equilibrium and the frequency for rs2866164-G is similar in the middle-aged and nonagenarian groups, with no statistically significant difference. The frequency for the suggested risk haplotype is also not significantly different between the two age cohorts. In the survival analysis, we found no significant association between the risk haplotype and mortality in nonagenarians after 6.5 years of follow-up. Additionally, the younger control group showed no significant differences in allele frequencies compared to the nonagenarians. Our study provides no support for an association between Microsomal Transfer Protein gene and extreme longevity in a genetically homogeneous population.Equilibrium was observed for both SNPs and haplotypes in both age groups (PZ0.29). None of the prevalence differences of the suggested risk alleles (rs2866164-G and MTP Q95) and the combined risk haplotype were significant at a 0.05 level (Tables 13). Furthermore, there was no statistically significant difference in distribution between the subjects from the 1905 cohort who were alive at the last follow-up in January 2005 (6.5 years after recruitment) and those who died before January 2005. Shown are counts (frequencies) for rs2866164 and MTP Q/H.

SNP         Middle-aged     1905-cohort Survivors
            1905            rs 2866164-C    442 (77.0%)    1727 (73.9%)    322 (72.9%)
            rs 2866164-G    132 (23.0%)    609 (26.1%)    120 (27.1%)
            MTP Q95         546 (95.1%)    2236 (95.7%)   423 (95.7%)
            MTP H95         28 (4.9%)      100 (4.3%)     19 (4.3%)

1.00    0.75    0.50    0.25    0.00
0       500     1000    1500    2000
2500 analysis time
haplotype = 11 haplotype = 12 haplotype =22

Shown are counts (frequencies) for rs2866164 and MTP Q/H.

Discussion

In contrast with the previous publication in PNAS by Geesaman et al, our data fail to provide evidence for a role for MTP in human longevity. There is no increased mortality among carriers of the risk haplotype composed of the rs2866164-G and the Q95 allele in the longitudinal study of 1651 nonagenarians. Furthermore, there is no significant difference between the distribution of the two SNPs and the risk haplotype in the two tested age cohorts. The paper by Geesaman et al included a confirmatory study of a French centenarian cohort compared to younger French controls. There was no significant difference in allele frequencies with respect to the risk haplotype. However, the risk haplotype was found to be out of Hardy-Weinberg equilibrium with the other haplotypes in the centenarians, but not in the controls. We find frequencies in our middle-aged population very close to those of the French control group - the frequency is 24.1% for rs2866164-G compared to 26.4% in the French population, and for the risk haplotype, the frequency is 20.1% compared to 19.6%. The risk haplotype is in Hardy-Weinberg equilibrium in our cohorts for both individual SNPs and combined haplotypes.

Our population is slightly younger than that of Geesaman et al. Their long-lived individuals had a mean age of 100.8 years. Participants in our study population were 92-93 years when they entered the study and 99 years at the end of follow-up - and intuitively this seems to be an already much-selected population, close to becoming centenarians. However, being 92-93 is only halfway to becoming a centenarian in terms of selection: only about one in 20 of the 1905 cohort made it to age 92-93, but it is also only about one in 20 of these survivors to age 92-93 who will celebrate a 100-year birthday. Hence, the Danish 1905 cohort provides a powerful opportunity to test for selection against a genotype marker, and even though our cases are slightly younger, this large study of 1651 subjects aged 92-93 years should be able to detect a significant difference. As can be seen from Figures 1 and 2, there is no significant survival difference between those carrying the suggested risk allele and those without this allele. In males, there is even a small, not significant tendency towards better survival of those homozygous for the suggested risk allele.

One explanation for the discrepancy between the study by Geesaman et al and our data could be that the American population is less homogeneous than ours. A major problem in genetic association studies is the failure to adequately match the genetic backgrounds of cases and controls, and in the study of Geesaman et al, the cases and controls were born more than 50 years apart. The Danish population is known to be genetically and ethnically very homogeneous and therefore well-suited for association studies in different age groups. The middle-aged twins were born and grew upAs an AI language model, I cannot identify any text to proofread or improve in the statement "909920." Please provide me with the text to work on.