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  • 51.
    St Pourcain, Beate
    et al.
    Univ Bristol, Sch Oral & Dent Sci, Bristol BS1 2LY, Avon, England.
    Rodriguez, Alina
    Mittuniversitetet, Fakulteten för humanvetenskap, Avdelningen för psykologi. Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Ctr Environm & Hlth, Dept Epidemiol & Biostat,MRC,Publ Hlth England, London W2 1PG, England.
    Common variation near ​ROBO2 is associated with expressive vocabulary in infancy2014Ingår i: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 5, artikel-id A4831Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Twin studies suggest that expressive vocabulary at ~24 months is modestly heritable. However, the genes influencing this early linguistic phenotype are unknown. Here we conduct a genome-wide screen and follow-up study of expressive vocabulary in toddlers of European descent from up to four studies of the EArly Genetics and Lifecourse Epidemiology consortium, analysing an early (15–18 months, ‘one-word stage’, NTotal=8,889) and a later (24–30 months, ‘two-word stage’,NTotal=10,819) phase of language acquisition. For the early phase, one single-nucleotide polymorphism (rs7642482) at 3p12.3 near ​ROBO2, encoding a conserved axon-binding receptor, reaches the genome-wide significance level (P=1.3 × 10−8) in the combined sample. This association links language-related common genetic variation in the general population to a potential autism susceptibility locus and a linkage region for dyslexia, speech-sound disorder and reading. The contribution of common genetic influences is, although modest, supported by genome-wide complex trait analysis (meta-GCTA h215–18-months=0.13, meta-GCTA h224–30-months=0.14) and in concordance with additional twin analysis (5,733 pairs of European descent,h224-months=0.20).

  • 52. Taal, H. Rob
    et al.
    St Pourcain, Beate
    Thiering, Elisabeth
    Das, Shikta
    Mook-Kanamori, Dennis O.
    Warrington, Nicole M.
    Kaakinen, Marika
    Kreiner-Moller, Eskil
    Bradfield, Jonathan P.
    Freathy, Rachel M.
    Geller, Frank
    Guxens, Monica
    Cousminer, Diana L.
    Kerkhof, Marjan
    Timpson, Nicholas J.
    Ikram, M. Arfan
    Beilin, Lawrence J.
    Bonnelykke, Klaus
    Buxton, Jessica L.
    Charoen, Pimphen
    Chawes, Bo Lund Krogsgaard
    Eriksson, Johan
    Evans, David M.
    Hofman, Albert
    Kemp, John P.
    Kim, Cecilia E.
    Klopp, Norman
    Lahti, Jari
    Lye, Stephen J.
    McMahon, George
    Mentch, Frank D.
    Mueller-Nurasyid, Martina
    O'Reilly, Paul F.
    Prokopenko, Inga
    Rivadeneira, Fernando
    Steegers, Eric A. P.
    Sunyer, Jordi
    Tiesler, Carla
    Yaghootkar, Hanieh
    Breteler, Monique M. B.
    Debette, Stephanie
    Fornage, Myriam
    Gudnason, Vilmundur
    Launer, Lenore J.
    van der Lugt, Aad
    Mosley, Thomas H., Jr.
    Seshadri, Sudha
    Smith, Albert V.
    Vernooij, Meike W.
    Blakemore, Alexandra I. F.
    Chiavacci, Rosetta M.
    Feenstra, Bjarke
    Fernandez-Banet, Julio
    Grant, Struan F. A.
    Hartikainen, Anna-Liisa
    van der Heijden, Albert J.
    Iniguez, Carmen
    Lathrop, Mark
    McArdle, Wendy L.
    Molgaard, Anne
    Newnham, John P.
    Palmer, Lyle J.
    Palotie, Aarno
    Pouta, Annneli
    Ring, Susan M.
    Sovio, Ulla
    Standl, Marie
    Uitterlinden, Andre G.
    Wichmann, H-Erich
    Vissing, Nadja Hawwa
    DeCarli, Charles
    van Duijn, Cornelia M.
    McCarthy, Mark I.
    Koppelman, Gerard H.
    Estivill, Xavier
    Hattersley, Andrew T.
    Melbye, Mads
    Bisgaard, Hans
    Pennell, Craig E.
    Widen, Elisabeth
    Hakonarson, Hakon
    Smith, George Davey
    Heinrich, Joachim
    Jarvelin, Marjo-Riitta
    Jaddoe, Vincent W. V.
