ABSTRACT: As an important functional organ of plants, leaves alter their shapes in response to a changing environment. The variation of leaf shape has long been an important evolutionary and developmental force in plants. Despite an increasing amount of investigations into the genetic controls of leaf morphology, few have systematically studied the genetic architecture controlling shape differences among distinct altitudes. Altitude denotes a comprehensive complex of environmental factors affecting plant growth in many aspects, e.g., UV-light radiation, temperature, and humidity. To reveal how plants alter ecological adaptation to altitude through genes, we used Populus szechuanica var. tibetica growing on the Qinghai-Tibetan plateau. F ST between the low- and high- altitude population was 0.00748, Q ST for leaf width, length and area were 0.00924, 0.1108, 0.00964 respectively. With the Elliptic Fourier-based morphometric model, association study of leaf shape was allowed, the dissection of the pleiotropic expression of genes mediating altitude-derived leaf shape variation was performed. For high and low altitudes, 130 and 131 significant single-nucleotide polymorphisms (SNPs) were identified. QTLs that affected leaf axis length and leaf width were expressed in both-altitude population, while QTLs regulating "leaf tip" and "leaf base" were expressed in low-altitude population. Pkinase and PRR2 were common significant genes in both types of populations. Auxin-related and differentiation-related genes included PIN1, CDK-like, and CAK1AT at high altitude, whereas they included NAP5, PIN-LIKES, and SCL1 at low altitude. The presence of Stress-antifung gene, CIPK3 and CRPK1 in high-altitude population suggested an interaction between genes and harsh environment in mediating leaf shape, while the senescence repression-related genes (EIN2 and JMJ18) and JMT in jasmonic acid pathway in low-altitude population suggested their crucial roles in ecological adaptability. These data provide new information that strengthens the understanding of genetic control with respect to leaf shape and constitute an entirely novel perspective regarding leaf adaptation and development in plants.