Verneri Anttila

Publications (22) View all

• Article: Probing the brain of comorbidity.

  Aarno Palotie, Mikko Kallela, Verneri Anttila
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  ABSTRACT: Inherited sleep disorders might provide insights for migraine pathophysiology (Brennan et al., this issue).
  Science translational medicine 05/2013; 5(183):183fs15. · 7.80 Impact Factor
• Article: Genome-wide Association and Longitudinal Analyses Reveal Genetic Loci Linking Pubertal Height Growth, Pubertal Timing, and Childhood Adiposity.

  Diana L Cousminer, Diane J Berry, Nicholas J Timpson, Wei Ang, Elisabeth Thiering, Enda Byrne, H Rob Taal, Ville Huikari, Jonathan P Bradfield, Marjan Kerkhof, [......], Joachim Heinrich, Craig E Pennell, Olli Raitakari, Johan G Eriksson, George Davey Smith, Elina Hyppönen, Marjo-Riitta Järvelin, Mark I McCarthy, Samuli Ripatti, Elisabeth Widén
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  ABSTRACT: The pubertal height growth spurt is a distinctive feature of childhood growth reflecting both the central onset of puberty and local growth factors. While little is known about the underlying genetics, growth variability during puberty correlates with adult risks for hormone-dependent cancer and adverse cardiometabolic health. The only gene so far associated with pubertal height growth, LIN28B, pleiotropically influences childhood growth, puberty, and cancer progression, pointing to shared underlying mechanisms.To discover genetic loci influencing pubertal height and growth and place them in context of overall growth and maturation, we performed genome-wide association (GWA) meta-analyses in up to 18,737 European samples utilizing longitudinally collected height measurements. We found significant associations (P<1.67 x 10-8) at 10 loci, including LIN28B. Five loci associated with pubertal timing, all impacting multiple aspects of growth. In particular, a novel variant correlated with expression of MAPK3, and associated both with increased prepubertal growth and earlier menarche. Another variant near ADCY3-POMC associated with increased BMI, reduced pubertal growth, and earlier puberty.While epidemiological correlations suggest that early puberty marks a pathway from rapid prepubertal growth to reduced final height and adult obesity, our study shows that individual loci associating with pubertal growth have variable longitudinal growth patterns that may differ from epidemiological observations. Overall this study uncovers part of the complex genetic architecture linking pubertal height growth, the timing of puberty, and childhood obesity, and provides new information to pinpoint processes linking these traits.
  Human Molecular Genetics 02/2013; · 7.64 Impact Factor
• Article: Genome-wide association analysis identifies susceptibility loci for migraine without aura.

  Tobias Freilinger, Verneri Anttila, Boukje de Vries, Rainer Malik, Mikko Kallela, Gisela M Terwindt, Patricia Pozo-Rosich, Bendik Winsvold, Dale R Nyholt, Willebrordus P J van Oosterhout, [......], Thomas Meitinger, Bertram Müller-Myhsok, John-Anker Zwart, Markus Färkkilä, Alfons Macaya, Michel D Ferrari, Christian Kubisch, Aarno Palotie, Martin Dichgans, Arn M J M van den Maagdenberg
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  ABSTRACT: Migraine without aura is the most common form of migraine, characterized by recurrent disabling headache and associated autonomic symptoms. To identify common genetic variants associated with this migraine type, we analyzed genome-wide association data of 2,326 clinic-based German and Dutch individuals with migraine without aura and 4,580 population-matched controls. We selected SNPs from 12 loci with 2 or more SNPs associated with P values of <1 × 10(-5) for replication testing in 2,508 individuals with migraine without aura and 2,652 controls. SNPs at two of these loci showed convincing replication: at 1q22 (in MEF2D; replication P = 4.9 × 10(-4); combined P = 7.06 × 10(-11)) and at 3p24 (near TGFBR2; replication P = 1.0 × 10(-4); combined P = 1.17 × 10(-9)). In addition, SNPs at the PHACTR1 and ASTN2 loci showed suggestive evidence of replication (P = 0.01; combined P = 3.20 × 10(-8) and P = 0.02; combined P = 3.86 × 10(-8), respectively). We also replicated associations at two previously reported migraine loci in or near TRPM8 and LRP1. This study identifies the first susceptibility loci for migraine without aura, thereby expanding our knowledge of this debilitating neurological disorder.
  Nature Genetics 06/2012; 44(7):777-82. · 35.53 Impact Factor
• Source

  Available from: Thomas Pertel

  Article: IFITM3 restricts the morbidity and mortality associated with influenza.

