New loci associated with birth weight identify genetic links between intrauterine growth and adult height and metabolism.
Horikoshi M., Yaghootkar H., Mook-Kanamori DO., Sovio U., Taal HR., Hennig BJ., Bradfield JP., St Pourcain B., Evans DM., Charoen P., Kaakinen M., Cousminer DL., Lehtimäki T., Kreiner-Møller E., Warrington NM., Bustamante M., Feenstra B., Berry DJ., Thiering E., Pfab T., Barton SJ., Shields BM., Kerkhof M., van Leeuwen EM., Fulford AJ., Kutalik Z., Zhao JH., den Hoed M., Mahajan A., Lindi V., Goh L-K., Hottenga J-J., Wu Y., Raitakari OT., Harder MN., Meirhaeghe A., Ntalla I., Salem RM., Jameson KA., Zhou K., Monies DM., Lagou V., Kirin M., Heikkinen J., Adair LS., Alkuraya FS., Al-Odaib A., Amouyel P., Andersson EA., Bennett AJ., Blakemore AIF., Buxton JL., Dallongeville J., Das S., de Geus EJC., Estivill X., Flexeder C., Froguel P., Geller F., Godfrey KM., Gottrand F., Groves CJ., Hansen T., Hirschhorn JN., Hofman A., Hollegaard MV., Hougaard DM., Hyppönen E., Inskip HM., Isaacs A., Jørgensen T., Kanaka-Gantenbein C., Kemp JP., Kiess W., Kilpeläinen TO., Klopp N., Knight BA., Kuzawa CW., McMahon G., Newnham JP., Niinikoski H., Oostra BA., Pedersen L., Postma DS., Ring SM., Rivadeneira F., Robertson NR., Sebert S., Simell O., Slowinski T., Tiesler CMT., Tönjes A., Vaag A., Viikari JS., Vink JM., Vissing NH., Wareham NJ., Willemsen G., Witte DR., Zhang H., Zhao J., Meta-Analyses of Glucose- and Insulin-related traits Consortium (MAGIC) None., Wilson JF., Stumvoll M., Prentice AM., Meyer BF., Pearson ER., Boreham CAG., Cooper C., Gillman MW., Dedoussis GV., Moreno LA., Pedersen O., Saarinen M., Mohlke KL., Boomsma DI., Saw S-M., Lakka TA., Körner A., Loos RJF., Ong KK., Vollenweider P., van Duijn CM., Koppelman GH., Hattersley AT., Holloway JW., Hocher B., Heinrich J., Power C., Melbye M., Guxens M., Pennell CE., Bønnelykke K., Bisgaard H., Eriksson JG., Widén E., Hakonarson H., Uitterlinden AG., Pouta A., Lawlor DA., Smith GD., Frayling TM., McCarthy MI., Grant SFA., Jaddoe VWV., Jarvelin M-R., Timpson NJ., Prokopenko I., Freathy RM., Early Growth Genetics (EGG) Consortium None.
Birth weight within the normal range is associated with a variety of adult-onset diseases, but the mechanisms behind these associations are poorly understood. Previous genome-wide association studies of birth weight identified a variant in the ADCY5 gene associated both with birth weight and type 2 diabetes and a second variant, near CCNL1, with no obvious link to adult traits. In an expanded genome-wide association meta-analysis and follow-up study of birth weight (of up to 69,308 individuals of European descent from 43 studies), we have now extended the number of loci associated at genome-wide significance to 7, accounting for a similar proportion of variance as maternal smoking. Five of the loci are known to be associated with other phenotypes: ADCY5 and CDKAL1 with type 2 diabetes, ADRB1 with adult blood pressure and HMGA2 and LCORL with adult height. Our findings highlight genetic links between fetal growth and postnatal growth and metabolism.