Title | Directional dominance on stature and cognition in diverse human populations. |
Publication Type | Journal Article |
Year of Publication | 2015 |
Authors | Joshi, PK, Esko, T, Mattsson, H, Eklund, N, Gandin, I, Nutile, T, Jackson, AU, Schurmann, C, Smith, AVernon, Zhang, W, Okada, Y, Stančáková, A, Faul, J, Zhao, W, Bartz, TM, Concas, MPina, Franceschini, N, Enroth, S, Vitart, V, Trompet, S, Guo, X, Chasman, DI, O'Connell, J, Corre, T, Nongmaithem, SS, Chen, Y, Mangino, M, Ruggiero, D, Traglia, M, Farmaki, A-E, Kacprowski, T, Bjonnes, A, van der Spek, A, Wu, Y, Giri, AK, Yanek, LR, Wang, L, Hofer, E, Rietveld, CA, McLeod, O, Cornelis, MC, Pattaro, C, Verweij, N, Baumbach, C, Abdellaoui, A, Warren, HR, Vuckovic, D, Mei, H, Bouchard, C, Perry, JRB, Cappellani, S, Mirza, SS, Benton, MC, Broeckel, U, Medland, SE, Lind, PA, Malerba, G, Drong, AW, Yengo, L, Bielak, LF, Zhi, D, van der Most, PJ, Shriner, D, Mägi, R, Hemani, G, Karaderi, T, Wang, Z, Liu, T, Demuth, I, Zhao, JHua, Meng, W, Lataniotis, L, van der Laan, SW, Bradfield, JP, Wood, AR, Bonnefond, A, Ahluwalia, TS, Hall, LM, Salvi, E, Yazar, S, Carstensen, L, de Haan, HG, Abney, M, Afzal, U, Allison, MA, Amin, N, Asselbergs, FW, Bakker, SJL, R Barr, G, Baumeister, SE, Benjamin, DJ, Bergmann, S, Boerwinkle, E, Bottinger, EP, Campbell, A, Chakravarti, A, Chan, Y, Chanock, SJ, Chen, C, Chen, Y-DI, Collins, FS, Connell, J, Correa, A, L Cupples, A, Davies, G, Dörr, M, Ehret, GB, Ellis, SB, Feenstra, B, Feitosa, MF, Ford, I, Fox, CS, Frayling, TM, Friedrich, N, Geller, F, Scotland, G, Gillham-Nasenya, I, Gottesman, O, Graff, M, Grodstein, F, Gu, C, Haley, C, Hammond, CJ, Harris, SE, Harris, TB, Hastie, ND, Heard-Costa, NL, Heikkilä, K, Hocking, LJ, Homuth, G, Hottenga, J-J, Huang, J, Huffman, JE, Hysi, PG, Ikram, MArfan, Ingelsson, E, Joensuu, A, Johansson, Å, Jousilahti, P, J Jukema, W, Kähönen, M, Kamatani, Y, Kanoni, S, Kerr, SM, Khan, NM, Koellinger, PD, Koistinen, HA, Kooner, MK, Kubo, M, Kuusisto, J, Lahti, J, Launer, LJ, Lea, RA, Lehne, B, Lehtimäki, T, Liewald, DC, Lind, L, Loh, M, Lokki, M-L, London, SJ, Loomis, SJ, Loukola, A, Lu, Y, Lumley, T, Lundqvist, A, Männistö, S, Marques-Vidal, P, Masciullo, C, Matchan, A, Mathias, RA, Matsuda, K, Meigs, JB, Meisinger, C, Meitinger, T, Menni, C, Mentch, FD, Mihailov, E, Milani, L, Montasser, ME, Montgomery, GW, Morrison, AC, Myers, RH, Nadukuru, R, Navarro, P, Nelis, M, Nieminen, MS, Nolte, IM, O'Connor, GT, Ogunniyi, A, Padmanabhan, S, Palmas, WR, Pankow, JS, Patarcic, I, Pavani, F, Peyser, PA, Pietilainen, K, Poulter, N, Prokopenko, I, Ralhan, S, Redmond, P, Rich, SS, Rissanen, H, Robino, A, Rose, LM, Rose, R, Sala, CFelicita, Salako, B, Salomaa, V, Sarin, A-P, Saxena, R, Schmidt, H, Scott, LJ, Scott, WR, Sennblad, B, Seshadri, S, Sever, P, Shrestha, S, Smith, BH, Smith, JA, Soranzo, N, Sotoodehnia, N, Southam, L, Stanton, AV, Stathopoulou, MG, Strauch, K, Strawbridge, RJ, Suderman, MJ, Tandon, N, Tang, S-T, Taylor, KD, Tayo, BO, Töglhofer, AMaria, Tomaszewski, M, Tšernikova, N, Tuomilehto, J, Uitterlinden, AG, Vaidya, D, Vlieg, Avan Hylcka, van Setten, J, Vasankari, T, Vedantam, S, Vlachopoulou, E, Vozzi, D, Vuoksimaa, E, Waldenberger, M, Ware, EB, Wentworth-Shields, W, Whitfield, JB, Wild, S, Willemsen, G, Yajnik, CS, Yao, J, Zaza, G, Zhu, X, Salem, RM, Melbye, M, Bisgaard, H, Samani, NJ, Cusi, D, Mackey, DA, Cooper, RS, Froguel, P, Pasterkamp, G, Grant, SFA, Hakonarson, H, Ferrucci, L, Scott, RA, Morris, AD, Palmer, CNA, Dedoussis, G, Deloukas, P, Bertram, L, Lindenberger, U, Berndt, SI, Lindgren, CM, Timpson, NJ, Tönjes, A, Munroe, PB, Sørensen, TIA, Rotimi, CN, Arnett, DK, Oldehinkel, AJ, Kardia, SLR, Balkau, B, Gambaro, G, Morris, AP, Eriksson, JG, Wright, MJ, Martin, NG, Hunt, SC, Starr, JM, Deary, IJ, Griffiths, LR, Tiemeier, H, Pirastu, N, Kaprio, J, Wareham, NJ, Pérusse, L, Wilson, JG, Girotto, GG, Caulfield, MJ, Raitakari, OT, Boomsma, DI, Gieger, C, van