Directional dominance on stature and cognition in diverse human populations.

TitleDirectional dominance on stature and cognition in diverse human populations.
Publication TypeJournal Article
Year of Publication2015
AuthorsJoshi, PK, Esko, T, Mattsson, H, Eklund, N, Gandin, I, Nutile, T, Jackson, AU, Schurmann, C, Smith, AVernon, Zhang, W, Okada, Y, Stančáková, A, Faul, JD, Zhao, W, Bartz, TM, Concas, MPina, Franceschini, N, Enroth, S, Vitart, V, Trompet, S, Guo, X, Chasman, DI, O'Connel, JR, 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, M, 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, A, 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-DIda, Collins, FS, Connell, J, Correa, A, L Cupples, A, Davies, G, Dörr, M, Ehret, G, 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, M Ikram, A, Ingelsson, E, Joensuu, A, Johansson, Å, Jousilahti, P, J Jukema, W, Kähönen, M, Kamatani, Y, Kanoni, S, Kerr, SM, Khan, NM, Koellinger, P, Koistinen, HA, Kooner, MK, Kubo, M, Kuusisto, J, Lahti, J, Launer, LJ, Lea, RA, Lehne, B, Lehtimäki, T, Liewald, DC, Lars Lind, 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, A, Myers, RH, Nadukuru, R, Navarro, P, Nelis, M, Nieminen, MS, Nolte, IM, O'Connor, GT, Ogunniyi, A, Padmanabhan, S, Palmas, W, 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, C, 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, K, Tayo, B, 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, N, 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, NN, Kaprio, J, Wareham, NJ, Pérusse, L, Wilson, JG, Girotto, G, 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, P, Ulivi, S, Ober, C, Toniolo, D, Rudan, I, Porteous, D, Ciullo, M, Spector, TD, 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, Hirschhorn, J, Perola, M, Polasek, O, Wilson, JF
Corporate AuthorsBioBank Japan Project
JournalNature
Volume523
Issue7561
Pagination459-62
Date Published2015 Jul 23
ISSN Number1476-4687
KeywordsBiological 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.

DOI10.1038/nature14618
User Guide Notes

http://www.ncbi.nlm.nih.gov/pubmed/26131930?dopt=Abstract

Alternate JournalNature
Citation Key8884
PubMed ID26131930
PubMed Central IDPMC4516141
Grant ListETM/55 / / Chief Scientist Office / United Kingdom
R01 DK078616 / DK / NIDDK NIH HHS / United States
105022 / / Wellcome Trust / United Kingdom
CZB/4/505 / / Chief Scientist Office / United Kingdom
CZB/4/710 / / Chief Scientist Office / United Kingdom
G9521010 / / Medical Research Council / United Kingdom
G1001799 / / Medical Research Council / United Kingdom
072856 / / Wellcome Trust / United Kingdom
CZD/16/6/2 / / Chief Scientist Office / United Kingdom
CZD/16/6 / / Chief Scientist Office / United Kingdom
BARCVBRU-2012-1 / / Department of Health / United Kingdom
MC_UU_12013/3 / / Medical Research Council / United Kingdom
MC_U127561128 / / Medical Research Council / United Kingdom
G0700931 / / Medical Research Council / United Kingdom
R03 DC013373 / DC / NIDCD NIH HHS / United States
CZB/4/276 / / Chief Scientist Office / United Kingdom
R01 HL077612 / HL / NHLBI NIH HHS / United States
R01 DK072193 / DK / NIDDK NIH HHS / United States
084723 / / Wellcome Trust / United Kingdom
/ / Medical Research Council / United Kingdom
R01 DK075787 / DK / NIDDK NIH HHS / United States
UL1 TR000124 / TR / NCATS NIH HHS / United States
MR/K026992/1 / / Medical Research Council / United Kingdom
G0601966 / / Medical Research Council / United Kingdom
MC_UU_12015/1 / / Medical Research Council / United Kingdom
SAG09977 / / Biotechnology and Biological Sciences Research Council / United Kingdom
250157 / / European Research Council / International
072960 / / Wellcome Trust / United Kingdom
MC_U106179471 / / Medical Research Council / United Kingdom
MR/N01104X/1 / / Medical Research Council / United Kingdom
P30 DK063491 / DK / NIDDK NIH HHS / United States
MC_UU_12015/2 / / Medical Research Council / United Kingdom
098051 / / Wellcome Trust / United Kingdom
079771 / / Wellcome Trust / United Kingdom
P20 MD006899 / MD / NIMHD NIH HHS / United States
R01 HD056465 / HD / NICHD NIH HHS / United States
MC_U106179472 / / Medical Research Council / United Kingdom
R01 AG033193 / AG / NIA NIH HHS / United States
MC_PC_U127592696 / / Medical Research Council / United Kingdom
MC_UU_12013/1 / / Medical Research Council / United Kingdom
G0701863 / / Medical Research Council / United Kingdom
068545 / / Wellcome Trust / United Kingdom
CZD/16/6/4 / / Chief Scientist Office / United Kingdom
MC_PC_U127561128 / / Medical Research Council / United Kingdom
UM1 CA182913 / CA / NCI NIH HHS / United States
280559 / / European Research Council / International
U01 DK078616 / DK / NIDDK NIH HHS / United States
U01 DK062370 / DK / NIDDK NIH HHS / United States
R01 DK089256 / DK / NIDDK NIH HHS / United States
RG/2001004/12869 / / British Heart Foundation / United Kingdom
MR/K006584/1 / / Medical Research Council / United Kingdom
P30 DK020572 / DK / NIDDK NIH HHS / United States
G0700704 / / Medical Research Council / United Kingdom
323195 / / European Research Council / International
CZD/16/6/3 / / Chief Scientist Office / United Kingdom
BB/F019394/1 / / Biotechnology and Biological Sciences Research Council / United Kingdom
099194 / / Wellcome Trust / United Kingdom
R01 HL117078 / HL / NHLBI NIH HHS / United States
SRF/01/010 / / Department of Health / United Kingdom
RP-PG-0407-10371 / / Department of Health / United Kingdom
G9815508 / / Medical Research Council / United Kingdom
U01 AG049505 / AG / NIA NIH HHS / United States