TY  - JOUR
A1  - Li, Chen
A1  - Stoma, Svetlana
A1  - Lotta, Luca A.
A1  - Warner, Sophie
A1  - Albrecht, Eva
A1  - Allione, Alessandra
A1  - Arp, Pascal P.
A1  - Broer, Linda
A1  - Buxton, Jessica L.
A1  - Boeing, Heiner
A1  - Langenberg, Claudia
A1  - Codd, Veryan
T1  - Genome-wide association analysis in humans links nucleotide metabolism to leukocyte telomere length
JF  - American Journal of Human Genetics
N2  - Leukocyte telomere length (LTL) is a heritable biomarker of genomic aging. In this study, we perform a genome-wide meta-analysis of LTL by pooling densely genotyped and imputed association results across large-scale European-descent studies including up to 78,592 individuals. We identify 49 genomic regions at a false dicovery rate (FDR) < 0.05 threshold and prioritize genes at 31, with five highlighting nucleotide metabolism as an important regulator of LTL. We report six genome-wide significant loci in or near SENP7, MOB1B, CARMIL1 , PRRC2A, TERF2, and RFWD3, and our results support recently identified PARP1, POT1, ATM, and MPHOSPH6 loci. Phenome-wide analyses in >350,000 UK Biobank participants suggest that genetically shorter telomere length increases the risk of hypothyroidism and decreases the risk of thyroid cancer, lymphoma, and a range of proliferative conditions. Our results replicate previously reported associations with increased risk of coronary artery disease and lower risk for multiple cancer types. Our findings substantially expand current knowledge on genes that regulate LTL and their impact on human health and disease.
KW  - Mendelian randomization
KW  - risk
KW  - variants
KW  - disease
KW  - cancer
KW  - loci
KW  - database
KW  - genes
KW  - heart
KW  - gwas
Y1  - 2019
VL  - 106
IS  - 3
PB  - Elsevier
CY  - Amsterdam
ER  - 
TY  - GEN
A1  - Li, Chen
A1  - Stoma, Svetlana
A1  - Lotta, Luca A.
A1  - Warner, Sophie
A1  - Albrecht, Eva
A1  - Allione, Alessandra
A1  - Arp, Pascal P.
A1  - Broer, Linda
A1  - Buxton, Jessica L.
A1  - Boeing, Heiner
A1  - Langenberg, Claudia
A1  - Codd, Veryan
T1  - Genome-wide association analysis in humans links nucleotide metabolism to leukocyte telomere length
T2  - Postprints der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe
N2  - Leukocyte telomere length (LTL) is a heritable biomarker of genomic aging. In this study, we perform a genome-wide meta-analysis of LTL by pooling densely genotyped and imputed association results across large-scale European-descent studies including up to 78,592 individuals. We identify 49 genomic regions at a false dicovery rate (FDR) < 0.05 threshold and prioritize genes at 31, with five highlighting nucleotide metabolism as an important regulator of LTL. We report six genome-wide significant loci in or near SENP7, MOB1B, CARMIL1 , PRRC2A, TERF2, and RFWD3, and our results support recently identified PARP1, POT1, ATM, and MPHOSPH6 loci. Phenome-wide analyses in >350,000 UK Biobank participants suggest that genetically shorter telomere length increases the risk of hypothyroidism and decreases the risk of thyroid cancer, lymphoma, and a range of proliferative conditions. Our results replicate previously reported associations with increased risk of coronary artery disease and lower risk for multiple cancer types. Our findings substantially expand current knowledge on genes that regulate LTL and their impact on human health and disease.
T3  - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 1205 
KW  - Mendelian randomization
KW  - risk
KW  - variants
KW  - disease
KW  - cancer
KW  - loci
KW  - database
KW  - genes
KW  - heart
KW  - gwas
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-526843
SN  - 1866-8372
IS  - 3
ER  -