    Adair, Linda S.
    Ang, Wei
    Atalay, Mustafa
    van Beijsterveldt, Toos
    Bergen, Nienke
    Benke, Kelly
    Berry, Diane
    Coin, Lachlan
    Davis, Oliver S. P.
    Elliott, Paul
    Flexeder, Claudia
    Frayling, Tim
    Gaillard, Romy
    Groen-Blokhuis, Maria
    Goh, Liang-Kee
    Haworth, Claire M. A.
    Hadley, Dexter
    Hedebrand, Johannes
    Hinney, Anke
    Hirschhorn, Joel N.
    Holloway, John W.
    Holst, Claus
    Hottenga, Jouke Jan
    Horikoshi, Momoko
    Huikari, Ville
    Hypponen, Elina
    Kilpelainen, Tuomas O.
    Kirin, Mirna
    Kowgier, Matthew
    Lakka, Hanna-Maaria
    Lange, Leslie A.
    Lawlor, Debbie A.
    Lehtimaki, Terho
    Lewin, Alex
    Lindgren, Cecilia
    Lindi, Virpi
    Maggi, Reedik
    Marsh, Julie
    Middeldorp, Christel
    Millwood, Iona
    Murray, Jeffrey C.
    Nivard, Michel
    Nohr, Ellen Aagaard
    Ntalla, Ioanna
    Oken, Emily
    Panoutsopoulou, Kalliope
    Pararajasingham, Jennifer
    Rodriguez, Alina
    Mittuniversitetet, Fakulteten för humanvetenskap, Institutionen för samhällsvetenskap.
    Salem, Rany M.
    Sebert, Sylvain
    Siitonen, Niina
    Strachan, David P.
    Teo, Yik-Ying
    Valcarcel, Beatriz
    White, Scott
    Willemsen, Gonneke
    Zeggini, Eleftheria
    Boomsma, Dorret I.
    Cooper, Cyrus
    Gillman, Matthew
    Hocher, Berthold
    Lakka, Timo A.
    Mohlke, Karen L.
    Dedoussis, George V.
    Ong, Ken K.
    Pearson, Ewan R.
    Price, Thomas S.
    Power, Chris
    Raitakari, Olli T.
    Saw, Seang-Mei
    Scherag, Andre
    Simell, Olli
    Sorensen, Thorkild I. A.
    Wilson, James F.
    Schmidt, Reinhold
    Vrooman, Henri A.
    Sigurdsson, Sigurdur
    Ropele, Stefan
    Coker, Laura H.
    Longstreth, W. T., Jr.
    Niessen, Wiro J.
    DeStefano, Anita L.
    Beiser, Alexa
    Zijdenbos, Alex P.
    Struchalin, Maksim
    Jack, Clifford R., Jr.
    Nalls, Mike A.
    Au, Rhoda
    Gudnason, Haukur
    Harris, Tamara B.
    Meeks, William M.
    van Buchem, Mark A.
    Catellier, Diane
    Windham, B. Gwen
    Wolf, Philip A.
    Schmidt, Helena
    Common variants at 12q15 and 12q24 are associated with infant head circumference2012Ingår i: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 44, nr 5, s. 532-538Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    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 x 10(-9)) and rs1042725 on chromosome 12q15 (P = 2.8 x 10(-10)) were robustly associated with head circumference in infancy. Although these loci have previously been associated with adult height(1), their effects on infant head circumference were largely independent of height (P = 3.8 x 10(-7) for rs7980687 and P = 1.3 x 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 x 10(-6)). SNPs correlated to the 17q21 signal have shown genome-wide association with adult intracranial volume(2), Parkinson's disease and other neurodegenerative diseases(3-5), indicating that a common genetic variant in this region might link early brain growth with neurological disease in later life.

  • 53. van der Valk, Ralf J P
    et al.
