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There is substantial genetic variation for drought adaption in pearl millet in terms of traits controlling plant water use. It is important to understand genomic regions responsible for these traits. Here, F7 recombinant inbred lines were used to identify quantitative trait loci ( QTL) and allelic interactions for traits affecting plant water use, and their relevance is discussed for crop productivity in water-limited environments. Four QTL contributed to increased transpiration rate under high vapour pressure deficit ( VPD) conditions, all with alleles from drought-sensitive parent ICMB 841. Of these four QTL, a major QTL (35.7%) was mapped on linkage group ( LG) 6. The alleles for 863B at this QTL decreased transpiration rate and this QTL co-mapped to a previously detected LG 6 QTL, with alleles from 863B for grain weight and panicle harvest index across severe terminal drought stress environments. This provided additional support for a link between water saving from a lower transpiration rate under high VPD and drought tolerance. 863B alleles in this same genomic region also increased shoot weight, leaf area and total transpiration under well-watered conditions. One unexpected outcome was reduced transpiration under high VPD (15%) from the interaction of two alleles for high VPD transpiration ( LG 6 (B), 40.7) and specific leaf mass and biomass ( LG 7 (A), 35.3), (A, allele from ICMB 841, B, allele from 863B, marker position). The LG 6 QTL appears to combine alleles for growth potential, beneficial for non-stress conditions, and for saving water under high evaporative demand, beneficial under stressful conditions. Mapping QTL for water-use traits, and assessing their interactions offers considerable potential for improving pearl millet adaptation to specific stress conditions through physiology-informed marker-assisted selection. [ABSTRACT FROM AUTHOR]