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  • 1. Ikram, M. Arfan
    et al.
    Fornage, Myriam
    Smith, Albert V.
    Seshadri, Sudha
    Schmidt, Reinhold
    Debette, Stephanie
    Vrooman, Henri A.
    Sigurdsson, Sigurdur
    Ropele, Stefan
    Taal, H. Rob
    Mook-Kanamori, Dennis O.
    Coker, Laura H.
    Longstreth, W. T., Jr.
    Niessen, Wiro J.
    DeStefano, Anita L.
    Beiser, Alexa
    Zijdenbos, Alex P.
    Struchalin, Maksim
    Jack, Clifford R., Jr.
    Rivadeneira, Fernando
    Uitterlinden, Andre G.
    Knopman, David S.
    Hartikainen, Anna-Liisa
    Pennell, Craig E.
    Thiering, Elisabeth
    Steegers, Eric A. P.
    Hakonarson, Hakon
    Heinrich, Joachim
    Palmer, Lyle J.
    Jarvelin, Marjo-Riitta
    McCarthy, Mark I.
    Grant, Struan F. A.
    St Pourcain, Beate
    Timpson, Nicholas J.
    Smith, George Davey
    Sovio, Ulla
    Nalls, Mike A.
    Au, Rhoda
    Hofman, Albert
    Gudnason, Haukur
    van der Lugt, Aad
    Harris, Tamara B.
    Meeks, William M.
    Vernooij, Meike W.
    van Buchem, Mark A.
    Catellier, Diane
    Jaddoe, Vincent W. V.
    Gudnason, Vilmundur
    Windham, B. Gwen
    Wolf, Philip A.
    van Duijn, Cornelia M.
    Mosley, Thomas H., Jr.
    Schmidt, Helena
    Launer, Lenore J.
    Breteler, Monique M. B.
    DeCarli, Charles
    Adair, Linda S.
    Ang, Wei
    Atalay, Mustafa
    vanBeijsterveldt, 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
    Mid Sweden University, Faculty of Human Sciences, Department of Social Sciences.
    Salem, Rany M.
    Sebert, Sylvain
    Siitonen, Niina
    Strachan, David P.
    Teo, Yik-Ying
    Valcarcel, Beatriz
    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.
    Common variants at 6q22 and 17q21 are associated with intracranial volume2012In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 44, no 5, p. 539-544Article in journal (Refereed)
    Abstract [en]

    During aging, intracranial volume remains unchanged and represents maximally attained brain size, while various interacting biological phenomena lead to brain volume loss. Consequently, intracranial volume and brain volume in late life reflect different genetic influences. Our genome-wide association study (GWAS) in 8,175 community-dwelling elderly persons did not reveal any associations at genome-wide significance (P < 5 x 10(-8)) for brain volume. In contrast, intracranial volume was significantly associated with two loci: rs4273712 (P = 3.4 x 10(-11)), a known height-associated locus on chromosome 6q22, and rs9915547 (P = 1.5 x 10(-12)), localized to the inversion on chromosome 17q21. We replicated the associations of these loci with intracranial volume in a separate sample of 1,752 elderly persons (P = 1.1 x 10(-3) for 6q22 and 1.2 x 10(-3) for 17q21). Furthermore, we also found suggestive associations of the 17q21 locus with head circumference in 10,768 children (mean age of 14.5 months). Our data identify two loci associated with head size, with the inversion at 17q21 also likely to be involved in attaining maximal brain size.

  • 2.
    Khan, Anokhi Ali
    et al.
    Univ London Imperial Coll Sci Technol & Med, Ctr Environm & Hlth, Hlth Protect Agcy, Med Res Council,Dept Epidemiol & Biostat, London, England.
    Rodriguez, Alina
    Mid Sweden University, Faculty of Human Sciences, Department of Social Sciences.
    Sebert, Sylvain
    Univ London Imperial Coll Sci Technol & Med, Ctr Environm & Hlth, Hlth Protect Agcy, Med Res Council,Dept Epidemiol & Biostat, London, England.
    Kaakinen, Marika
    Univ Oulu, Inst Hlth Sci, Oulu, Finland.
    Cauchi, Stephane
    Univ Lille 2, Inst Pasteur, Inst Biol Lille, Ctr Natl Rech Sci,Unites Mixte Rech 8199, F-59800 Lille, France.
    Froguel, Philippe
    Univ Lille 2, Inst Pasteur, Inst Biol Lille, Ctr Natl Rech Sci,Unites Mixte Rech 8199, F-59800 Lille, France.
    Hartikainen, Anna-Liisa
    Univ Oulu, Dept Clin Sci Obstet & Gynecol, Oulu, Finland.
    Pouta, Anneli
    Natl Inst Hlth & Welf, Oulu, Finland.
    Jarvelin, Marjo-Riitta
    Univ London Imperial Coll Sci Technol & Med, Ctr Environm & Hlth, Hlth Protect Agcy, Med Res Council,Dept Epidemiol & Biostat, London, England.
    The Interplay of Variants Near LEKR and CCNL1 and Social Stress in Relation to Birth Size2012In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, no 6, p. Art. no. e38216-Article in journal (Refereed)
    Abstract [en]

