los Angeles, CA, USA; Departments of Neurology, Psychiatry, Radiology, Engineering, and Ophthalmology, Keck School of Medicine of USC, Los Angeles, CA, USA. Electronic address: pthomp@usc.edu.
authors: Paul M
authors: PM
authors: Thompson
mesh_terms: D000328:Adult; D001921:Brain / Q000033:anatomy & histology* / Q000502:physiology*; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics*; D056324:Diffusion Tensor Imaging; D005260:Female; D058851:GPI-Linked Proteins / Q000235:genetics; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D009765:Obesity / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D066127:White Matter / Q000033:anatomy & histology* / Q000502:physiology*; D055815:Young Adult
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; D058851:GPI-Linked Proteins; C485559:NEGR1 protein, human
keywords: HARDI; SNP; diffusion tensor imaging; genetics; multi-locus; obesity