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Genetic factors underlying leukocyte telomere length (LTL) may provide insights into telomere homeostasis, with direct links to disease susceptibility. Genetic evaluation of 23,096 Singaporean Chinese samples identifies 10 genome-wide loci ( P  < 5 × 10 −8 ). Several of these contain candidate genes ( TINF2 ,  PARP1 ,  TERF1 ,  ATM  and  POT1 ) with potential roles in telomere biology and DNA repair mechanisms. Meta-analyses with additional 37,505 European individuals reveals six more genome-wide loci, including associations at  MPHOSPH6 ,  NKX2-3  and  TYMS . We demonstrate that longer LTL associates with protection against respiratory disease mortality [HR = 0.854(0.804–0.906),  P  = 1.88 × 10 −7 ] in the Singaporean Chinese samples. We further show that the LTL reducing SNP rs7253490 associates with respiratory infections ( P  = 7.44 × 10 −4 ) although this effect may not be strongly mediated through LTL. Our data expands on the genetic basis of LTL and may indicate on a potential role of LTL in immune competence.

Loci for human leukocyte telomere length in the Singaporean Chinese population and trans-ethnic genetic studies