Genome-wide scan of 29,141 African Americans finds no evidence of directional selection since admixture.

The extent of recent selection in admixed populations is currently an unresolved question. We scanned the genomes of 29,141 African Americans and failed to find any genome-wide-significant deviations in local ancestry, indicating no evidence of selection influencing ancestry after admixture. A recent analysis of data from 1,890 African Americans reported that there was evidence of selection in African Americans after their ancestors left Africa, both before and after admixture. Selection after admixture was reported on the basis of deviations in local ancestry, and selection before admixture was reported on the basis of allele-frequency differences between African Americans and African populations. The local-ancestry deviations reported by the previous study did not replicate in our very large sample, and we show that such deviations were expected purely by chance, given the number of hypotheses tested. We further show that the previous study's conclusion of selection in African Americans before admixture is also subject to doubt. This is because the FST statistics they used were inflated and because true signals of unusual allele-frequency differences between African Americans and African populations would be best explained by selection that occurred in Africa prior to migration to the Americas.

Melinda C Aldrich | Gaurav Bhatia | David Reich | John S Witte | Christopher A Haiman | Brian E Henderson | Christine B Ambrosone | Stephen J Chanock | Wei Zheng | Nick Patterson | Regina G Ziegler | Graham Casey | Emma Larkin | John K Wiencke | Krista A. Zanetti | Alkes L Price | Leslie Bernstein | Elizabeth M Gillanders | Xifeng Wu | William J Blot | Sonja I Berndt | Lisa B Signorello | J. Witte | D. Reich | N. Patterson | R. Millikan | E. Gillanders | A. Price | S. Chanock | M. Spitz | R. Kittles | B. Henderson | C. Haiman | S. Ingles | E. John | Xifeng Wu | C. Harris | C. Amos | Arti Tandon | R. Ziegler | M. Tucker | W. Isaacs | W. Zheng | L. Signorello | W. Blot | S. Berndt | G. Casey | L. Bernstein | W. R. Diver | S. Gapstur | M. Aldrich | G. Bhatia | S. Deming | P. De Jager | S. Strom | M. Press | J. Wiencke | C. Ambrosone | A. Schwartz | L. McNeill | E. Larkin | E. Bandera | C. Bock | N. Caporaso | A. Murphy | C. Neslund-Dudas | S. Nyante | J. Rodriguez-Gil | B. Rybicki | Y. Yamamura | K. Zanetti | Cathryn H Bock | Neil Caporaso | Susan M Gapstur | W Ryan Diver | Arti Tandon | Rick A Kittles | Curtis C Harris | Elisa V Bandera | Margaret A Tucker | Esther M John | Michael F Press | Ann G Schwartz | William Isaacs | Lorna H McNeill | Christopher Amos | Krista A Zanetti | Sandra L. Deming | Lorna H. McNeill | Adam Murphy | Christine Neslund-Dudas | Sarah Nyante | Jorge L. Rodriguez-Gil | Margaret Spitz | Yuko Yamamura | Sandra L Deming | Sue A Ingles | Phillip L De Jager | Robert C Millikan | Jorge L Rodriguez-Gil | Benjamin A Rybicki | Sara S Strom | Adam B. Murphy | W. Diver | R. Ziegler | David Reich | Esther M. John | Alkes L. Price | B. Henderson | Yuko Yamamura | Phillip L. De Jager

[1]  R. Nielsen,et al.  Distinguishing between Selective Sweeps from Standing Variation and from a De Novo Mutation , 2012, PLoS genetics.

[2]  J. Marchini,et al.  Multiway Admixture Deconvolution Using Phased or Unphased Ancestral Panels , 2013, Genetic epidemiology.

[3]  B. Weir,et al.  ESTIMATING F‐STATISTICS FOR THE ANALYSIS OF POPULATION STRUCTURE , 1984, Evolution; international journal of organic evolution.

[4]  David Reich,et al.  Combining evidence of natural selection with association analysis increases power to detect malaria-resistance variants. , 2007, American journal of human genetics.

[5]  D. Reich,et al.  The landscape of Neandertal ancestry in present-day humans , 2014, Nature.

[6]  Yongtao Guan Detecting Structure of Haplotypes and Local Ancestry , 2014, Genetics.

[7]  Pardis C Sabeti,et al.  Genome-wide detection and characterization of positive selection in human populations , 2007, Nature.

[8]  J. Pritchard,et al.  Admixture facilitates genetic adaptations to high altitude in Tibet , 2014, Nature Communications.

[9]  D. Reich,et al.  Sensitive Detection of Chromosomal Segments of Distinct Ancestry in Admixed Populations , 2009, PLoS genetics.