    Kreiner-Møller, Eskil
    Kooijman, Marjolein N
    Guxens, Mònica
    Stergiakouli, Evangelia
    Sääf, Annika
    Bradfield, Jonathan P
    Geller, Frank
    Hayes, M Geoffrey
    Cousminer, Diana L
    Körner, Antje
    Thiering, Elisabeth
    Curtin, John A
    Myhre, Ronny
    Huikari, Ville
    Joro, Raimo
    Kerkhof, Marjan
    Warrington, Nicole M
    Pitkänen, Niina
    Ntalla, Ioanna
    Horikoshi, Momoko
    Veijola, Riitta
    Freathy, Rachel M
    Teo, Yik-Ying
    Barton, Sheila J
    Evans, David M
    Kemp, John P
    St Pourcain, Beate
    Ring, Susan M
    Davey Smith, George
    Bergström, Anna
    Kull, Inger
    Hakonarson, Hakon
    Mentch, Frank D
    Bisgaard, Hans
    Chawes, Bo
    Stokholm, Jakob
    Waage, Johannes
    Eriksen, Patrick
    Sevelsted, Astrid
    Melbye, Mads
    van Duijn, Cornelia M
    Medina-Gomez, Carolina
    Hofman, Albert
    de Jongste, Johan C
    Taal, H Rob
    Uitterlinden, André G
    Armstrong, Loren L
    Eriksson, Johan
    Palotie, Aarno
    Bustamante, Mariona
    Estivill, Xavier
    Gonzalez, Juan R
    Llop, Sabrina
    Kiess, Wieland
    Mahajan, Anubha
    Flexeder, Claudia
    Tiesler, Carla M T
    Murray, Clare S
    Simpson, Angela
    Magnus, Per
    Sengpiel, Verena
    Hartikainen, Anna-Liisa
    Keinanen-Kiukaanniemi, Sirkka
    Lewin, Alexandra
    Da Silva Couto Alves, Alexessander
    Blakemore, Alexandra I
    Buxton, Jessica L
    Kaakinen, Marika
    Rodriguez, Alina
    Mittuniversitetet, Fakulteten för humanvetenskap, Avdelningen för psykologi.
    Sebert, Sylvain
    Vaarasmaki, Marja
    Lakka, Timo
    Lindi, Virpi
    Gehring, Ulrike
    Postma, Dirkje S
    Ang, Wei
    Newnham, John P
    Lyytikäinen, Leo-Pekka
    Pahkala, Katja
    Raitakari, Olli T
    Panoutsopoulou, Kalliope
    Zeggini, Eleftheria
    Boomsma, Dorret I
    Groen-Blokhuis, Maria
    Ilonen, Jorma
    Franke, Lude
    Hirschhorn, Joel N
    Pers, Tune H
    Liang, Liming
    Huang, Jinyan
    Hocher, Berthold
    Knip, Mikael
    Saw, Seang-Mei
    Holloway, John W
    Melén, Erik
    Grant, Struan F A
    Feenstra, Bjarke
    Lowe, William L
    Widén, Elisabeth
    Sergeyev, Elena
    Grallert, Harald
    Custovic, Adnan
    Jacobsson, Bo
    Jarvelin, Marjo-Riitta
    Atalay, Mustafa
    Koppelman, Gerard H
    Pennell, Craig E
    Niinikoski, Harri
    Dedoussis, George V
    Mccarthy, Mark I
    Frayling, Timothy M
    Sunyer, Jordi
    Timpson, Nicholas J
    Rivadeneira, Fernando
    Bønnelykke, Klaus
    Jaddoe, Vincent W V
    A novel common variant in DCST2 is associated with length in early life and height in adulthood2015Ingår i: Human Molecular Genetics, ISSN 0964-6906, E-ISSN 1460-2083, Vol. 24, nr 4, s. 1155-68, artikel-id ddu510Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Common genetic variants have been identified for adult height, but not much is known about the genetics of skeletal growth in early life. To identify common genetic variants that influence fetal skeletal growth, we meta-analyzed 22 genome-wide association studies (Stage 1; N = 28 459). We identified seven independent top single nucleotide polymorphisms (SNPs) (P < 1 × 10(-6)) for birth length, of which three were novel and four were in or near loci known to be associated with adult height (LCORL, PTCH1, GPR126 and HMGA2). The three novel SNPs were followed-up in nine replication studies (Stage 2; N = 11 995), with rs905938 in DC-STAMP domain containing 2 (DCST2) genome-wide significantly associated with birth length in a joint analysis (Stages 1 + 2; β = 0.046, SE = 0.008, P = 2.46 × 10(-8), explained variance = 0.05%). Rs905938 was also associated with infant length (N = 28 228; P = 5.54 × 10(-4)) and adult height (N = 127 513; P = 1.45 × 10(-5)). DCST2 is a DC-STAMP-like protein family member and DC-STAMP is an osteoclast cell-fusion regulator. Polygenic scores based on 180 SNPs previously associated with human adult stature explained 0.13% of variance in birth length. The same SNPs explained 2.95% of the variance of infant length. Of the 180 known adult height loci, 11 were genome-wide significantly associated with infant length (SF3B4, LCORL, SPAG17, C6orf173, PTCH1, GDF5, ZNFX1, HHIP, ACAN, HLA locus and HMGA2). This study highlights that common variation in DCST2 influences variation in early growth and adult height.

