The contribution of hereditary factors to the causation of sporadic cancer is unclear. Studies of twins make it possible to estimate the overall contribution of inherited genes to the development of malignant diseases. We combined data on 44,788 pairs of twins listed in the Swedish, Danish, and Finnish twin registries in order to assess the risks of cancer at 28 anatomical sites for the twins of persons with cancer. Statistical modeling was used to estimate the relative importance of heritable and environmental factors in causing cancer at 11 of those sites. At least one cancer occurred in 10,803 persons among 9512 pairs of twins. An increased risk was found among the twins of affected persons for stomach, colorectal, lung, breast, and prostate cancer. Statistically significant effects of heritable factors were observed for prostate cancer (42 percent of the risk may be explained by heritable factors; 95 percent confidence interval, 29 to 50 percent), colorectal cancer (35 percent; 95 percent confidence interval, 10 to 48 percent), and breast cancer (27 percent; 95 percent confidence interval, 4 to 41 percent). Inherited genetic factors make a minor contribution to susceptibility to most types of neoplasms. This finding indicates that the environment has the principal role in causing sporadic cancer. The relatively large effect of heritability in cancer at a few sites (such as prostate and colorectal cancer) suggests major gaps in our knowledge of the genetics of cancer.

Autism spectrum disorder (ASD) affects almost 1% of all children born in the United States¹ and is defined as impairment in social interaction and communication and the presence of restricted interests and repetitive behaviors. Autistic disorder is the most profound form of ASD.¹

Prior genome-wide association studies (GWAS) of major depressive disorder (MDD) have met with limited success. We sought to increase statistical power to detect disease loci by conducting a GWAS mega-analysis for MDD. In the MDD discovery phase, we analyzed more than 1.2 million autosomal and X chromosome single-nucleotide polymorphisms (SNPs) in 18 759 independent and unrelated subjects of recent European ancestry (9240 MDD cases and 9519 controls). In the MDD replication phase, we evaluated 554 SNPs in independent samples (6783 MDD cases and 50 695 controls). We also conducted a cross-disorder meta-analysis using 819 autosomal SNPs with P<0.0001 for either MDD or the Psychiatric GWAS Consortium bipolar disorder (BIP) mega-analysis (9238 MDD cases/8039 controls and 6998 BIP cases/7775 controls). No SNPs achieved genome-wide significance in the MDD discovery phase, the MDD replication phase or in pre-planned secondary analyses (by sex, recurrent MDD, recurrent early-onset MDD, age of onset, pre-pubertal onset MDD or typical-like MDD from a latent class analyses of the MDD criteria). In the MDD-bipolar cross-disorder analysis, 15 SNPs exceeded genome-wide significance (P<5 × 10⁻⁸), and all were in a 248 kb interval of high LD on 3p21.1 (chr3:52 425 083–53 822 102, minimum P=5.9 × 10⁻⁹ at rs2535629). Although this is the largest genome-wide analysis of MDD yet conducted, its high prevalence means that the sample is still underpowered to detect genetic effects typical for complex traits. Therefore, we were unable to identify robust and replicable findings. We discuss what this means for genetic research for MDD. The 3p21.1 MDD-BIP finding should be interpreted with caution as the most significant SNP did not replicate in MDD samples, and genotyping in independent samples will be needed to resolve its status.