title: KCTD8 gene and brain growth in adverse intrauterine environment: a genome-wide association study.
abstract: The most dramatic growth of the human brain occurs in utero and during the first 2 years of postnatal life. Genesis of the cerebral cortex involves cell proliferation, migration, and apoptosis, all of which may be influenced by prenatal environment. Here, we show that variation in KCTD8 (potassium channel tetramerization domain 8) is associated with brain size in female adolescents (rs716890, P = 5.40 × 10(-09)). Furthermore, we found that the KCTD8 locus interacts with prenatal exposure to maternal cigarette smoking vis-à-vis cortical area and cortical folding: In exposed girls only, the KCTD8 locus explains up to 21% of variance. Using head circumference as a proxy of brain size at 7 years of age, we have replicated this gene-environment interaction in an independent sample. We speculate that KCTD8 might modulate adverse effects of smoking during pregnancy on brain development via apoptosis triggered by low intracellular levels of potassium, possibly reducing the number of progenitor cells.
authors.affiliation: Rotman Research Institute, University of Toronto, Toronto, Ontario M6A 2E1, Canada. tpaus@rotman-baycrest.on.ca
authors.forename: Tomás
authors.initials: T
authors.lastname: Paus
authors.forename: Manon
authors.initials: M
authors.lastname: Bernard
authors.forename: M Mallar
authors.initials: MM
authors.lastname: Chakravarty
authors.forename: George
authors.initials: G
authors.lastname: Davey Smith
authors.forename: Jesse
authors.initials: J
authors.lastname: Gillis
authors.forename: Anbarasu
authors.initials: A
authors.lastname: Lourdusamy
authors.forename: Melkaye G
authors.initials: MG
authors.lastname: Melka
authors.forename: Gabriel
authors.initials: G
authors.lastname: Leonard
authors.forename: Paul
authors.initials: P
authors.lastname: Pavlidis
authors.forename: Michel
authors.initials: M
authors.lastname: Perron
authors.forename: G Bruce
authors.initials: GB
authors.lastname: Pike
authors.forename: Louis
authors.initials: L
authors.lastname: Richer
authors.forename: Gunter
authors.initials: G
authors.lastname: Schumann
authors.forename: Nicholas
authors.initials: N
authors.lastname: Timpson
authors.forename: Roberto
authors.initials: R
authors.lastname: Toro
authors.forename: Suzanne
authors.initials: S
authors.lastname: Veillette
authors.forename: Zdenka
authors.initials: Z
authors.lastname: Pausova
mesh_terms: D000293:Adolescent; D000328:Adult; D000465:Algorithms; D000818:Animals; D001724:Birth Weight / Q000502:physiology; D001827:Body Height / Q000502:physiology; D001921:Brain / Q000196:embryology / Q000254:growth & development*; D002170:Canada / Q000453:epidemiology; D002540:Cerebral Cortex / Q000033:anatomy & histology; D002648:Child; D005260:Female; D005317:Fetal Growth Retardation / Q000235:genetics*; D055106:Genome-Wide Association Study; D005865:Gestational Age; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D051379:Mice; D010290:Parents; D011247:Pregnancy; D011248:Pregnancy Complications / Q000235:genetics; D011297:Prenatal Exposure Delayed Effects / Q000235:genetics*; D012907:Smoking / Q000009:adverse effects*; D044465:White People