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Previous Mendelian randomization (MR) studies on 25-hydroxyvitamin D (25(OH)D) and cancer have typically adopted a handful of variants and found no relationship between 25(OH)D and cancer; however, issues of horizontal pleiotropy cannot be reliably addressed. Using a larger set of variants associated with 25(OH)D (74 SNPs, up from 6 previously), we perform a unified MR analysis to re-evaluate the relationship between 25(OH)D and ten cancers. Our findings are broadly consistent with previous MR studies indicating no relationship, apart from ovarian cancers (OR 0.89; 95% C.I: 0.82 to 0.96 per 1 SD change in 25(OH)D concentration) and basal cell carcinoma (OR 1.16; 95% C.I.: 1.04 to 1.28). However, after adjustment for pigmentation related variables in a multivariable MR framework, the BCC findings were attenuated. Here we report that lower 25(OH)D is unlikely to be a causal risk factor for most cancers, with our study providing more precise confidence intervals than previously possible., Studies of the genetic association between vitamin D and cancer risk have typically been underpowered. Here the authors analyse this using Mendelian Randomisation with more than 70 vitamin D variants obtained from the UK Biobank and large-scale data from various consortia, confirming null associations between vitamin D and most cancers.

One afternoon late in 1987, the year I began working with him, Luca Cavalli-Sforza called me into his office. Laid out on his desk was a pencil-drawn diagram consisting of two parts. On the left Cavalli-Sforza had redrawn a tree of relationships among human populations derived from genetic data. On the right he had summarized the relationships among languages spoken by each population. In great excitement Cavalli-Sforza pointed out the extent of the correspondence between the two sides of the diagram. With that diagram he sowed the seeds of a debate that continues today: to what extent do human genetic and linguistic patterns correspond, and how did any such correspondence arise?

Seventy-nine DNA polymorphisms from 57 loci (28 genes and 29 anonymous DNA segments) have been typed in eight human populations. Here we present allele frequencies for three populations (Japanese, New Guineans, and Australians) as well as revised frequencies for a Chinese sample: allele frequencies for five additional populations (Biaka and Mbuti Pygmies, Melanesians, Chinese, and Europeans) were described previously [Bowcock et al 1991a]. Evaluation of Hardy-Weinberg equilibrium for these polymorphisms suggested that the New Guinean sample may be from a highly substructured population. Average FST value for the 79 markers (polymorphisms) was 0.147 +/- 0.011 across the eight populations: Fst values for some markers changed dramatically with the addition of three populations--in particular, Australians and New Guineans. Average heterozygosity for eight populations was 0.307 +/- 0.014. Genetic distances indicated that the Australian sample may have some European ancestry. An average linkage tree inferred from these distances suggested that the first split of modern humans was between Africans and non-Africans, while the second major split was between Australians/New Guineans and all other non-Africans. The neighbor-joining tree also separated the African populations from all others. European polymorphism ascertainment bias and European admixture appear to have influenced both estimation of population heterozygosity and tree inference.

One hundred DNA polymorphisms from 73 loci (42 genes and 31 anonymous DNA segments) were investigated in five populations (Biaka and Mbuti Pygmies, Melanesians, Chinese and Caucasoids). Data for 47 polymorphisms, including 42 of those discussed here, were described previously [Bowcock et al 1987]. Here we report statistical quantities of genetic importance for each gene and population. The average FST for the 100 markers is 0.137 and the average heterozygosity is 0.325. When known genes and anonymous segments are compared there is no significant difference in the average FST values or in the average heterozygosities.