Genetic insights into number of long-term conditions and their relationship with lifespan.

A GWAS of LTC burden identified 21 significant independent loci, with loci in the HLA region being the most significant.

• The GWAS was conducted on 343,868 UK Biobank individuals.
• 21 significant independent loci were identified across the genome.
• Loci in the HLA (Human Leukocyte Antigen) region were the most significant among all identified loci.

LTC burden has a statistically significant SNP heritability of approximately 9.6%.

• The estimated SNP heritability of LTC burden was 0.0963.
• Standard error was 0.0034.
• The heritability estimate was significantly different from zero (p-value = 1.77 x 10-176).

LTC burden and parental lifespan exhibited a significant and strong negative global genetic correlation.

• The global genetic correlation between LTC burden and parental lifespan was -0.7869 (se = 0.0419).
• This correlation was statistically significant (p-value = 9.57 x 10-79).
• The negative correlation indicates that genetic factors increasing LTC burden are associated with shorter parental lifespan.

Forty-four loci showed significant local genetic correlations between LTC burden and parental lifespan.

• 44 loci showed significant local genetic correlations at a threshold of p-value < 2.23 x 10-5.
• Local genetic correlations provide finer-grained regional insights beyond the global genetic correlation estimate.

Individuals in the highest 10% of polygenic risk score for LTC burden had shorter lifespans and more long-term conditions than those in the lowest 10%.

• The polygenic risk score (PRSLTC) was derived from a separate set of 34,339 UK Biobank individuals with records of age at death, who were not included in the GWAS analysis.
• Individuals in the highest 10% PRSLTC had, on average, a 0.9-year shorter lifespan than those in the lowest 10%.
• Individuals in the highest 10% PRSLTC had, on average, 0.73 more LTCs than those in the lowest 10%.