Dataset Information

Common variants at 12q15 and 12q24 are associated with infant head circumference.

ABSTRACT: To identify genetic variants associated with head circumference in infancy, we performed a meta-analysis of seven genome-wide association studies (GWAS) (N = 10,768 individuals of European ancestry enrolled in pregnancy and/or birth cohorts) and followed up three lead signals in six replication studies (combined N = 19,089). rs7980687 on chromosome 12q24 (P = 8.1 × 10(-9)) and rs1042725 on chromosome 12q15 (P = 2.8 × 10(-10)) were robustly associated with head circumference in infancy. Although these loci have previously been associated with adult height, their effects on infant head circumference were largely independent of height (P = 3.8 × 10(-7) for rs7980687 and P = 1.3 × 10(-7) for rs1042725 after adjustment for infant height). A third signal, rs11655470 on chromosome 17q21, showed suggestive evidence of association with head circumference (P = 3.9 × 10(-6)). SNPs correlated to the 17q21 signal have shown genome-wide association with adult intracranial volume, Parkinson's disease and other neurodegenerative diseases, indicating that a common genetic variant in this region might link early brain growth with neurological disease in later life.

SUBMITTER: Taal HR

PROVIDER: S-EPMC3773913 | biostudies-literature | 2012 Apr

REPOSITORIES: biostudies-literature

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Common variants at 12q15 and 12q24 are associated with infant head circumference.

Taal H Rob HR Pourcain Beate St BS Thiering Elisabeth E Das Shikta S Mook-Kanamori Dennis O DO Warrington Nicole M NM Kaakinen Marika M Kreiner-Møller Eskil E Bradfield Jonathan P JP Freathy Rachel M RM Geller Frank F Guxens Mònica M Cousminer Diana L DL Kerkhof Marjan M Timpson Nicholas J NJ Ikram M Arfan MA Beilin Lawrence J LJ Bønnelykke Klaus K Buxton Jessica L JL Charoen Pimphen P Chawes Bo Lund Krogsgaard BLK Eriksson Johan J Evans David M DM Hofman Albert A Kemp John P JP Kim Cecilia E CE Klopp Norman N Lahti Jari J Lye Stephen J SJ McMahon George G Mentch Frank D FD Müller Martina M O'Reilly Paul F PF Prokopenko Inga I Rivadeneira Fernando F Steegers Eric A P EAP Sunyer Jordi J Tiesler Carla C Yaghootkar Hanieh H Breteler Monique M B MMB Debette Stephanie S Fornage Myriam M Gudnason Vilmundur V Launer Lenore J LJ van der Lugt Aad A Mosley Thomas H TH Seshadri Sudha S Smith Albert V AV Vernooij Meike W MW Blakemore Alexandra If AI Chiavacci Rosetta M RM Feenstra Bjarke B Fernandez-Benet Julio J Grant Struan F A SFA Hartikainen Anna-Liisa AL van der Heijden Albert J AJ Iñiguez Carmen C Lathrop Mark M McArdle Wendy L WL Mølgaard Anne A Newnham John P JP Palmer Lyle J LJ Palotie Aarno A Palotie Aarno A Pouta Annneli A Ring Susan M SM Sovio Ulla U Standl Marie M Uitterlinden Andre G AG Wichmann H-Erich HE Vissing Nadja Hawwa NH DeCarli Charles C van Duijn Cornelia M CM McCarthy Mark I MI Koppelman Gerard H GH Estivill Xavier X Hattersley Andrew T AT Melbye Mads M Bisgaard Hans H Pennell Craig E CE Widen Elisabeth E Hakonarson Hakon H Smith George Davey GD Heinrich Joachim J Jarvelin Marjo-Riitta MR Jaddoe Vincent W V VWV

Nature genetics 20120415 5

To identify genetic variants associated with head circumference in infancy, we performed a meta-analysis of seven genome-wide association studies (GWAS) (N = 10,768 individuals of European ancestry enrolled in pregnancy and/or birth cohorts) and followed up three lead signals in six replication studies (combined N = 19,089). rs7980687 on chromosome 12q24 (P = 8.1 × 10(-9)) and rs1042725 on chromosome 12q15 (P = 2.8 × 10(-10)) were robustly associated with head circumference in infancy. Although ...[more]

PMID: 22504419

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Project description:While head circumference (HC) has been related to intracranial volume and brain size, its association with cognitive function remains unclear. We sought to understand the relationship among various biological and socioeconomic risk factors, HC and cognitive development. We analysed data across resource-poor settings in Bangladesh, India, Nepal, Peru, South Africa and Tanzania from the Etiology, Risk Factors and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development longitudinal birth cohort study. Participating children were enrolled and followed up between 2009 and 2014. A final sample of 1210 children aged 0-24 months were included in the analyses. The main outcomes were HC for age Z-score and cognitive, gross motor and language scores from Bayley Scales of Infant Development-III tests. Length, weight and HC were measured monthly, and cognitive tests were administered at 6, 15 and 24 months of age. To disentangle the associations between risk factors and HC from linear growth and to distinguish the direct and indirect effects of these risk factors on cognitive function, we conducted mediation analysis using longitudinal models to account for all data measured during follow-up. Average HC-for-age Z-score (HCAZ) was -0.54 (95% CI -0.47 to -0.62) near birth and -1.01 (95% CI -0.94 to -1.08) at 24 months. Children with higher enrolment weight (p<0.0001), higher socioeconomic score (p=0.00037) and taller mothers (p=0.00084) had higher HCAZ at all ages, while enteropathogen infection (p=0.013) and more febrile episodes (p=0.013) were associated with lower HCAZ. The associations between HCAZ and enrolment weight-for-age, maternal height, socioeconomic status or pathogen burden were partly mediated through their associations with length-for-age. HCAZ showed no association with cognitive, gross motor or language skills at 6, 15 and 24 months of age. The main risk factors associated with HC are similar to those associated with body length, and HC is not related to cognitive function.

Dataset Information

Common variants at 12q15 and 12q24 are associated with infant head circumference.

Publications

Common variants at 12q15 and 12q24 are associated with infant head circumference.

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