SNP rs6543176 is associated with extreme human longevity but increased risk for cancer

Anastasia Gurinovich; Zeyuan Song; Harold Bae; Anastasia Leshchyk; Mengze Li; Hannah Lords; Stacy L Andersen; Marianne Nygaard; Kaare Christensen; E Warwick Daw; Konstantin G Arbeev; Michael R Brent; Thomas T Perls; Paola Sebastiani

doi:10.1007/s11357-024-01478-5

SNP rs6543176 is associated with extreme human longevity but increased risk for cancer

Geroscience. 2025 Jan 3. doi: 10.1007/s11357-024-01478-5. Online ahead of print.

Authors

Anastasia Gurinovich^{1

2}, Zeyuan Song^{3

4}, Harold Bae⁵, Anastasia Leshchyk^{6

7}, Mengze Li^{6

7}, Hannah Lords^{6

7}, Stacy L Andersen⁸, Marianne Nygaard⁹, Kaare Christensen^{9

10

11}, E Warwick Daw¹², Konstantin G Arbeev¹³, Michael R Brent¹⁴, Thomas T Perls⁸, Paola Sebastiani^{3

4

15}

Affiliations

¹ Institute for Clinical Research and Health Policy Studies, Tufts Medical Center, Boston, MA, 02111, USA. [email protected].
² Department of Medicine, Tufts University, Boston, MA, 02111, USA. [email protected].
³ Institute for Clinical Research and Health Policy Studies, Tufts Medical Center, Boston, MA, 02111, USA.
⁴ Department of Medicine, Tufts University, Boston, MA, 02111, USA.
⁵ Biostatistics Program, College of Health, Oregon State University, Corvallis, OR, 97331, USA.
⁶ Bioinformatics Program, Faculty of Computing & Data Sciences, Boston University, Boston, MA, 02215, USA.
⁷ Department of Medicine, Computational Biomedicine Section, School of Medicine, Boston University, Chobanian & Avedisian, Boston, MA, 02118, USA.
⁸ Department of Medicine, Section of Geriatrics, School of Medicine, Boston University, Chobanian & Avedisian, Boston, MA, 02118, USA.
⁹ Epidemiology, Biostatistics and Biodemography, Department of Public Health, University of Southern Denmark, Odense, Denmark.
¹⁰ Department of Clinical Genetics, Odense University Hospital, Odense, Denmark.
¹¹ Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, Odense, Denmark.
¹² Division of Statistical Genomics, Washington University in St. Louis, St. Louis, MO, 63130, USA.
¹³ Biodemography of Aging Research Unit, Social Science Research Institute, Duke University, Durham, NC, 27708, USA.
¹⁴ Division of Computational and Data Sciences, Center for Genome Sciences and Systems Biology, Washington University in St. Louis, St. Louis, MO, 63130, USA.
¹⁵ Data Intensive Study Center, Tufts University, Medford, MA, 02155, USA.

PMID: 39751714
DOI: 10.1007/s11357-024-01478-5

Abstract

Using whole-genome sequencing (WGS) might offer insights into rare genetic variants associated with healthy aging and extreme longevity (EL), potentially pointing to useful therapeutic targets. In this study, we conducted a genome-wide association study using WGS data from the Long Life Family Study and identified a novel longevity-associated variant rs6543176 in the SLC9A2 gene. This SNP also showed a significant association with reduced hypertension risk and an increased, though not statistically significant, cancer risk. The association with cancer risk was replicated in the UK Biobank and FinnGen. Metabolomic analyses linked the rs6543176 longevity allele to higher serine levels, potentially associated with delayed mortality. Our findings warrant further investigation of SLC9A2's role in both longevity and cancer susceptibility, and they highlight the need for careful evaluation in developing anti-aging therapies based on EL-associated alleles.

Keywords: Cancer; Extreme Longevity; rs6543176.

Abstract

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