der Harst, P, Hicks, AA, Kraft, P, Sinisalo, J, Knekt, P, Johannesson, M, Magnusson, PKE, Hamsten, A, Schmidt, R, Borecki, IB, Vartiainen, E, Becker, DM, Bharadwaj, D, Mohlke, KL, Boehnke, M, van Duijn, CM, Sanghera, DK, Teumer, A, Zeggini, E, Metspalu, A, Gasparini, PP, Ulivi, S, Ober, C, Toniolo, D, Rudan, I, Porteous, DJ, Ciullo, M, Spector, T, Hayward, C, Dupuis, J, Loos, RJF, Wright, AF, Chandak, GR, Vollenweider, P, Shuldiner, AR, Ridker, PM, Rotter, JI, Sattar, N, Gyllensten, U, North, KE, Pirastu, M, Psaty, BM, Weir, DR, Laakso, M, Gudnason, V, Takahashi, A, Chambers, JC, Kooner, JS, Strachan, DP, Campbell, H, Hirschhron, JN, Perola, M, Polasek, O, Wilson, JF |
Corporate Authors | BioBank Japan Project |
Journal | Nature |
Volume | 523 |
Issue | 7561 |
Pagination | 459-62 |
Date Published | 2015 Jul 23 |
ISSN Number | 1476-4687 |
Keywords | Biological Evolution, Blood pressure, Body Height, Cholesterol, Cognitive Ability, Cohort Studies, Education, Female, Forced Expiratory Volume, Genome, Homozygote, Humans, Lung Volume Measurements, Male, Phenotype |
Abstract | Homozygosity has long been associated with rare, often devastating, Mendelian disorders, and Darwin was one of the first to recognize that inbreeding reduces evolutionary fitness. However, the effect of the more distant parental relatedness that is common in modern human populations is less well understood. Genomic data now allow us to investigate the effects of homozygosity on traits of public health importance by observing contiguous homozygous segments (runs of homozygosity), which are inferred to be homozygous along their complete length. Given the low levels of genome-wide homozygosity prevalent in most human populations, information is required on very large numbers of people to provide sufficient power. Here we use runs of homozygosity to study 16 health-related quantitative traits in 354,224 individuals from 102 cohorts, and find statistically significant associations between summed runs of homozygosity and four complex traits: height, forced expiratory lung volume in one second, general cognitive ability and educational attainment (P < 1 × 10(-300), 2.1 × 10(-6), 2.5 × 10(-10) and 1.8 × 10(-10), respectively). In each case, increased homozygosity was associated with decreased trait value, equivalent to the offspring of first cousins being 1.2 cm shorter and having 10 months' less education. Similar effect sizes were found across four continental groups and populations with different degrees of genome-wide homozygosity, providing evidence that homozygosity, rather than confounding, directly contributes to phenotypic variance. Contrary to earlier reports in substantially smaller samples, no evidence was seen of an influence of genome-wide homozygosity on blood pressure and low density lipoprotein cholesterol, or ten other cardio-metabolic traits. Since directional dominance is predicted for traits under directional evolutionary selection, this study provides evidence that increased stature and cognitive function have been positively selected in human evolution, whereas many important risk factors for late-onset complex diseases may not have been. |
DOI | 10.1038/nature14618 |
User Guide Notes | |
Alternate Journal | Nature |
Citation Key | 8884 |
PubMed ID | 26131930 |
PubMed Central ID | PMC4516141 |
