@article{fdi:010052848, title = {{A}ssociation mapping of insecticide resistance in wild {A}nopheles gambiae populations : major variants identified in a low-linkage disequilbrium genome}, author = {{W}eetman, {D}. and {W}ilding, {C}. {S}. and {S}teen, {K}. and {M}organ, {J}. {C}. and {S}imard, {F}r{\'e}d{\'e}ric and {D}onnelly, {M}. {J}.}, editor = {}, language = {{ENG}}, abstract = {{B}ackground: {A}ssociation studies are a promising way to uncover the genetic basis of complex traits in wild populations. {D}ata on population stratification, linkage disequilibrium and distribution of variant effect-sizes for different trait-types are required to predict study success but are lacking for most taxa. {W}e quantified and investigated the impacts of these key variables in a large-scale association study of a strongly selected trait of medical importance: pyrethroid resistance in the {A}frican malaria vector {A}nopheles gambiae. {M}ethodology/{P}rincipal {F}indings: {W}e genotyped approximate to 1500 resistance-phenotyped wild mosquitoes from {G}hana and {C}ameroon using a 1536-{SNP} array enriched for candidate insecticide resistance gene {SNP}s. {T}hree factors greatly impacted study power. (1) {P}opulation stratification, which was attributable to co-occurrence of molecular forms ({M} and {S}), and cryptic within-form stratification necessitating both a partitioned analysis and genomic control. (2) {A}ll {SNP}s of substantial effect (odds ratio, {OR}. 2) were rare (minor allele frequency, {MAF}, 0.05). (3) {L}inkage disequilibrium ({LD}) was very low throughout most of the genome. {N}evertheless, locally high {LD}, consistent with a recent selective sweep, and uniformly high {OR}s in each subsample facilitated significant direct and indirect detection of the known insecticide target site mutation kdr {L}1014{F} ({OR}< 6; {P}, 10 26), but with resistance level modified by local haplotypic background. {C}onclusion: {P}rimarily as a result of very low {LD} in wild {A}. {G}ambiae, {LD}-based association mapping is challenging, but is feasible at least for major effect variants, especially where {LD} is enhanced by selective sweeps. {S}uch variants will be of greatest importance for predictive diagnostic screening.}, keywords = {}, booktitle = {}, journal = {{P}los {O}ne}, volume = {5}, numero = {10}, pages = {e13140}, ISSN = {1932-6203}, year = {2010}, DOI = {10.1371/journal.pone.0013140}, URL = {https://www.documentation.ird.fr/hor/fdi:010052848}, }