title: Mapping the genomic architecture of adaptive traits with interspecific introgressive origin: a coalescent-based approach.
abstract: Recent studies of eukaryotes including human and Neandertal, mice, and butterflies have highlighted the major role that interspecific introgression has played in adaptive trait evolution. A common question arises in each case: what is the genomic architecture of the introgressed traits? One common approach that can be used to address this question is association mapping, which looks for genotypic markers that have significant statistical association with a trait. It is well understood that sample relatedness can be a confounding factor in association mapping studies if not properly accounted for. Introgression and other evolutionary processes (e.g., incomplete lineage sorting) typically introduce variation among local genealogies, which can also differ from global sample structure measured across all genomic loci. In contrast, state-of-the-art association mapping methods assume fixed sample relatedness across the genome, which can lead to spurious inference. We therefore propose a new association mapping method called Coal-Map, which uses coalescent-based models to capture local genealogical variation alongside global sample structure. Using simulated and empirical data reflecting a range of evolutionary scenarios, we compare the performance of Coal-Map against EIGENSTRAT, a leading association mapping method in terms of its popularity, power, and type I error control. Our empirical data makes use of hundreds of mouse genomes for which adaptive interspecific introgression has recently been described. We found that Coal-Map's performance is comparable or better than EIGENSTRAT in terms of statistical power and false positive rate. Coal-Map's performance advantage was greatest on model conditions that most closely resembled empirically observed scenarios of adaptive introgression. These conditions had: (1) causal SNPs contained in one or a few introgressed genomic loci and (2) varying rates of gene flow - from high rates to very low rates where incomplete lineage sorting dominated as a primary cause of local genealogical variation.
authors.affiliation: Department of Computer Science and Engineering, Michigan State University, 428 S. Shaw Lane, East Lansing, 48824, MI, USA. kjl@msu.edu.
authors.forename: Hussein A
authors.initials: HA
authors.lastname: Hejase
authors.affiliation: Department of Computer Science and Engineering, Michigan State University, 428 S. Shaw Lane, East Lansing, 48824, MI, USA. kjl@msu.edu.
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Liu
mesh_terms: D000465:Algorithms; D000818:Animals; D002874:Chromosome Mapping; D056426:Genetic Loci; D016678:Genome; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D051379:Mice; D008957:Models, Genetic; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide
references.citation: Genome Res. 1999 Aug;9(8):720-31
references.pmid: 10447507
references.citation: Biometrics. 1999 Dec;55(4):997-1004
references.pmid: 11315092
references.citation: Bioinformatics. 2002 Feb;18(2):337-8
references.pmid: 11847089
references.citation: Nature. 2003 Dec 18;426(6968):789-96
references.pmid: 14685227
references.citation: Nature. 2004 Feb 5;427(6974):537-41
references.pmid: 14765194
references.citation: Nat Genet. 2004 May;36(5):512-7
references.pmid: 15052271
references.citation: Nat Rev Genet. 2005 Aug;6(8):623-32
references.pmid: 16012528
references.citation: PLoS Genet. 2005 Sep;1(3):e32
references.pmid: 16151517
references.citation: Nat Genet. 2006 Aug;38(8):904-9
references.pmid: 16862161
references.citation: PLoS Genet. 2007 Feb 23;3(2):e7
references.pmid: 17319744
references.citation: Am J Hum Genet. 2008 Feb;82(2):290-303
references.pmid: 18252211
references.citation: Genetics. 2008 Mar;178(3):1709-23
references.pmid: 18385116
references.citation: Science. 2008 Nov 7;322(5903):881-8