Grant List | U01 AG009740 / AG / NIA NIH HHS / United States R01 HL085197 / HL / NHLBI NIH HHS / United States MR/K006584/1 / MRC_ / Medical Research Council / United Kingdom ETM/55 / CSO_ / Chief Scientist Office / United Kingdom R01 DK093757 / DK / NIDDK NIH HHS / United States R01 DK078616 / DK / NIDDK NIH HHS / United States 105022 / WT_ / Wellcome Trust / United Kingdom CZB/4/505 / CSO_ / Chief Scientist Office / United Kingdom CZB/4/710 / CSO_ / Chief Scientist Office / United Kingdom G9521010 / MRC_ / Medical Research Council / United Kingdom G1001799 / MRC_ / Medical Research Council / United Kingdom 072856 / WT_ / Wellcome Trust / United Kingdom CZD/16/6/2 / CSO_ / Chief Scientist Office / United Kingdom R01 NS017950 / NS / NINDS NIH HHS / United States R01 HL104135 / HL / NHLBI NIH HHS / United States CZD/16/6 / CSO_ / Chief Scientist Office / United Kingdom BARCVBRU-2012-1 / DH_ / Department of Health / United Kingdom MR/K002414/1 / MRC_ / Medical Research Council / United Kingdom R01 HL091357 / HL / NHLBI NIH HHS / United States MC_UU_12013/3 / MRC_ / Medical Research Council / United Kingdom MC_U127561128 / MRC_ / Medical Research Council / United Kingdom G0700931 / MRC_ / Medical Research Council / United Kingdom R03 DC013373 / DC / NIDCD NIH HHS / United States CZB/4/276 / CSO_ / Chief Scientist Office / United Kingdom R01 HL077612 / HL / NHLBI NIH HHS / United States R01 DK072193 / DK / NIDDK NIH HHS / United States 084723 / WT_ / Wellcome Trust / United Kingdom R01 DK075787 / DK / NIDDK NIH HHS / United States UL1 TR000124 / TR / NCATS NIH HHS / United States MR/K026992/1 / MRC_ / Medical Research Council / United Kingdom G0601966 / MRC_ / Medical Research Council / United Kingdom MC_UU_12015/1 / MRC_ / Medical Research Council / United Kingdom SAG09977 / BB_ / Biotechnology and Biological Sciences Research Council / United Kingdom 250157 / ERC_ / European Research Council / International 072960 / WT_ / Wellcome Trust / United Kingdom MC_U106179471 / MRC_ / Medical Research Council / United Kingdom MR/N01104X/1 / MRC_ / Medical Research Council / United Kingdom P30 DK063491 / DK / NIDDK NIH HHS / United States U01 HL072524 / HL / NHLBI NIH HHS / United States MC_UU_12015/2 / MRC_ / Medical Research Council / United Kingdom 098051 / WT_ / Wellcome Trust / United Kingdom R01 AG008122 / AG / NIA NIH HHS / United States 079771 / WT_ / Wellcome Trust / United Kingdom MC_PC_15018 / MRC_ / Medical Research Council / United Kingdom P20 MD006899 / MD / NIMHD NIH HHS / United States R01 HD056465 / HD / NICHD NIH HHS / United States MC_U106179472 / MRC_ / Medical Research Council / United Kingdom R01 AG033193 / AG / NIA NIH HHS / United States MC_PC_U127592696 / MRC_ / Medical Research Council / United Kingdom 068545 / WT_ / Wellcome Trust / United Kingdom MC_UU_12013/1 / MRC_ / Medical Research Council / United Kingdom G0701863 / MRC_ / Medical Research Council / United Kingdom CZD/16/6/4 / CSO_ / Chief Scientist Office / United Kingdom MC_PC_U127561128 / MRC_ / Medical Research Council / United Kingdom UM1 CA182913 / CA / NCI NIH HHS / United States 280559 / ERC_ / European Research Council / International U01 DK078616 / DK / NIDDK NIH HHS / United States U01 DK062370 / DK / NIDDK NIH HHS / United States P30 AG017265 / AG / NIA NIH HHS / United States R01 DK089256 / DK / NIDDK NIH HHS / United States RG/2001004/12869 / BHF_ / British Heart Foundation / United Kingdom P30 DK020572 / DK / NIDDK NIH HHS / United States G0700704 / MRC_ / Medical Research Council / United Kingdom 323195 / ERC_ / European Research Council / International P30 AG010129 / AG / NIA NIH HHS / United States CZD/16/6/3 / CSO_ / Chief Scientist Office / United Kingdom BB/F019394/1 / BB_ / Biotechnology and Biological Sciences Research Council / United Kingdom 099194 / WT_ / Wellcome Trust / United Kingdom R01 HL117078 / HL / NHLBI NIH HHS / United States SRF/01/010 / DH_ / Department of Health / United Kingdom R01 HG002899 / HG / NHGRI NIH HHS / United States R01 HL055673 / HL / NHLBI NIH HHS / United States RP-PG-0407-10371 / DH_ / Department of Health / United Kingdom G9815508 / MRC_ / Medical Research Council / United Kingdom U01 AG049505 / AG / NIA NIH HHS / United States |