Imperial College London


Faculty of MedicineSchool of Public Health

Reader in Cardiometabolic Disease Epidemiology



+44 (0)20 7594 3347a.dehghan CV




157Norfolk PlaceSt Mary's Campus






BibTex format

author = {Tin, A and Li, Y and Brody, JA and Nutile, T and Chu, AY and Huffman, JE and Yang, Q and Chen, M-H and Robinson-Cohen, C and Macé, A and Liu, J and Demirkan, A and Sorice, R and Sedaghat, S and Swen, M and Yu, B and Ghasemi, S and Teumer, A and Vollenweider, P and Ciullo, M and Li, M and Uitterlinden, AG and Kraaij, R and Amin, N and van, Rooij J and Kutalik, Z and Dehghan, A and McKnight, B and van, Duijn CM and Morrison, A and Psaty, BM and Boerwinkle, E and Fox, CS and Woodward, OM and Köttgen, A},
doi = {10.1038/s41467-018-06620-4},
journal = {Nature Communications},
title = {Large-scale whole-exome sequencing association studies identify rare functional variants influencing serum urate levels},
url = {},
volume = {9},
year = {2018}

RIS format (EndNote, RefMan)

AB - Elevated serum urate levels can cause gout, an excruciating disease with suboptimal treatment. Previous GWAS identified common variants with modest effects on serum urate. Here we report large-scale whole-exome sequencing association studies of serum urate and kidney function among ≤19,517 European ancestry and African-American individuals. We identify aggregate associations of low-frequency damaging variants in the urate transporters SLC22A12 (URAT1; p = 1.3 × 10-56) and SLC2A9 (p = 4.5 × 10-7). Gout risk in rare SLC22A12 variant carriers is halved (OR = 0.5, p = 4.9 × 10-3). Selected rare variants in SLC22A12 are validated in transport studies, confirming three as loss-of-function (R325W, R405C, and T467M) and illustrating the therapeutic potential of the new URAT1-blocker lesinurad. In SLC2A9, mapping of rare variants of large effects onto the predicted protein structure reveals new residues that may affect urate binding. These findings provide new insights into the genetic architecture of serum urate, and highlight molecular targets in SLC22A12 and SLC2A9 for lowering serum urate and preventing gout.
AU - Tin,A
AU - Li,Y
AU - Brody,JA
AU - Nutile,T
AU - Chu,AY
AU - Huffman,JE
AU - Yang,Q
AU - Chen,M-H
AU - Robinson-Cohen,C
AU - Macé,A
AU - Liu,J
AU - Demirkan,A
AU - Sorice,R
AU - Sedaghat,S
AU - Swen,M
AU - Yu,B
AU - Ghasemi,S
AU - Teumer,A
AU - Vollenweider,P
AU - Ciullo,M
AU - Li,M
AU - Uitterlinden,AG
AU - Kraaij,R
AU - Amin,N
AU - van,Rooij J
AU - Kutalik,Z
AU - Dehghan,A
AU - McKnight,B
AU - van,Duijn CM
AU - Morrison,A
AU - Psaty,BM
AU - Boerwinkle,E
AU - Fox,CS
AU - Woodward,OM
AU - Köttgen,A
DO - 10.1038/s41467-018-06620-4
PY - 2018///
SN - 2041-1723
TI - Large-scale whole-exome sequencing association studies identify rare functional variants influencing serum urate levels
T2 - Nature Communications
UR -
UR -
UR -
VL - 9
ER -