    Background: We previously identified via a genome wide association study variants near LEKR and CCNL1 and in the ADCY5 genes lead to lower birthweight. Here, we study the impact of these variants and social stress during pregnancy, defined as social adversity and neighborhood disparity, on infant birth size. We aimed to determine whether the addition of genetic variance magnified the observed associations. Methodology/Principal Findings: We analyzed data from the Northern Finland Birth Cohort 1986 (n = 5369). Social adversity was defined by young maternal age (<20 years), low maternal education (<11 years), and/or single marital status. Neighborhood social disparity was assessed by discrepancy between neighborhoods relative to personal socio-economic status. These variables are indicative of social and socioeconomic stress, but also of biological risk. The adjusted multiple regression analysis showed smaller birth size in both infants of mothers who experienced social adversity (birthweight by -40.4 g, 95% CI -61.4, -19.5; birth length -0.14 cm, 95% CI -0.23, -0.05; head circumference -0.09 cm 95% CI -0.15, -0.02) and neighborhood disparity (birthweight -28.8 g, 95% CI -47.7, -10.0; birth length -0.12 cm, 95% CI -0.20, -0.05). The birthweight-lowering risk allele (SNP rs900400 near LEKR and CCNL1) magnified this association in an additive manner. However, likely due to sample size restriction, this association was not significant for the SNP rs9883204 in ADCY5. Birth size difference due to social stress was greater in the presence of birthweight-lowering alleles. Conclusions/Significance: Social adversity, neighborhood disparity, and genetic variants have independent associations with infant birth size in the mutually adjusted analyses. If the newborn carried a risk allele rs900400 near LEKR/CCNL1, the impact of stress on birth size was stronger. These observations give support to the hypothesis that individuals with genetic or other biological risk are more vulnerable to environmental influences. Our study indicates the need for further research to understand the mechanisms by which genes impact individual vulnerability to environmental insults.

  • 3. 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
    Mid Sweden University, Faculty of Human Sciences, Department of Social Sciences.
    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 circumference2012In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 44, no 5, p. 532-538Article in journal (Refereed)
    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.

  • 4.
    Temrin, H.
    et al.
    Stockholm Univ, Dept Zool, SE-10691 Stockholm, Sweden .
    Nordlund, J.
    Stockholm Univ, Dept Zool, SE-10691 Stockholm, Sweden .
    Rying, Mikael
    Mid Sweden University, Faculty of Human Sciences, Department of Health Sciences.
    Tullberg, B. S.
    Stockholm Univ, Dept Zool, SE-10691 Stockholm, Sweden .
    Is the higher rate of parental child homicide in stepfamilies an effect of non-genetic relatedness?2011In: Current Zoology, ISSN 1674-5507, Vol. 57, no 3, p. 253-259Article in journal (Refereed)
    Abstract [en]

    In an evolutionary perspective individuals are expected to vary the degree of parental love and care in relation to the fitness value that a child represents. Hence, stepparents are expected to show less solicitude than genetically related parents, and this lack of genetic relatedness has been used to explain the higher frequencies of child abuse and homicide found in stepfamilies. However, other factors than non-genetic relatedness may cause this over-representation in stepfamilies. Here we use a 45-year data set of parental child homicides in Sweden to test two hypotheses related to the higher incidence in stepfamilies: 1) adults in different types of family differ in their general disposition to use violence, and 2) parents are more likely to kill stepchildren than genetically related children. Of the 152 perpetrators in biparental families there was an overrepresentation of perpetrators in stepfamilies (n=27) compared with the general population. We found support for the first hypothesis in that both general and violent crime rates were higher in stepfamilies, both in the general population and among perpetrators of child homicide. However, we found no support for the second hypothesis because of the 27 perpetrators in stepfamilies the perpetrator killed a genetically related child in 13 cases, a stepchild in 13 cases and both types of children in one case. Moreover, out of the 12 families where the perpetrator lived with both stepchildren and genetic children, there was no bias towards killing stepchildren. Thus, we found no evidence for an effect of non-genetic relatedness per se. 

  • 5. 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
    Mid Sweden University, Faculty of Human Sciences, Department of Psychology.
    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 adulthood2015In: Human Molecular Genetics, ISSN 0964-6906, E-ISSN 1460-2083, Vol. 24, no 4, p. 1155-68, article id ddu510Article in journal (Refereed)
    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.

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