Investigating Direct and Indirect Genetic Effects in Attention-Deficit/Hyperactivity Disorder Using Parent-Offspring Trios.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is highly heritable, but little is known about the relative effects of transmitted (i.e., direct) and nontransmitted (i.e., indirect) common variant risks. Using parent-offspring trios, we tested whether polygenic liability for neurodevelopmental and psychiatric disorders and lower cognitive ability is overtransmitted to ADHD probands. We also tested for indirect or genetic nurture effects by examining whether nontransmitted ADHD polygenic liability is elevated. Finally, we examined whether complete trios are representative of the clinical ADHD population. METHODS: Polygenic risk scores (PRSs) for ADHD, anxiety, autism, bipolar disorder, depression, obsessive-compulsive disorder, schizophrenia, Tourette syndrome, and cognitive ability were calculated in UK control subjects (n = 5081), UK probands with ADHD (n = 857), their biological parents (n = 328 trios), and also a replication sample of 844 ADHD trios. RESULTS: ADHD PRSs were overtransmitted and cognitive ability and obsessive-compulsive disorder PRSs were undertransmitted. These results were independently replicated. Overtransmission of polygenic liability was not observed for other disorders. Nontransmitted alleles were not enriched for ADHD liability compared with control subjects. Probands from incomplete trios had more hyperactive-impulsive and conduct disorder symptoms, lower IQ, and lower socioeconomic status than complete trios. PRS did not vary by trio status. CONCLUSIONS: The results support direct transmission of polygenic liability for ADHD and cognitive ability from parents to offspring, but not for other neurodevelopmental/psychiatric disorders. They also suggest that nontransmitted neurodevelopmental/psychiatric parental alleles do not contribute indirectly to ADHD via genetic nurture. Furthermore, ascertainment of complete ADHD trios may be nonrandom, in terms of demographic and clinical factors.

Routine use of both mammography and MRI surveillance in patients with previous 'mammogram occult' breast cancer: experience from a tertiary centre.

BACKGROUND: To evaluate the role of combined MRI and mammogram follow-up in patients with previous 'mammographically occult' breast cancer. METHODS: Between 2011 and 2016, examinations of all patients undergoing routine surveillance following previous 'mammogram occult' breast cancer were evaluated. Patients had both MRI and mammograms on the same day with an interval of 12-18 months between consecutive pairs. Total number of recalls on both imaging modalities and the outcome of those recalls was recorded. There were six median examinations per patient. RESULTS: There were a total of 325 examinations of 54 patients. There were 96 mammograms/MRI pairs and 87 lone MRI and 46 lone mammograms. There were a total of 26 recalls in 21 patients. MRI had specificity (95% CI) of 89.99 (85.67 to 93.11) compared to mammograms 96.27 (92.53 to 98.25). The diagnostic OR with 95% CI was 19.40 (3.70 to 101.57) vs 6.72 (1.43 to 31.58) of mammograms and MRI, respectively. Three of seven cancers presented symptomatically. CONCLUSIONS: MRI surveillance leads to higher recalls and false positives compared to mammograms in this specific subgroup of high-risk patients. Large proportion of cancers presented symptomatically, stressing the importance of remaining vigilant of breast symptoms despite imaging surveillance.