  Aaron R Everitt, Simon Clare, Thomas Pertel, Sinu P John, Rachael S Wash, Sarah E Smith, Christopher R Chin, Eric M Feeley, Jennifer S Sims, David J Adams, [......], Yali Xue, Vincenza Colonna, Chris Tyler-Smith, Jake Dunning, Stephen B Gordon, Rosalind L Smyth, Peter J Openshaw, Gordon Dougan, Abraham L Brass, Paul Kellam
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  ABSTRACT: The 2009 H1N1 influenza pandemic showed the speed with which a novel respiratory virus can spread and the ability of a generally mild infection to induce severe morbidity and mortality in a subset of the population. Recent in vitro studies show that the interferon-inducible transmembrane (IFITM) protein family members potently restrict the replication of multiple pathogenic viruses. Both the magnitude and breadth of the IFITM proteins' in vitro effects suggest that they are critical for intrinsic resistance to such viruses, including influenza viruses. Using a knockout mouse model, we now test this hypothesis directly and find that IFITM3 is essential for defending the host against influenza A virus in vivo. Mice lacking Ifitm3 display fulminant viral pneumonia when challenged with a normally low-pathogenicity influenza virus, mirroring the destruction inflicted by the highly pathogenic 1918 'Spanish' influenza. Similar increased viral replication is seen in vitro, with protection rescued by the re-introduction of Ifitm3. To test the role of IFITM3 in human influenza virus infection, we assessed the IFITM3 alleles of individuals hospitalized with seasonal or pandemic influenza H1N1/09 viruses. We find that a statistically significant number of hospitalized subjects show enrichment for a minor IFITM3 allele (SNP rs12252-C) that alters a splice acceptor site, and functional assays show the minor CC genotype IFITM3 has reduced influenza virus restriction in vitro. Together these data reveal that the action of a single intrinsic immune effector, IFITM3, profoundly alters the course of influenza virus infection in mouse and humans.
  Nature 03/2012; 484(7395):519-23. · 36.28 Impact Factor
• Article: A Potential Novel Spontaneous Preterm Birth Gene, AR, Identified by Linkage and Association Analysis of X Chromosomal Markers.

  Minna K Karjalainen, Johanna M Huusko, Johanna Ulvila, Jenni Sotkasiira, Aino Luukkonen, Kari Teramo, Jevon Plunkett, Verneri Anttila, Aarno Palotie, Ritva Haataja, Louis J Muglia, Mikko Hallman
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  ABSTRACT: Preterm birth is the major cause of neonatal mortality and morbidity. In many cases, it has severe life-long consequences for the health and neurological development of the newborn child. More than 50% of all preterm births are spontaneous, and currently there is no effective prevention. Several studies suggest that genetic factors play a role in spontaneous preterm birth (SPTB). However, its genetic background is insufficiently characterized. The aim of the present study was to perform a linkage analysis of X chromosomal markers in SPTB in large northern Finnish families with recurrent SPTBs. We found a significant linkage signal (HLOD  = 3.72) on chromosome locus Xq13.1 when the studied phenotype was being born preterm. There were no significant linkage signals when the studied phenotype was giving preterm deliveries. Two functional candidate genes, those encoding the androgen receptor (AR) and the interleukin-2 receptor gamma subunit (IL2RG), located near this locus were analyzed as candidates for SPTB in subsequent case-control association analyses. Nine single-nucleotide polymorphisms (SNPs) within these genes and an AR exon-1 CAG repeat, which was previously demonstrated to be functionally significant, were analyzed in mothers with preterm delivery (n = 272) and their offspring (n = 269), and in mothers with exclusively term deliveries (n = 201) and their offspring (n = 199), all originating from northern Finland. A replication study population consisting of individuals born preterm (n = 111) and term (n = 197) from southern Finland was also analyzed. Long AR CAG repeats (≥26) were overrepresented and short repeats (≤19) underrepresented in individuals born preterm compared to those born at term. Thus, our linkage and association results emphasize the role of the fetal genome in genetic predisposition to SPTB and implicate AR as a potential novel fetal susceptibility gene for SPTB.
  PLoS ONE 01/2012; 7(12):e51378. · 4.09 Impact Factor