Chronic kidney disease (CKD) is a common but frequently unrecognized medical condition that is associated with high morbidity and mortality. Presence of CKD is defined by low estimated glomerular filtration rate (eGFR), a heritable measure of kidney function. To identify genetic loci for eGFR, we conducted whole genome sequencing analysis of 23,732 participants of 10 multi-ethnic (European, African, East Asian, and Hispanic) cohort studies within the NHLBI TOPMed Project. An extensive, centralized quality control was performed in the sequencing data. Calibrated serum creatinine was used to estimate eGFR, which was inverse normalized within study and ethnic groups and rescaled to recover original trait variances. We applied linear mixed models adjusted for age, sex, study, and ethnicity; the variance components were modeled by the genetic relationship matrix estimated from the whole genome sequencing data. In single-variant tests with minor allele counts > 10, there was no evidence of inflation (lambda=1.009). Four loci were significantly associated with eGFR at the genome-wide significance threshold of P=5.0 x 10-9, including three novel loci (NBPF7, rs184708696, MAF 0.04%, P=2.95 x 10-9; BOLL, rs375059924, MAF 0.07%, P=4.57 x 10-10; and FAM46A, rs143018620, MAF 0.09%, P=2.13 x 10-9). At the FAM46A locus, the signal extended for 94.2 kb upstream of the gene and was comprised of several highly correlated low frequency variants present in individuals of East Asian ancestry (n=2,208). Compared to individuals with the rs143018620 reference allele, each additional copy of the minor allele increased eGFR by 8.9 ml/min/1.73m2 (standard error = 1.5 ml/min/1.73m2). Several signals that almost reached genome-wide significance were located in known eGFR loci, including GATM, GCKR, BCAS3, and PDILT/UMOD. Gene-based burden tests of loss of function variants with MAF<1% did not reach genome-wide significance. In conclusion, analyses of deep sequenced TOPMed whole genome sequencing in multi-ethnic studies have identified three novel genome-wide significant loci for eGFR, including a rare, long-range haplotype specific to East Asians that confers a protective effect for kidney function.