  • 54.
    Young, Susan
    et al.
    Imperial Coll London, London, England; West London Mental Hlth Trust, Broadmoor Hosp, Crowthorne, Berks, England..
    Absoud, Michael
    Guys & St Thomas NHS Fdn Trust, Kings Hlth Partners Acad Hlth Sci Ctr, Evelina London Childrens Hosp, Childrens Neurosci, London, England.
    Blackburn, Carolyn
    Birmingham City Univ, Fac Hlth Educ & Life Sci, Ctr Study Practice & Culture Educ, Birmingham, W Midlands, England.
    Branney, Polly
    Oxford ADHD Ctr, Oxford, England.
    Colley, Bill
    CLC Consultancy, Dunkeld, Scotland.
    Farrag, Emad
    Sussex Partnership NHS Fdn Trust, Children & Young Peoples Serv, Tunbridge Wells, Kent, England.
    Fleisher, Susan
    NOFAS UK, London, England.
    Gregory, Ges
    Cambridge & Peterborough Fdn Trust, Integrated Child Hlth, 80 Thorpe Rd, Peterborough PE3 6AP, Cambs, England.
    Gudjonsson, Gisli H.
    Kings Coll London, Inst Psychiat Psychol & Neurosci, London, England.
    Kim, Keira
    O'Malley, Kieran D.
    Slievemore Clin, Dublin, Ireland; Intellectual Disabil Sect Royal Soc Med, London, England.
    Plant, Moira
    Univ West England, Bristol, Avon, England; Curtin Univ, Natl Drug Res Inst, Perth, WA, Australia.
    Rodriguez, Alina
    Mittuniversitetet, Fakulteten för humanvetenskap, Avdelningen för psykologi. Imperial Coll London, London, England.
    Ozer, Susan
    East & North Hertfordshire NHS Trust, Hatfield, Herts, England.
    Takon, Inyang
    East & North Hertfordshire NHS Trust, Univ Coll Ibadan, Ctr Child & Adolescent Mental Hlth, Hatfield, Herts, England.
    Woodhouse, Emma
    Kings Coll London, Inst Psychiat Psychol & Neurosci, London, England.
    Mukherjee, Raja
    Surrey & Borders Partnership NHS Fdn Trust, FASD Specialist Behav Clin, Oxted, Surrey, England.
    Guidelines for identification and treatment of individuals with attention deficit/hyperactivity disorder and associated fetal alcohol spectrum disorders based upon expert consensus2016Ingår i: BMC Psychiatry, ISSN 1471-244X, E-ISSN 1471-244X, Vol. 16, nr 1, artikel-id 324Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: The association of attention deficit/hyperactivity disorder (ADHD) and fetal alcohol spectrum disorders (FASD) results in a complex constellation of symptoms that complicates the successful diagnosis and treatment of the affected individual. Current literature lacks formal guidelines, randomized control trials, and evidence-based treatment plans for individuals with ADHD and associated FASD. Therefore, a meeting of professional experts was organized with the aim of producing a consensus on identification and treatment guidelines that will aid clinicians in caring for this unique patient population. Methods: Experts from multiple disciplines in the fields of ADHD and FASD convened in London, United Kingdom, for a meeting hosted by the United Kingdom ADHD Partnership (UKAP; www.UKADHD.com) in June 2015. The meeting provided the opportunity to address the complexities of ADHD and FASD from different perspectives and included presentations, discussions, and group work. The attendees worked towards producing a consensus for a unified approach to ADHD and associated FASD. Results: The authors successfully came to consensus and produced recommended guidelines with specific regards to identification and assessment, interventions and treatments, and multiagency liaisons and care management, highlighting that a lifespan approach to treatment needs to be adopted by all involved. Included in the guidelines are: 1) unique 'red flags', which when identified in the ADHD population can lead to an accurate associated FASD diagnosis, 2) a treatment decision tree, and 3) recommendations for multiagency care management. Conclusions: While clinically useful guidelines were achieved, more research is still needed to contribute to the knowledge base about the diagnosis, treatment, and management of those with ADHD and associated FASD.

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