references.pmid: 18988837
references.citation: Genetics. 2009 Feb;181(2):747-53
references.pmid: 19064712
references.citation: Genetics. 2009 Sep;183(1):259-74
references.pmid: 19581452
references.citation: Genome Res. 2009 Sep;19(9):1655-64
references.pmid: 19648217
references.citation: Nat Methods. 2009 Sep;6(9):663-6
references.pmid: 19668205
references.citation: Bioinformatics. 2010 Mar 15;26(6):798-806
references.pmid: 20097913
references.citation: PLoS Genet. 2010 Feb 05;6(2):e1000794
references.pmid: 20140188
references.citation: PLoS Genet. 2010 Feb 05;6(2):e1000796
references.pmid: 20140239
references.citation: Nat Genet. 2010 Apr;42(4):348-54
references.pmid: 20208533
references.citation: Science. 2010 May 7;328(5979):710-722
references.pmid: 20448178
references.citation: Nat Rev Genet. 2010 Jul;11(7):459-63
references.pmid: 20548291
references.citation: Bioinformatics. 2010 Aug 15;26(16):2064-5
references.pmid: 20591904
references.citation: Nature. 2010 Dec 23;468(7327):1053-60
references.pmid: 21179161
references.citation: Mol Biol Evol. 2011 Aug;28(8):2239-52
references.pmid: 21325092
references.citation: PLoS Genet. 2011 Mar;7(3):e1001319
references.pmid: 21408205
references.citation: Heredity (Edinb). 2011 Oct;107(5):413-20
references.pmid: 21448230
references.citation: PLoS Genet. 2011 Apr;7(4):e1001371
references.pmid: 21541012
references.citation: Nat Genet. 2011 May 29;43(7):648-55
references.pmid: 21623374
references.citation: Nat Rev Genet. 2011 Jun 28;12(8):523-8
references.pmid: 21709689
references.citation: Curr Biol. 2011 Aug 9;21(15):1296-301
references.pmid: 21782438
references.citation: Nature. 2011 Sep 14;477(7364):289-94
references.pmid: 21921910
references.citation: PLoS Comput Biol. 2011 Dec;7(12):e1002325
references.pmid: 22216000
references.citation: Proc Natl Acad Sci U S A. 2012 Jan 24;109(4):1193-8
references.pmid: 22223662
references.citation: BMC Genomics. 2012 Jan 19;13:34
references.pmid: 22260749
references.citation: Mol Biol Evol. 2012 Aug;29(8):1917-32
references.pmid: 22422763
references.citation: PLoS Genet. 2012;8(4):e1002660
references.pmid: 22536161
references.citation: Nat Genet. 2012 Jun 17;44(7):821-4
references.pmid: 22706312
references.citation: Nature. 2012 Jul 5;487(7405):94-8
references.pmid: 22722851
references.citation: Trends Genet. 2012 Sep;28(9):421-6
references.pmid: 22818580
references.citation: PLoS Genet. 2012;8(8):e1002891
references.pmid: 22956910
references.citation: PLoS Genet. 2012;8(12):e1003125
references.pmid: 23284294
references.citation: Nat Rev Genet. 2013 Apr;14(4):300
references.pmid: 23438870
references.citation: Nat Rev Genet. 2013 Apr;14(4):300
references.pmid: 23438871
references.citation: Nat Rev Genet. 2013 Jun;14(6):404-14
references.pmid: 23657479
references.citation: Heredity (Edinb). 2014 Jan;112(1):79-88
references.pmid: 23759726
references.citation: Trends Ecol Evol. 2013 Dec;28(12):719-28
references.pmid: 24094331
references.citation: PLoS Comput Biol. 2014 Jun 12;10(6):e1003649
references.pmid: 24922281
references.citation: Genome Res. 2014 Sep;24(9):1550-7
references.pmid: 24963154
references.citation: Nature. 2014 Aug 14;512(7513):194-7
references.pmid: 25043035
references.citation: Proc Natl Acad Sci U S A. 2014 Nov 18;111(46):16448-53
references.pmid: 25368173
references.citation: Proc Natl Acad Sci U S A. 2015 Jan 6;112(1):196-201
references.pmid: 25512534
references.citation: ACM Int Conf Bioinform Comput Biol (2010). 2010 Aug;2010:43-52
references.pmid: 29152612
references.citation: Proc Natl Acad Sci U S A. 1988 Dec;85(23):9119-23
references.pmid: 3194414
references.citation: Biometrics. 1988 Sep;44(3):837-45
references.pmid: 3203132
references.citation: Genetics. 1985 Sep;111(1):147-64
references.pmid: 4029609
references.citation: Ann Hum Genet. 1969 Jul;33(1):23-9
references.pmid: 5821316
references.citation: Genetics. 1997 Feb;145(2):519-34
references.pmid: 9071604