[10]  C. Bustamante,et al.  RFMix: a discriminative modeling approach for rapid and robust local-ancestry inference. , 2013, American journal of human genetics.

[11]  M. Daly,et al.  Methods for high-density admixture mapping of disease genes. , 2004, American journal of human genetics.

[12]  P. Visscher,et al.  Geographical structure and differential natural selection among North European populations. , 2009, Genome research.

[13]  Xiaofeng Zhu,et al.  Genome-wide comparison of African-ancestry populations from CARe and other cohorts reveals signals of natural selection. , 2011, American journal of human genetics.

[14]  David Comas,et al.  Extreme Population Differences in the Human Zinc Transporter ZIP4 (SLC39A4) Are Explained by Positive Selection in Sub-Saharan Africa , 2014, PLoS genetics.

[15]  Xiaofeng Zhu,et al.  The landscape of recombination in African Americans , 2011, Nature.

[16]  Joseph K. Pickrell,et al.  Signals of recent positive selection in a worldwide sample of human populations. , 2009, Genome research.

[17]  Pardis C Sabeti,et al.  Positive Natural Selection in the Human Lineage , 2006, Science.

[18]  Y. Teo,et al.  Singapore Genome Variation Project: a haplotype map of three Southeast Asian populations. , 2009, Genome research.

[19]  Stephen L. Hauser,et al.  Genome-wide patterns of population structure and admixture in West Africans and African Americans , 2009, Proceedings of the National Academy of Sciences.

[20]  R. Lewontin,et al.  Distribution of gene frequency as a test of the theory of the selective neutrality of polymorphisms. , 1973, Genetics.

[21]  A. Price,et al.  New approaches to disease mapping in admixed populations , 2011, Nature Reviews Genetics.

[22]  N. Patterson,et al.  Estimating and interpreting FST: The impact of rare variants , 2013, Genome research.

[23]  J. Pritchard,et al.  A Map of Recent Positive Selection in the Human Genome , 2006, PLoS biology.

[24]  S. O’Brien,et al.  Mapping by admixture linkage disequilibrium: advances, limitations and guidelines , 2005, Nature Reviews Genetics.

[25]  Or Zuk,et al.  A Composite of Multiple Signals Distinguishes Causal Variants in Regions of Positive Selection , 2010, Science.

[26]  Yiping Shen,et al.  Genome-wide detection of natural selection in African Americans pre- and post-admixture. , 2012, Genome research.

[27]  Scott M. Williams,et al.  A high-density admixture map for disease gene discovery in african americans. , 2004, American journal of human genetics.

[28]  Asan,et al.  Altitude adaptation in Tibet caused by introgression of Denisovan-like DNA , 2014, Nature.

[29]  Joshua M. Akey,et al.  Resurrecting Surviving Neandertal Lineages from Modern Human Genomes , 2014, Science.

[30]  Pedro C. Avila,et al.  Analysis of Latino populations from GALA and MEC studies reveals genomic loci with biased local ancestry estimation , 2013, Bioinform..

[31]  B S Weir,et al.  Estimating F-statistics. , 2002, Annual review of genetics.

[32]  David Reich,et al.  Population differentiation as a test for selective sweeps. , 2010, Genome research.

[33]  M. Shriver,et al.  Interrogating a high-density SNP map for signatures of natural selection. , 2002, Genome research.

[34]  Luca Pagani,et al.  Genetic Signatures Reveal High-Altitude Adaptation in a Set of Ethiopian Populations , 2013, Molecular biology and evolution.

[35]  Pedro C. Avila,et al.  Fast and accurate inference of local ancestry in Latino populations , 2012, Bioinform..

[36]  Ole A. Andreassen,et al.  The Impact of Divergence Time on the Nature of Population Structure: An Example from Iceland , 2009, PLoS genetics.

[37]  Dianne J Terlouw,et al.  Protective effects of the sickle cell gene against malaria morbidity and mortality , 2002, The Lancet.

[38]  Joshua M Akey,et al.  Where do we go from here? Constructing genomic maps of positive selection in humans: , 2009 .

[39]  Kenny Q. Ye,et al.  An integrated map of genetic variation from 1,092 human genomes , 2012, Nature.

[40]  Benjamin A. Logsdon,et al.  Imputation of exome sequence variants into population- based samples and blood-cell-trait-associated loci in African Americans: NHLBI GO Exome Sequencing Project. , 2012, American journal of human genetics.

[41]  M. Slatkin,et al.  Estimation of levels of gene flow from DNA sequence data. , 1992, Genetics.