Inference on the Genetic Basis of Eye and Skin Color in an Admixed Population via Bayesian Linear Mixed Models

• Published in: Genetics (Austin) 2017-06, Vol.206 (2), p.1113-1126
• Main Authors: Lloyd-Jones, Luke R, Robinson, Matthew R, Moser, Gerhard, Zeng, Jian, Beleza, Sandra, Barsh, Gregory S, Tang, Hua, Visscher, Peter M
• Format: Article
• Language: English
• Subjects: Africa, Western; Animal models; Bayes Theorem; Bayesian analysis; Bolts; Color; Computer simulation; Datasets; Eye; Eyes & eyesight; Gene loci; Gene mapping; Genetic effects; Genetic markers; Genetics; Genetics, Population; Genome-wide association studies; Genome-Wide Association Study; Genomes; Genomics; Humans; Investigations; Markers; Mathematical models; Pigmentation; Pigments, Biological - genetics; Polymorphism, Single Nucleotide - genetics; Population; Population (statistical); Population structure; Population studies; Principal components analysis; Quantitative Trait Loci; Skin; Skin pigmentation; Skin Pigmentation - genetics
• ISSN: 1943-2631; 0016-6731; 1943-2631
• DOI: 10.1534/genetics.116.193383

Genetic association studies in admixed populations are underrepresented in the genomics literature, with a key concern for researchers being the adequate control of spurious associations due to population structure. Linear mixed models (LMMs) are well suited for genome-wide association studies (GWAS) because they account for both population stratification and cryptic relatedness and achieve increased statistical power by jointly modeling all genotyped markers. Additionally, Bayesian LMMs allow for more flexible assumptions about the underlying distribution of genetic effects, and can concurrently estimate the proportion of phenotypic variance explained by genetic markers. Using three recently published Bayesian LMMs, Bayes R, BSLMM, and BOLT-LMM, we investigate an existing data set on eye ( = 625) and skin ( = 684) color from Cape Verde, an island nation off West Africa that is home to individuals with a broad range of phenotypic values for eye and skin color due to the mix of West African and European ancestry. We use simulations to demonstrate the utility of Bayesian LMMs for mapping loci and studying the genetic architecture of quantitative traits in admixed populations. The Bayesian LMMs provide evidence for two new pigmentation loci: one for eye color ( ) and one for skin color ( ).