PPMI 2018 ANNUUAL INVESTIGATORS MEETING May 2-3

Enrollment of LRRK2 and GBA Genetic cohort Tatiana Foroud

How do we efficiently identify mutation carriers?

16,106 Consented 10,165 8,700 Counseled Kits Sent 1546 1,084 Previous Results 10,165 Kits Sent 8,700 Counseled 1546 Mutation Carriers

Observed mutations among the carriers Number LRRK2 (G2019S) 689 GBA (N370S*) 811 LRRK2 + GBA 46 Totals 1546 Referred to PPMI 1457* * 89 individuals not referred to PPMI for a variety of reasons (decline, ineligible, lost to follow-up)

participants Recruited? How were PPMI participants Recruited? *Pulled 4/26/18

Genetic Mutations Enrolled in PPMI LRRK2 GBA Cohort PD Cohort UN Registry PD Registry UN Het Wt 136 184 146 140 Hom 3 5 9 4 67 123 53 99 6 1 2 11 Totals 215 324 208 258 *Pulled 4/26/18

Mutations Enrolled IN PPMI LRRK2 GBA SNCA G2019S N370S G209A R1441G L483P or L444P I2020T 84GG  N1437H R463C R1441H R496H

Jenny Lola Jeanine Amanda Malia Susan Verbrugge Shukla Schulze Miller Rumbaugh Selby

Genetic Counseling Outcomes in the WRI PPMI Study

Previous Genetic Counseling Outcomes A post-session knowledge survey assessed participant understanding to measure the impact of genetic counseling Results showed a high level of knowledge (average score, 86.4%). Significance limited by our highly educated participants and the absence of a pretest To avoid overburdening participants with a pretest, the knowledge survey was replaced with a satisfaction survey Between April 30, 2014 and November 30, 2014, 650 participants were counseled about their LRRK2 G2019S test results and emailed the survey link. Of these, 354 (55.1%) returned a survey

Genetic Counseling Satisfaction Survey (GCSS)   Strongly disagree Disagree somewhat Uncertain Agree somewhat Agree strongly 1. My genetic counselor seemed to understand the stresses I was facing. 1 2 3 4 5 2. My genetic counselor helped me identify what I needed to know to make decisions about what would happen to me. 3. I felt better about my health after meeting with my genetic counselor. 4. The genetic counseling session was about the right length of time I needed. 5. My genetic counselor was truly concerned about my well-being. 6. The genetic counseling session was valuable to me.

Genetic Counseling Satisfaction Survey Scores GCSS score P value Total responders 27.0 (n=376) PD: Affected 25.0 (n=94) 0.0001 PD: Unaffected 27.8 (n=277) Gender: Male 27.3 (n=212) 0.30 Gender: Female 26.7 (n=164) Mutation: positive 25.9 (n=62) 0.0045 Mutation: negative 27.2 (n=314) Leah, I didn’t see the male/female data more mean scores or the p-values to include in the chart on the left. For the p values we want to know if scores between groups were significantly different (PD vs unaff, Male vs female, mut + vs mut -). Lola, I can get participant numbers from the other studies and put them in the chart on the right. I am pretty sure they are much smaller than ours. (maximum score 30)

GCSS survey responders similar to non-responders p value Total 374 (48.8%) 392 (51.2%) Mean age 64.8 63.2 p=0.01 Male (%) 162 (43.3) 173 (44.1) p=0.82 PD (%) 92 (24.9) 100 (26.0) p=0.11 Mutation + (%) 62 (16.6) 61 (15.6) p=0.15 LRRK2 + (%) 21 (33.9) 16 (26.2) p=0.61 GBA + (%) 41 (66.1) 45 (73.8) p=0.36 Family history of PD (%) 44 (11.9) 52 (13.5) p=0.51 Conclusions: The overall response rate was very good and consistent with our previous surveys- almost 50%! Responders were not different than non-responders (for Pd, gender, and mutation status) Leah; was the % of LRRK2 + people different in responders vs non responders? Same question for GBA +

GCSS scores in PPMI compared to other studies Study population GCSS score Standard deviation Sample size Parkinson disease 27.0 3.9 376 Cancer1 26.9 61 Prenatal2 27.7 3.1 129 Leah, I didn’t see the male/female data more mean scores or the p-values to include in the chart on the left. For the p values we want to know if scores between groups were significantly different (PD vs unaff, Male vs female, mut + vs mut -). Lola, I can get participant numbers from the other studies and put them in the chart on the right. I am pretty sure they are much smaller than ours. 1 Demarco et al. 2004 2 Tercyak et al. 2001

Mutation Positive Individuals Recruitment of Mutation Positive Individuals PPMI has developed efficient approaches to screen and identify mutation position individuals Telephone genetic counseling has been effective This approach could be used for other studies and other disorders